A Time-Varying Dynamic Partial Credit Model to Analyze Polytomous and Multivariate Time Series Data.

The accessibility to electronic devices and the novel statistical methodologies available have allowed researchers to comprehend psychological processes at the individual level. However, there are still great challenges to overcome as, in many cases, collected data are more complex than the available models are able to handle. For example, most methods assume that the variables in the time series are measured on an interval scale, which is not the case when Likert-scale items were used. Ignoring the scale of the variables can be problematic and bias the results. Additionally, most methods also assume that the time series are stationary, which is rarely the case. To tackle these disadvantages, we propose a model that combines the partial credit model (PCM) of the item response theory framework and the time-varying autoregressive model (TV-AR), which is a popular model used to study psychological dynamics. The proposed model is referred to as the time-varying dynamic partial credit model (TV-DPCM), which allows to appropriately analyze multivariate polytomous data and nonstationary time series. We test the performance and accuracy of the TV-DPCM in a simulation study. Lastly, by means of an example, we show how to fit the model to empirical data and interpret the results.

Evidence of bovine leukemia virus circulating in sheep and buffaloes in Colombia: insights into multispecies infection.

Bovine leukemia virus (BLV) is the causative agent of leukemia/lymphoma in cattle. However, previous evidence has shown its presence in other species of livestock as well as in humans, suggesting that other species can be accidental hosts of the virus. In viral infections, receptors that are common to different animal species are proposed to be involved in cross-species infections. For BLV, AP3D1 has been proposed to be its receptor, and this protein is conserved in most mammalian species. In Colombia, BLV has been reported in cattle with high prevalence rates, but there has been no evidence of BLV infections in other animal species. In this study, we tested for the virus in sheep (n = 44) and buffaloes (n = 61) from different regions of Colombia by nested PCR, using peripheral blood samples collected from the animals. BLV was found in 25.7% of the animals tested (12 buffaloes and 15 sheep), and the results were confirmed by Sanger sequencing. In addition, to gain more information about the capacity of the virus to infect these species, the predicted interactions of AP3D1 of sheep and buffaloes with the BLV-gp51 protein were analyzed in silico. Conserved amino acids in the binding domains of the proteins were identified. The detection of BLV in sheep and buffaloes suggests circulation of the virus in multiple species, which could be involved in dissemination of the virus in mixed livestock production settings. Due to the presence of the virus in multiple species and the high prevalence rates observed, integrated prevention and control strategies in the livestock industry should be considered to decrease the spread of BLV.

Structure and antimicrobial activity of phloroglucinol derivatives from Achyrocline satureioides.

The new prenylated phloroglucinol α-pyrones 1-3 and the new dibenzofuran 4, together with the known 23-methyl-6-O-demethylauricepyrone (5), achyrofuran (6), and 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphaliin A), were isolated from the aerial parts of Achyrocline satureioides. Their structures were determined by 1D and 2D NMR spectroscopic studies, while the absolute configuration of the sole stereogenic center of 1 was established by vibrational circular dichroism measurements in comparison to density functional theory calculated data. The same (S) absolute configuration of the α-methylbutyryl chain attached to the phloroglucinol nucleus was assumed for compounds 2-6 based on biogenetic considerations. Derivatives 7-16 were prepared from 1 and 5, and the antimicrobial activities of the isolated metabolites and some of the semisynthetic derivatives against a selected panel of Gram-positive and Gram-negative bacteria, as well as a set of yeast molds, were determined.

Diagnóstico y tratamiento de la pancreatitis aguda en la Argentina. Resultados de un estudio prospectivo en 23 centros.

