Ordinal Probit Functional Regression Models with Application to Computer-Use Behavior in Rhesus Monkeys

Research in functional regression has made great strides in expanding to non-Gaussian functional outcomes, however the exploration of ordinal functional outcomes remains limited. Motivated by a study of computer-use behavior in rhesus macaques (\emph{Macaca mulatta}), we introduce the Ordinal Probit Functional Regression Model or OPFRM to perform ordinal function-on-scalar regression. The OPFRM is flexibly formulated to allow for the choice of different basis functions including penalized B-splines, wavelets, and O'Sullivan splines. We demonstrate the operating characteristics of the model in simulation using a variety of underlying covariance patterns showing the model performs reasonably well in estimation under multiple basis functions. We also present and compare two approaches for conducting posterior inference showing that joint credible intervals tend to out perform point-wise credible. Finally, in application, we determine demographic factors associated with the monkeys' computer use over the course of a year and provide a brief analysis of the findings

Bayesian Function-on-Function Regression for Multilevel Functional Data

Medical and public health research increasingly involves the collection of complex and high dimensional data. In particular, functional data—where the unit of observation is a curve or set of curves that are finely sampled over a grid—is frequently obtained. Moreover, researchers often sample multiple curves per person resulting in repeated functional measures. A common question is how to analyze the relationship between two functional variables. We propose a general function-on-function regression model for repeatedly sampled functional data on a fine grid, presenting a simple model as well as a more extensive mixed model framework, and introducing various functional Bayesian inferential procedures that account for multiple testing. We examine these models via simulation and a data analysis with data from a study that used event-related potentials to examine how the brain processes various types of images

Characteristics of Clinical Shoulder Research Over the Last Decade: A Review of Shoulder Articles in \u3cem\u3eThe Journal of Bone & Joint Surgery\u3c/em\u3e from 2004 to 2014

Background: The purpose of this study was to determine characteristics and trends in published shoulder research over the last decade in a leading orthopaedic journal. Methods: We examined all clinical shoulder articles published in The Journal of Bone & Joint Surgery from 2004 to 2014. The number of citations, authorship, academic degrees of the authors, country and institution of origin, topic, level of evidence, positive or nonpositive outcome, and inclusion of validated patient-reported outcome measures were assessed for each article. Results: Shoulder articles that included an author with an advanced research degree (MD [Doctor of Medicine] with a PhD [Doctor of Philosophy] or other advanced degree) increased during the study period (p = 0.047). Level-I, II, and III studies were more likely to have an author with an advanced research degree, and Level-IV studies were more likely to have MDs only (p = 0.03). Overall, there was great variability of outcome measures, with at least thirty-nine different validated or nonvalidated outcome measures reported. Conclusions: Over the last decade, there was an improvement in the level of evidence of shoulder articles published in The Journal of Bone & Joint Surgery that corresponds with recent emphasis on evidence-based medicine. A consensus is needed in shoulder research for more consistent application of validated patient-reported outcome measurement tools

Moderating Effects of Immunosuppressive Medications and Risk Factors for Post-Operative Joint Infection Following Total Joint Arthroplasty in Patients with Rheumatoid Arthritis or Osteoarthritis

Objective—Inconclusive findings about infection risks, importantly the use of immunosuppressive medications, in patients who have undergone large-joint total joint arthroplasty challenge efforts to provide evidenced-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a postoperative infection in patients undergoing TJA of a large joint [total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty] by identifying clinical and demographic factors, including the use of high risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses (i.e., rheumatoid arthritis [RA], osteoarthritis [OA], gout, obesity, diabetes mellitus), that are linked to infection status, controlling for length of follow-up. Methods—A retrospective, case-control study (N = 2,212) using de-identified patient health claims information from a commercially-insured, U.S. dataset representing 15 million patients annually (January 1, 2007 - December 31, 2009) was conducted. Descriptive statistics, t-test, chi-square test, Fisher\u27s exact test, and multivariate logistic regression were used. Results—Male gender (OR = 1.42; p \u3c .001), diagnosis of RA (OR = 1.47; p = .031), diabetes mellitus (OR = 1.38, p = .001), obesity (OR = 1.66, p \u3c .001) or gout (OR = 1.95; p = .001), and a prescription for prednisone (OR = 1.59; p \u3c .001) predicted a post-operative infection following total joint arthroplasty. Persons with post-operative joint infections were significantly more likely to be prescribed allopurinol (p = .002) and colchicine (p = .006; no significant difference was found for the use of specific disease modifying anti-rheumatic drugs and TNF-α inhibitors. Conclusion—High-risk, post-operative joint infection groups were identified allowing for precautionary clinical measures to be taken

Dependence on a variable residue limits the breadth of an HIV MPER neutralizing antibody, despite convergent evolution with broadly neutralizing antibodies

Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10, VRC42.01 and PGZL1, can neutralize \u3e 80 % of viruses. These three MPER-directed monoclonal antibodies share germline antibody genes (IGHV1 - 69 and IGKV3 - 20) and form a bNAb epitope class. Furthermore, convergent evolution within these two lineages towards a 111.2GW111.3 motif in the CDRH3 is known to enhance neutralization potency. We have previously isolated an MPER neutralizing antibody, CAP206 - CH12, that uses these same germline heavy and light chain genes but lacks breadth (neutralizing only 6 % of heterologous viruses). Longitudinal sequencing of the CAP206-CH12 lineage over three years revealed similar convergent evolution towards 111.2GW111.3 among some lineage members. Mutagenesis of CAP206-CH12 from 111.2GL111.3 to 111.2GW111.3 and the introduction of the double GWGW motif into CAP206-CH12 modestly improved neutralization potency (2.5 3 -fold) but did not reach the levels of potency of VRC42.01, 4E10 or PGZL1. To explore the lack of potency/breadth, viral mutagenesis was performed to map the CAP206-CH12 epitope. This indicated that CAP206-CH12 is dependent on D674, a highly variable residue at the solvent-exposed elbow of MPER. In contrast, VRC42.01, PGZL1 and 4E10 were dependent on highly conserved residues (W672, F673, T676, andW680) facing the hydrophobic patch of the MPER. Therefore, while CAP206-CH12, VRC42.01, PGZL1 and 4E10 share germline genes and show some evidence of convergent evolution, their dependence on different amino acids, which impacts orientation of binding to the MPER, result in differences in breadth and potency. These data have implications for the design of HIV vaccines directed at the MPER epitope

Large differences in adiponectin levels have no clear effect on multiple sclerosis risk: A Mendelian randomization study.

BACKGROUND: Mendelian randomization (MR) studies have demonstrated strong support for an association between genetically increased body mass index and risk of multiple sclerosis (MS). The adipokine adiponectin may be a potential mechanism linking body mass to risk of MS. OBJECTIVE: To evaluate whether genetically increased adiponectin levels influence risk of MS. METHODS: Using genome-wide significant single nucleotide polymorphisms (SNPs) for adiponectin, we undertook an MR study to estimate the effect of adiponectin on MS. This method prevents bias due to reverse causation and minimizes bias due to confounding. Sensitivity analyses were performed to evaluate the assumptions of MR. RESULTS: MR analyses did not support a role for genetically elevated adiponectin in risk of MS (odds ratio (OR) = 0.93 per unit increase in natural-log-transformed adiponectin, equivalent to a two-standard deviation increase in adiponectin on the absolute scale; 95% confidence interval (CI) = 0.66-1.33; p = 0.61). Further MR analysis suggested that genetic variation at the adiponectin gene, which influences adiponectin level, does not impact MS risk. Sensitivity analyses, including MR-Egger regression, suggested no bias due to pleiotropy. CONCLUSION: Lifelong genetically increased adiponectin levels in humans have no clear effect on risk of MS. Other biological factors driving the association between body mass and MS should be investigated

Comparative Analysis of the Frequency and Distribution of Stem and Progenitor Cells in the Adult Mouse Brain

cells (NSCs) and progenitor cells, but it cannot discriminate between these two populations. Given two assays have purported to overcome this shortfall, we performed a comparative analysis of the distribution and frequency of NSCs and progenitor cells detected in 400 m coronal segments along the ventricular neuraxis of the adult mouse brain using the neurosphere assay, the neural colony forming cell assay (N-CFCA), and label-retaining cell (LRC) approach. We observed a large variation in the number of progenitor/stem cells detected in serial sections along the neuraxis, with the number of neurosphereforming cells detected in individual 400 m sections varying from a minimum of eight to a maximum of 891 depending upon the rostral-caudal coordinate assayed. Moreover, the greatest variability occurred in the rostral portion of the lateral ventricles, thereby explaining the large variation in neurosphere frequency previously reported. Whereas the overall number of neurospheres (3730 276) or colonies (4275 124) we detected along the neuraxis did not differ significantly, LRC numbers were significantly reduced (1186 188, 7 month chase) in comparison to both total colonies and neurospheres. Moreover, approximately two orders of magnitude fewer NSC-derived colonies (50 10) were detected using the N-CFCA as compared to LRCs. Given only 5% of the LRCs are cycling (BrdU/Ki-67) or competent to divide (BrdU/Mcm-2), and proliferate upon transfer to culture, it is unclear whether this technique selectively detects endogenous NSCs. Overall, caution should be taken with the interpretation and employment of all these techniques

Results of the combined U.S. multicenter postapproval study of the Nit‐Occlud PDA device for percutaneous closure of patent ductus arteriosus

ObjectivesTo report the results of the Nit‐Occlud PDA prospective postapproval study (PAS) along with a comparison to the results of the pivotal and continued access trials.BackgroundThe Nit‐Occlud PDA (PFM Medical, Cologne, Germany), a nitinol coil patent ductus arteriosus (PDA) occluder, was approved by the Food and Drug Administration in 2013.MethodsThe PAS enrolled a total of 184 subjects greater than 6 months of age, weighing at least 5 kg, with PDAs less than 4 mm by angiography at 11 centers. Patients were followed prospectively at 2 months, 12 months, and 24 months postprocedure. These outcomes were compared to the 357 subjects enrolled in the pivotal and continued access protocols. Efficacy and safety data were reported.ResultsAmong 184 subjects enrolled for the PAS between 2014 and 2017, 180 (97.8%) had successful device implantation. After 12 months, 98.7% (150/152) had trivial or no residual shunt by echocardiography and two subjects had only small residual shunts. There were three device embolizations that were all retrieved by snare without clinical consequence. Together with the pivotal and continued access study, 97.4% (449/461) had complete echocardiographic closure at 12 months in 541 enrolled subjects. The composite success was 94.4%. There were no mortalities and no serious device‐related adverse events.ConclusionsThe Nit‐Occlud PDA is a safe and effective device for closure of a small to moderate sized PDA. There were no serious device‐related adverse events in a large cohort of three clinical trials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148398/1/ccd27995_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148398/2/ccd27995.pd