Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

[McArdle's disease revealed by acute low back pain]. / Une maladie de McArdle révélée par une lombalgie aiguë.

INTRODUCTION: McArdle disease, or glycogen storage disease type V (GSD 5), is a rare metabolic myopathy linked to an autosomal recessive myophosphorylase deficiency. CASE REPORT: We report the case of a 17-year-old male patient who was referred to the emergency department for the management of acute inflammatory low back pain, without traumatic context, associated with an increase of CK at 66,336 UI/L (N<192UI/L) and a CRP at 202mg/L. The immunological assessment was negative and the spinal MRI showed images in favor of necrotizing fasciitis affecting the erector spinae muscles, among others. Faced with the description of difficulties in practicing physical activities since childhood and a non-ischaemic forearm exercise test showing no elevation in lactacidemia, genetic tests were carried out, finding two heterozygous variants in the PYGM gene: c.1963G>A (p.Glu655Lys) class 5 and c.2178-1G>A class 4, confirming the diagnosis of McArdle disease. DISCUSSION: GSD 5 is a disease characterized essentially by muscular fatigability during exercise. The case reported here is original in the clinical circumstances leading to the diagnosis, i.e., inaugural acute low back pain with rhabdomyolysis. This symptomatology had already been described before, but in a patient whose diagnosis was already known. Spinal MRI showed non-specific muscle inflammation and necrosis. Muscle biopsy only found necrosis but no pathological elements typical of the diagnosis. If the symptoms are suggestive, it may be preferable to directly perform a non-ischaemic forearm exercise test, in order to go directly to molecular genetic analysis. There is no specific curative treatment of GSD 5. However, some measures can be implemented to limit the symptoms, such as learning physical exercises, limiting intense efforts and adopting dietary recommendations.

[High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China].

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

[Establishment of the quality management system for occupational diseases diagnosis].

The quality management system of occupational diseases diagnosis is belonged to one part of the hospital quality management system. It must be adhered to the quality management concept of comprehensive, full staff and whole process. To establish and improve the quality management system should be included: (1) Formulated a quality management manual for occupational disease diagnosis, including organization construction, rules and regulations, responsibilities, work flow, operating procedures and clinical pathways, standard instrument, etc. (2) Managed the document of occupational diseases diagnosis. (3) The continuous improvement of quality management. The quality management of occupational diseases diagnosis focuses on the mastery and implementation of the manual by employees, which is reflected in the continuous improvement of daily work, internal assessment and external assessment.

[Practice and development of schistosomiasis control culture in China: A case of Jiangxi Province].

Schistosomiasis control is not only a disease control programme, but also a great social practice activity in China. During the evolution of national schistosomiasis control programmes, the special schistosomiasis control culture has been cultivated and developed, which contains the spiritual connotation of government-led, people-oriented, respect for science and integration of all efforts. The publication of Chairman Mao Zedong's two poems entitled "Farewell to the God of Plague" and the post-script in 1958 was a sign for the formation and development of Chinese schistosomiasis control culture, which always lead the orientation of development and practice of schistosomiasis control culture building. The schistosomiasis control culture provides powerful spiritual motivation and supports to schistosomiasis control programmes in China, and improving the building of schistosomiasis control culture is of great significance to strengthen our belief in achieving the goal of schistosomiasis elimination, mobilize all social resources, accelerate the progress towards elimination of schistosomiasis and facilitate the high-quality development of healthcare services. Chinese schistosomiasis control spirit is the refinement from the cultural connotation of the long-term schistosomiasis control programmes in China, and is the most essential and concentrated embodiment of the schistosomiasis control culture. This article describes the great significance of two poems entitled "Farewell to the God of Plague", summarizes the connotation and role of schistosomiasis control spirit, and introduces the practice, development and innovation of schistosomiasis control culture building in Jiangxi Province.

[Advances of pathological diagnosis and molecular pathology of lung neuroendocrine neoplasms].

The pathological classification and diagnostic criteria for lung neuroendocrine neoplasms (NENs) in the 2021 World Health Organization (WHO) lung tumor classification are similar to the prior classifications. However, the advances on the molecular studies of lung NENs have shown that both small cell lung carcinoma and large cell neuroendocrine carcinoma are highly heterogeneous tumors with neuroendocrine characteristics and can be subclassified based on the features of genomics or transcriptomics, which are valuable in the diagnosis of lung NENs subtypes and patient treatment. In addition, it is necessary to interpret emerging concepts such as "lung neuroendocrine tumor G3" and "histological transformation" from pathological perspectives, as well as to know the novel neuroendocrine biomarkers such as INSM1 and POU2F3. This article summarized the diagnostic changes and the advances of molecular pathology of lung NENs based on the latest WHO classification and molecular research.