In Argentina there are no multicenter studies evaluating the management of patients with acute pancreatitis (AP) nationwide. OBJECTIVES: The main objective of this study is to know how the patients with AP are treated in Argentina. The secondary objective is to assess whether the results comply with the recommendation of the American College of Gastroenterology Guide. MATERIAL AND METHODS: Twenty three center participated in the study. They include in a database hosted online consecutive patients with acute pancreatitis from june 2010 to june 2013. RESULTS: 854 patients entered the study. The average age was 46.6 years and 495 (58%) belonged to the female sex. The most common cause (88.2%) of AP was biliary. Some prognostic system was used in 99 % of patients and the most used was Ranson (74.5%). Were classified as mild 714 (83.6%) patients and severe 140 (16.4%). Systemic complications occurred in 43 patients and local complications in 21. 86 patients underwent dynamic CT scans and 73 patients had pancreatic and / or peripancreatic necrosis. Mortality was 1.5%. There was no difference in mortality in relation to the size, complexity or affiliation of the center. The comply of key recommendations of the American College of Gastroenterology Guide was over 80%. CONCLUSIONS: The diagnosis and treatment of patients with AP in 23 health centers located throughout the country was optimal. The management complied with most of the recommendations of the American College of Gastroenterology Guide.

Diagnóstico y tratamiento de la pancreatitis aguda en la Argentina. Resultados de un estudio prospectivo en 23 centros.

In Argentina there are no multicenter studies evaluating the management of patients with acute pancreatitis (AP) nationwide. OBJECTIVES: The main objective of this study is to know how the patients with AP are treated in Argentina. The secondary objective is to assess whether the results comply with the recommendation of the American College of Gastroenterology Guide. MATERIAL AND METHODS: Twenty three center participated in the study. They include in a database hosted online consecutive patients with acute pancreatitis from june 2010 to june 2013. RESULTS: 854 patients entered the study. The average age was 46.6 years and 495 (58%) belonged to the female sex. The most common cause (88.2%) of AP was biliary. Some prognostic system was used in 99 % of patients and the most used was Ranson (74.5%). Were classified as mild 714 (83.6%) patients and severe 140 (16.4%). Systemic complications occurred in 43 patients and local complications in 21. 86 patients underwent dynamic CT scans and 73 patients had pancreatic and / or peripancreatic necrosis. Mortality was 1.5%. There was no difference in mortality in relation to the size, complexity or affiliation of the center. The comply of key recommendations of the American College of Gastroenterology Guide was over 80%. CONCLUSIONS: The diagnosis and treatment of patients with AP in 23 health centers located throughout the country was optimal. The management complied with most of the recommendations of the American College of Gastroenterology Guide.

Bioinformatic survey for new physiological substrates of Cyclin-dependent kinase 5.

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase predominantly active in the nervous system where it regulates several processes such as neuronal migration, cytoskeletal dynamics, axonal guidance, and neurotransmission. We constructed a position specific scoring matrix (PSSM) based on a dataset of sites shown to be phosphorylated both in vivo and in vitro by Cdk5. This dataset was curated manually through an exhaustive search of published experimental data. We then used this PSSM to perform a search in the mouse proteome through Scansite, a web-based tool for matching sequence patterns in large databases. Considering a stringent cut-off score of 0.5, we identified 354 new putative sites present in 291 proteins. In order to assess the robustness of our results, ten random subsets (of 80 sites each) of the original dataset were used to construct new PSSMs, which were then used as input for a new Scansite search, leading to the recovery of 81% of the 354 sites by at least 5 PSSMs. In order to reduce the number of false positives in our sequence-based approach, we evaluated which of these predicted sites were phosphorylated in vivo as determined by multiple phosphoproteomics studies carried out through mass spectrometry and available in the PhosphoSitePlus database. This step resulted in a very promising list of 132 putative phosphorylation sites for Cdk5, of which, 51 are specifically phosphorylated in brain tissue, and some are involved in functions regulated by Cdk5 such as axonal growth, synaptic plasticity and neurotransmission. Other phosphorylation sites in our list suggest that Cdk5 might regulate processes through mechanisms not previously recognized such as the control of mRNA splicing.

Assessment of fit of the time-varying dynamic partial credit model using the posterior predictive model checking method.

Several new models based on item response theory have recently been suggested to analyse intensive longitudinal data. One of these new models is the time-varying dynamic partial credit model (TV-DPCM; Castro-Alvarez et al., Multivariate Behavioral Research, 2023, 1), which is a combination of the partial credit model and the time-varying autoregressive model. The model allows the study of the psychometric properties of the items and the modelling of nonlinear trends at the latent state level. However, there is a severe lack of tools to assess the fit of the TV-DPCM. In this paper, we propose and develop several test statistics and discrepancy measures based on the posterior predictive model checking (PPMC) method (PPMC; Rubin, The Annals of Statistics, 1984, 12, 1151) to assess the fit of the TV-DPCM. Simulated and empirical data are used to study the performance of and illustrate the effectiveness of the PPMC method.