Search for Evidence of Baryogenesis and Dark Matter in B

A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at 10.58 GeV, using data collected in the BABAR experiment. Data corresponding to an integrated luminosity of 398 fb^{-1} are analyzed. No evidence for a signal is observed. Branching fraction upper limits in the range from 10^{-7}-10^{-5} are obtained at 90% confidence level for masses of 1.0

[Analysis on the efficacy of dual vein induction therapy of Ustekinumab in complex perianal fistulizing Crohn's disease].

Objectives: To analyze the efficacy of dual vein induction therapy of Ustekinumab (UST) in complex perianal fistulizing Crohn's disease (PFCD). Methods: Clinical data of patients diagnosed with complex PFCD in the Second Affiliated Hospital of Wenzhou Medical University from January 2022 to March 2023 were retrospectively analyzed. After sufficient single intravenous infusion of UST (6 mg/kg) at week 0 and 8, every patient received single subcutaneous injection of UST 90 mg every 8 weeks for maintenance treatment. At week 8, 16, and 22-26, clinical outcomes of anal fistula were evaluated using perianal disease activity index (PDAI), and overall activity of the patients was evaluated using Harvey Bradshaw index (HBI). At week 22-26, Van Assche Index (VAI) was used to evaluate imaging outcome of anal fistula, and simplified endoscopic score of Crohn's disease (SES-CD) was employed to assess intestinal outcome events. The above indexes were compared in the patients before and after UST treatment. PFCD patients were divided into first-line UST treatment group and non first-line UST treatment group according to whether first-line UST treatment was used, the differences in anal fistula response rate and remission rate, intestinal response rate and remission rate as well as overall activity response rate and remission rate were compared between the two groups. Results: A total of 60 PFCD patients were included, including 46 males and 14 females, aged [M (Q1, Q3)] 25.0 (20.8, 30.0) years old. The clinical response rates of anal fistula [41.7% (25/60), 55.0% (33/60) and 63.3% (38/60), respectively, P=0.056] and the clinical remission rates of anal fistula [21.7% (13/60), 31.7% (19/60) and 43.3% (26/60), respectively, P=0.002] gradually increased at week 8, 16, 22-26. The overall activity response rates [53.3% (32/60), 70.0% (42/60), 83.3% (50/60), respectively, P=0.040] and the overall activity response rates [41.7% (25/60), 61.7% (37/60), 75.0% (45/60), respectively, P=0.001] also gradually increased at week 8, 16, 22-26. At week 22-26, the partial response rate and fistula healing rate of anal fistula imaging were 45.0% (27/60) and 38.3% (23/60), respectively. The endoscopic response rate and endoscopic response rate were 73.7% (44/60) and 45.0% (27/60), respectively. The endoscopic response rate of patients receiving first-line UST treatment [23 males and 8 females, aged 22.0 (21.0, 39.0) years] was higher than that of patients receiving non first-line UST treatment[23 males and 6 females, aged 26.5 (20.0, 30.0) years,87.1% vs 58.6%, P=0.013]. Conclusion: The dual vein induction therapy of UST could effectively improve the clinical efficacy in patients with complex PFCD.

HPV-positive clinically advanced squamous cell carcinoma of the urinary bladder (aBSCC): A comprehensive genomic profiling (CGP) study.

BACKGROUND: Advanced bladder squamous cell carcinoma (aBSCC) is an uncommon form of urinary bladder malignancy when compared with the much higher urothelial carcinoma incidence. We studied the genomic alteration (GA) landscape in a series of aBSCC based on the association with human papilloma virus (HPV) to determine if differences in GA would be observed between the positive and negative groups. METHODS: Using a hybrid capture-based FDA-approved CGP assay, a series of 171 aBSCC were sequenced to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. Programmed cell death ligand -1 (PD-L1) expression was determined by IHC (Dako 22C3) with negative expression when PD-L1 was 0, lower expression of positivity set at 1 to 49%, and higher expression set at ≥50% expression. RESULTS: Overall, 11 (6.4%) of the aBSCC were found to harbor HPV sequences (10 HPV16 and 1 HPV 11). HPV+ status was identified slightly more often in women (NS) and in younger patients (P = 0.04); 2 female patients with aBSCC had a prior history of SCC including 1 anal SCC and 1 vaginal SCC. HPV+ aBSCC had fewer GA/tumor (P < 0.0001), more inactivating mutations in RB1 (P = 0.032), and fewer inactivating GA in CDKN2A (P < 0.0001), CDKN2B (P = 0.05), TERT promoter (P = 0.0004) and TP53 (P < 0.0001). GA in genes associated with urothelial carcinoma including FGFR2 and FGFR3 were similar in both HPV+ and HPV- aBSCC groups. MTAP loss (homozygous deletion) which has emerged as a biomarker for PRMT5 inhibitor-based clinical trials was not identified in any of the 11 HPV+ aBSCC cases, which was significantly lower than the 28% positive frequency of MTAP loss in the HPV- aBSCC group (P < 0.0001). MTOR and PIK3CA pathway GA were not significantly different in the 2 groups. Putative biomarkers associated with immunotherapy (IO) response, including MSI and TMB status, were also similar in the 2 groups. PD-L1 expression data was available for a subset of both HPV+ and HPV- cases and showed high frequencies of positive staining which was not different in the 2 groups. CONCLUSIONS: HPV+ aBSCC tends to occur more often in younger patients. As reported in other HPV-associated squamous cell carcinomas, HPV+ aBSCC demonstrates significantly reduced frequencies of inactivating mutations in cell cycle regulatory genes with similar GA in MTOR and PIK3CA pathways. The implication of HPV in the pathogenesis of bladder cancer remains unknown but warrants further exploration and clinical validation.