Molecular epidemiology of plasmid-mediated high-level mupirocin resistance in methicillin-resistant Staphylococcus aureus in four Spanish health care settings.

Mupirocin is used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA). High-level mupirocin resistance (Hi-Mup(R)) is of concern, having been associated with therapeutic failure. Our main objective was to assess the emergence and mode/s of spread of Hi-Mup(R) in the MRSA population recovered between 2002 and 2009 in four health care settings in the Pontevedra province, northwest Spain. Five hundred and fifty consecutive clinical MRSA isolates were obtained and screened for antimicrobial susceptibility. Isolates were stratified into multidrug-resistant (MDR) and non-MDR. High-level mupirocin resistant MRSA were characterized by genotyping and plasmid analysis. Thirty-one MRSA (5.6%) exhibited Hi-Mup(R). No association was detected between Hi-Mup(R) and MDR but isolates displaying Hi-Mup(R) were more likely to be resistant to gentamicin and tobramycin. Four main MRSA clones were identified: ST125/t067/PFGE A, ST36/t018/PFGE D, ST8/t008/PFGE B, and ST72/t148 or t3092/PFGE B. Each isolate carried the Hi-Mup(R)ileS2-encoding gene on plasmids and ten plasmid types were distinguished based on unique IS257-ileS2 configurations. Some plasmid types were successfully disseminated among the MRSA clones. Remarkably, six plasmid types were acquired by the predominant genotype ST125/t067/PFGE A. In conclusion, molecular characterization of MRSA isolates combined with the rapid typing of ileS2-encoding plasmids through determination of IS257-ileS2 configurations have proved to be a powerful strategy to address the molecular epidemiology of Hi-Mup(R). The transmission of a diverse set of ileS2-carrying plasmids promoted the emergence of the resistance, with a limited role of clonal expansion in its dispersion.

Multicomponent synthesis of antibacterial dihydropyridin and dihydropyran embelin derivatives.

A series of dihydropyran and dihydropyridin embelin derivatives were synthesized through a novel and straightforward one-pot protocol based on a three-component reaction with embelin, aldehydes, and cyclic enaminones as synthetic imputs. The type of substituent on the nitrogen atom of the ß-enaminone is key to obtain nitrogenated or oxygenated rings. The obtained compounds were active against Gram-positive bacteria, including multiresistant Staphylococcus aureus clinical isolates.

Racial and ethnic variation in referral times for thoracic oncologic surgery in a major metropolitan area.

OBJECTIVE: The study objective was to understand the impact of race/ethnicity on access to thoracic surgical care for patients undergoing lung resection for cancer. METHODS: We performed a retrospective analysis on 206 consecutive patients who underwent lung resection for cancer (120 female, 86 male; median age 66 years), with respect to how race and ethnicity impact time to referral for thoracic surgery to a major healthcare center. Time between initial radiographic appearance of a lung nodule/mass 1 cm or greater to surgical referral and time from surgical referral to operation were evaluated for 121 White, 30 Asian, 26 Hispanic, 12 African American, and 17 mixed or other race patients. The impact of age, sex, median income of patient's household, national and state Area Deprivation Indices, insurance type, and distance between the patient's domicile and our hospital was evaluated. The influence of the referring physician's practice (hospital-based, hospital-affiliated, or private), internal or external referral, race/ethnicity, and level of specialization was also studied. RESULTS: African American, Asian, Hispanic, and mixed/other race patients had significantly longer wait times between initial radiographic finding of a lung nodule/mass 1 cm or greater and surgical referral compared with White individuals (median days: African American, 78; Asian, 95; Hispanic, 92; mixed or other, 65; White, 35). Multiple linear regression analysis demonstrated that race/ethnicity was the only significant predictor of prolonged time to surgical referral when adjusted for age, sex, median household income level, national and state Area Deprivation Indices, insurance type, and distance between patient's home and our hospital. The referring physician's type of practice and internal versus external referral were not significant. However, the physician's race/ethnicity and level of specialization had an impact on referral times, with nonspecialists referring patients sooner to thoracic surgery compared with specialists who ordered more workup tests. For all patient races/ethnicities, there was no difference in time between surgical referral and day of operation. CONCLUSIONS: Race and ethnicity have a major impact on the time from initial radiographic appearance of a lung nodule/mass 1 cm or greater to referral for surgical resection for cancer. This study suggests the need to develop strategies to reduce minority wait times and improve timely access to surgery for patients with thoracic malignancies. VIDEO ABSTRACT: Discussion of how race and ethnicity impact referral time to thoracic surgery discussed by Dr Moises Hernandez.

The Comorbidities, Radiographic Findings, Age, and Lymphopenia (CORAL) Tool: A Diagnostic Ally for Emergency Physicians Created for the COVID-19 Crisis and Beyond.

BACKGROUND: This study aimed to develop a novel clinical approach to predict intensive care unit (ICU) admission and mortality among coronavirus disease 2019 (COVID-19) patients in the emergency department (ED). METHODS: A retrospective cohort study was conducted including adults ≥ 18 years diagnosed with COVID-19 in the emergency department and admitted to the ICU between March and July 2020 in an academic hospital. The outcome variables were mortality and ICU admission. Additional variables that were collected included sex, age, comorbidities, symptom phenotype, and laboratory (lymphopenia) and imaging findings. A logistic regression model was used to construct and validate the risk models. RESULTS: A total of 808 patients were included in the study; 61.9% were men. The mean age was 57.8 ± 15.9 years, and high blood pressure (HBP) was the most prevalent comorbidity (31.8%). Seventy-six (9.4%) patients were admitted to the ICU. Age ≥ 60 years, chronic obstructive pulmonary disease (COPD), lymphopenia, and imaging findings correlated with mortality. Age ≥ 60 years, lymphopenia (<1,000 cells per microliter), and hypothyroidism correlated with ICU admission. These variables were incorporated into a scoring system (Comorbidities, Radiographic findings, Age, and Lymphopenia (CORAL) tool) to predict mortality and ICU admission. CONCLUSIONS: Our Comorbidities, Radiographic findings, Age, and Lymphopenia (CORAL) tool is a practical tool for different clinical settings independent of access to advanced medical resources or technologies. CORAL is suitable for emergency physicians in low- and middle-income countries.

Transorbital penetrating intracranial injury, with cavernous sinus involvement.

Transorbitary intracranial penetrating traumatic injuries are uncommon in the paediatric population, and may occur in the context of domestic, sporting or school accidents. They can extend to skull base and compromise vascular structures such as cavernous sinus and internal carotid. We present a case of 6 years-old girl that suffered an intracranial transorbital penetrating injury with a wooden pencil that crossed from the medial edge of left orbit, transetmoidal and trans-sphenoidal, entering the right sellar region and leaving its end in contact with carotid artery (cavernous segment). After pre-surgical studies, foreign body removal was performed with endoscopic surgery + endovascular control in case of carotid injury. After removing the foreign body, a CSF fistula occurred and was repaired. Patient recovered adequately, without neurological deficit, without postoperative CSF fistula, without CNS infection or oculomotor alteration.

JAGGED-NOTCH3 signaling in vascular remodeling in pulmonary arterial hypertension.