[Clinicopathological features of rectal adenocarcinoma with enteroblastic differentiation].

Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.

Marginal proportional hazards models for multivariate interval-censored data.

Multivariate interval-censored data arise when there are multiple types of events or clusters of study subjects, such that the event times are potentially correlated and when each event is only known to occur over a particular time interval. We formulate the effects of potentially time-varying covariates on the multivariate event times through marginal proportional hazards models while leaving the dependence structures of the related event times unspecified. We construct the nonparametric pseudolikelihood under the working assumption that all event times are independent, and we provide a simple and stable EM-type algorithm. The resulting nonparametric maximum pseudolikelihood estimators for the regression parameters are shown to be consistent and asymptotically normal, with a limiting covariance matrix that can be consistently estimated by a sandwich estimator under arbitrary dependence structures for the related event times. We evaluate the performance of the proposed methods through extensive simulation studies and present an application to data from the Atherosclerosis Risk in Communities Study.

[Primary α-fetoprotein positive hepatoid adenocarcinoma of the lung: a case report].

This paper reports the data of a patient who was admitted to hospital for "cough with blood in sputum for 6 months" and diagnosed with α-fetoprotein(AFP) positive primary hepatoid adenocarcinoma of the lung. The patient was an 83-year-old male with a history of smoking for more than 60 years. Tumor indicators of patients were: AFP>3 000 ng/ml, carcinoembryonic antigen(CEA) 31.5 ng/ml, CA724 46.90 U/ml, Cyfra21-1 10.20 ng/ml, NSE 18.50 ng/ml, and the pathological findings of percutaneous lung biopsy showed that poorly differentiated cancer with significant necrosis. Combined with the results of immunohistochemistry and clinical laboratory examination, it is considered as metastatic hepatocellular carcinoma. PET-CT showed that FDG metabolism of multiple lymph nodes in the right lower lung, part of the pleura and mediastinum was increased, and the FDG metabolism in the liver or other systems/tissues was normal. Based on these results, it was diagnosed as AFP positive primary hepatoid adenocarcinoma of the lung, and the tumor stage was T4N3M1a(IVA). Through the data of the patient and the existing literature and reviews, we can get the tumor characteristics, diagnosis, treatment and prognosis of HAL, and improve the level of diagnosis and treatment of HAL by clinicians.

[Effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant in Guangdong Province].

Objective: To evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q1, Q3)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q1, Q3)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.

Tumor purity-associated genes influence hepatocellular carcinoma prognosis and tumor microenvironment.

Introduction: Tumor purity takes on critical significance to the progression of solid tumors. The aim of this study was at exploring potential prognostic genes correlated with tumor purity in hepatocellular carcinoma (HCC) by bioinformatics analysis. Methods: The ESTIMATE algorithm was applied for determining the tumor purity of HCC samples from The Cancer Genome Atlas (TCGA). The tumor purity-associated genes with differential expression (DEGs) were identified based on overlap analysis, weighted gene co-expression network analysis (WGCNA), and differential expression analysis. The prognostic genes were identified in terms of the prognostic model construction based on the Kaplan-Meier (K-M) survival analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses. The expression of the above-described genes was further validated by the GSE105130 dataset from the Gene Expression Omnibus (GEO) database. We also characterized the clinical and immunophenotypes of prognostic genes. Gene set enrichment analysis (GSEA) was carried out for exploring the biological signaling pathway. Results: A total of 26 tumor purity-associated DEGs were identified, which were involved in biological processes such as immune/inflammatory responses and fatty acid elongation. Ultimately, we identified ADCK3, HK3, and PPT1 as the prognostic genes for HCC. Moreover, HCC patients exhibiting higher ADCK3 expression and lower HK3 and PPT1 expressions had a better prognosis. Furthermore, high HK3 and PPT1 expressions and low ADCK3 expression resulted in high tumor purity, high immune score, high stromal score, and high ESTIMATE score. GSEA showed that the abovementioned prognostic genes showed a significant correlation with immune-inflammatory response, tumor growth, and fatty acid production/degradation. Discussion: In conclusion, this study identified novel predictive biomarkers (ADCK3, HK3, and PPT1) and studied the underlying molecular mechanisms of HCC pathology initially.