Within the pulmonary arterial tree, the NOTCH3 pathway is crucial in controlling vascular smooth muscle cell proliferation and maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (PAH) is a fatal disease without cure, characterized by elevated pulmonary vascular resistance due to vascular smooth muscle cell proliferation in precapillary arteries, perivascular inflammation, and asymmetric neointimal hyperplasia. Here, we show that human PAH is characterized by overexpression of the NOTCH ligand JAGGED-1 (JAG-1) in small pulmonary artery smooth muscle cells and that JAG-1 selectively controls NOTCH3 signaling and cellular proliferation in an autocrine fashion. In contrast, the NOTCH ligand DELTA-LIKE 4 is minimally expressed in small pulmonary artery smooth muscle cells from individuals with PAH, inhibits NOTCH3 cleavage and signaling, and retards vascular smooth muscle cell proliferation. A new monoclonal antibody for the treatment of PAH, which blocks JAG-1 cis- and trans-induced cleavage of the NOTCH3 receptor in the pulmonary vasculature, was developed. Inhibition of JAG-1-induced NOTCH3 signaling in the lung reverses clinical and pathologic pulmonary hypertension in two rodent models of disease, without toxic side effects associated with nonspecific NOTCH inhibitors. Our data suggest opposing roles of NOTCH ligands in the pulmonary vasculature in pulmonary hypertension. We propose that selectively targeting JAG-1 activation of NOTCH3 may be an effective, safe strategy to treat PAH.

Using structural equation modeling to study traits and states in intensive longitudinal data.

Traditionally, researchers have used time series and multilevel models to analyze intensive longitudinal data. However, these models do not directly address traits and states which conceptualize the stability and variability implicit in longitudinal research, and they do not explicitly take into account measurement error. An alternative to overcome these drawbacks is to consider structural equation models (state-trait SEMs) for longitudinal data that represent traits and states as latent variables. Most of these models are encompassed in the latent state-trait (LST) theory. These state-trait SEMs can be problematic when the number of measurement occasions increases. As they require the data to be in wide format, these models quickly become overparameterized and lead to nonconvergence issues. For these reasons, multilevel versions of state-trait SEMs have been proposed, which require the data in long format. To study how suitable state-trait SEMs are for intensive longitudinal data, we carried out a simulation study. We compared the traditional single level to the multilevel version of three state-trait SEMs. The selected models were the multistate-singletrait (MSST) model, the common and unique trait-state (CUTS) model, and the trait-state-occasion (TSO) model. Furthermore, we also included an empirical application. Our results indicated that the TSO model performed best in both the simulated and the empirical data. To conclude, we highlight the usefulness of state-trait SEMs to study the psychometric properties of the questionnaires used in intensive longitudinal data. Yet, these models still have multiple limitations, some of which might be overcome by extending them to more general frameworks. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does Functional Somatic Symptoms Measurement Differ Across Sex and Age? Differential Item Functioning in Somatic Symptoms Measured With the CIDI.

Functional Somatic Symptoms (FSS) are physical symptoms that cannot be attributed to underlying pathology. Their severity is often measured with sum scores on questionnaires; however, this may not adequately reflect FSS severity in subgroups of patients. We aimed to identify the items of the somatization section of the Composite International Diagnostic Interview that best discriminate FSS severity levels, and to assess their functioning in sex and age subgroups. We applied the two-parameter logistic model to 19 items in a population-representative cohort of 962 participants. Subsequently, we examined differential item functioning (DIF). "Localized (muscle) weakness" was the most discriminative item of FSS severity. "Abdominal pain" consistently showed DIF by sex, with males reporting it at higher FSS severity. There was no consistent DIF by age, however, "Joint pain" showed poor discrimination of FSS severity in older adults. These findings could be helpful for the development of better assessment instruments for FSS, which can improve both future research and clinical care.

PCR-based amplification of heterogeneous IS257-ileS2 junctions for molecular monitoring of high-level mupirocin resistance in staphylococci.

OBJECTIVES: Plasmids encoding the ileS2 gene are responsible for the wide spread of high-level mupirocin resistance in staphylococci, and consequent clinical and epidemiological problems. We investigated the location of insertion sequence IS257 flanking ileS2 in different plasmids and developed a method for molecular typing of the IS257-ileS2 spacer regions. METHODS: Nine ileS2-encoding plasmids (i.e. pPR1-pPR9) classified into distinct structural groups (i.e. S1-S4) were analysed. Complete DNA sequences between IS257s flanking ileS2 were determined. A PCR-based amplification scheme was designed for the simultaneous amplification of up- and down-stream IS257-ileS2 regions. The method was applied to a total of 90 high-level mupirocin-resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: pPR1-pPR9 possessed IS257s flanking ileS2. Plasmids of each structural group showed a unique configuration of IS257-ileS2 spacer regions. The PCR-based method permitted accurate typing of the heterogeneous IS257-ileS2 up- and down-stream junctions, and the differentiation of plasmids of each group. The results obtained corresponded with previous plasmid typing based on restriction enzyme analyses and ileS2 locus hybridization polymorphs. The application of the PCR-based method to a diverse collection of MRSA isolates carrying ileS2-encoding plasmids demonstrated its versatility and revealed extraordinary heterogeneity in the IS257-ileS2 spacers. CONCLUSIONS: The devised PCR-based scheme offers a rapid, simple and effective approach for typing IS257-ileS2 configurations present on ileS2-encoding plasmids. Hopefully, it could serve as a useful molecular epidemiological tool to control high-level mupirocin resistance.