An Efficient Greedy Search Algorithm for High-dimensional Linear Discriminant Analysis.

High-dimensional classification is an important statistical problem that has applications in many areas. One widely used classifier is the Linear Discriminant Analysis (LDA). In recent years, many regularized LDA classifiers have been proposed to solve the problem of high-dimensional classification. However, these methods rely on inverting a large matrix or solving large-scale optimization problems to render classification rules-methods that are computationally prohibitive when the dimension is ultra-high. With the emergence of big data, it is increasingly important to develop more efficient algorithms to solve the high-dimensional LDA problem. In this paper, we propose an efficient greedy search algorithm that depends solely on closed-form formulae to learn a high-dimensional LDA rule. We establish theoretical guarantee of its statistical properties in terms of variable selection and error rate consistency; in addition, we provide an explicit interpretation of the extra information brought by an additional feature in a LDA problem under some mild distributional assumptions. We demonstrate that this new algorithm drastically improves computational speed compared with other high-dimensional LDA methods, while maintaining comparable or even better classification performance.

[Clinical management and prognosis for descending necrotizing mediastinitis].

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

Evaluation of the EQ-5D-5L, EQ-VAS stand-alone component and Oxford knee score in the Australian knee arthroplasty population utilising minimally important difference, concurrent validity, predictive validity and responsiveness.

PURPOSE: To evaluate the Oxford Knee Score (OKS), EQ-5D-5L utility index and EQ-5D visual analogue scale (EQ-VAS) for health-related quality of life outcome measurement in patients undergoing elective total knee arthroplasty (TKA) surgery. METHODS: In this prospective multi-centre study, the OKS and EQ-5D-5L index scores were collected preoperatively, six weeks (6w) and six months (6 m) following TKA. The OKS, EQ-VAS and EQ-5D-5L index were evaluated for minimally important difference (MID), concurrent validity, predictive validity (Spearman's Rho of predicted and observed values from a generalised linear regression model (GLM)), responsiveness (effect size (ES) and standard response mean (SRM)). The MID for the individual patient was determined utilising two approaches; distribution-based and anchor-based. RESULTS: 533 patients were analysed. The EQ-5D-5L utility index showed good concurrent validity with the OKS (r = 0.72 preoperatively, 0.65 at 6w and 0.69 at 6 m). Predictive validity for the EQ-5D-5L index was lower than OKS when regressed. Responsiveness was large for all fields at 6w for the EQ-5D-5L and OKS (EQ-5D-5L ES 0.87, SRM 0.84; OKS ES 1.35, SRM 1.05) and 6 m (EQ-5D-5L index ES 1.31, SRM 0.95; OKS ES 1.69, SRM 1.59). The EQ-VAS returned poorer results, at 6w an ES of 0.37 (small) and SRM of 0.36 (small). At 6 m, the EQ-VAS had an ES of 0.59 (moderate) and SRM of 0.47 (small). It, however, had similar predictive validity to the OKS, and better than the EQ-5D-5L index. MID determined using anchor approach, was shown that for OKS at 6 weeks it was 8.84 ± 9.28 and at 6 months 13.37 ± 9.89. For the EQ-5D-5L index at 6 weeks MID was 0.23 ± 0.39, and at 6 months 0.26 ± 0.36. CONCLUSIONS: The EQ-5D-5L index score and the OKS demonstrate good concurrent validity. The EQ-5D-5L index demonstrated lower predictive validity at 6w, and 6 m than the OKS, and both PROMs had adequate responsiveness. The EQ-VAS had poorer responsiveness but better predictive validity than the EQ-5D-5L index. This article includes MID estimates for the Australian knee arthroplasty population.

PENALIZED REGRESSION FOR MULTIPLE TYPES OF MANY FEATURES WITH MISSING DATA.

Recent technological advances have made it possible to measure multiple types of many features in biomedical studies. However, some data types or features may not be measured for all study subjects because of cost or other constraints. We use a latent variable model to characterize the relationships across and within data types and to infer missing values from observed data. We develop a penalized-likelihood approach for variable selection and parameter estimation and devise an efficient expectation-maximization algorithm to implement our approach. We establish the asymptotic properties of the proposed estimators when the number of features increases at a polynomial rate of the sample size. Finally, we demonstrate the usefulness of the proposed methods using extensive simulation studies and provide an application to a motivating multi-platform genomics study.