New Staphylococcus aureus genetic cluster associated with infectious osteomyelitis.

Diverse genotyping methods, including multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA), pulsed field gel electrophoresis (PFGE), and multilocus sequence typing (MLST), were used for genotyping Staphylococcus aureus in samples recovered from a clinical case of osteomyelitis. An unexpected genetic diversity of strains was determined, including four new sequence types (ST 1521, 1522, 1628 and 1629) belonging to the same genetic lineage, implying the appearance of a new subgroup derived from clonal complex CC121 isolated from that hospital. A close phylogenetic relationship among the STs was demonstrated, reflecting a possible diversifying evolution process. To our knowledge, there have no been previous reports of staphylococcal genetic variability observed within a single individual with such a high degree of variation. These findings emphasize the need for infection control measures to monitor the high genetic variability continuously occurring in this often dangerous infectious agent.

Co-Circulation of Bovine Leukemia Virus Haplotypes among Humans, Animals, and Food Products: New Insights of Its Zoonotic Potential.

Bovine leukemia virus (BLV) is the causative agent of leukemia/lymphoma in cattle. It has been found in humans and cattle-derived food products. In humans, it is described as a potential risk factor for breast cancer development. However, the transmission path remains unclear. Here, a molecular epidemiology analysis was performed to identify signatures of genetic flux of BLV among humans, animals, and food products. Sequences obtained from these sources in Colombia were used (n = 183) and compared with reference sequences available in GenBank. Phylogenetic reconstruction was performed in IQ-TREE software with the maximum likelihood algorithm. Haplotype (hap) distribution among the population was carried out with a median-joining model in Network5.0. Recombination events were inferred using SplitsTree4 software. In the phylogenetic analysis, no specific branches were identified for the Colombian sequences or for the different sources. A total of 31 haps were found, with Hap 1, 4, 5 and 7 being shared among the three sources of the study. Reticulation events among the different sources were also detected during the recombination analysis. These results show new insights about the zoonotic potential of BLV, showing evidence of genetic flux between cattle and humans. Prevention and control strategies should be considered to avoid viral dissemination as part of the One Health program policies.

Complete nucleotide sequence and comparative analysis of pPR9, a 41.7-kilobase conjugative staphylococcal multiresistance plasmid conferring high-level mupirocin resistance.

We have sequenced the conjugative plasmid pPR9, which carries the ileS2 gene, which had contributed to the dissemination of high-level mupirocin resistance at our institution. The plasmid backbone shows extensive genetic conservation with plasmids belonging to the pSK41/pGO1 family, but comparative analyses have revealed key differences that provide important insights into the evolution of these medically important plasmids and high-level mupirocin resistance in staphylococci and highlight the role of insertion sequence IS257 in these processes.

Evaluation of multiple-locus variable-number tandem-repeat analysis for typing a polyclonal hospital-acquired methicillin-resistant Staphylococcus aureus population in an area where such infections are endemic.

Multiple-locus variable-number tandem-repeat analysis (MLVA) was performed with 292 methicillin-resistant Staphylococcus aureus (MRSA) isolates previously characterized by pulsed-field gel electrophoresis, multilocus sequence typing, and staphylococcal cassette chromosome mec typing. Quantitative correspondence analyses showed the best correlation between data when an >or=80% cutoff was applied to MLVA. We confirmed the validity of MLVA for identification of related strains in a polyclonal MRSA population.