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BackgroundIn dogs undergoing vertebral column stabilization, post-operative computed tomography (CT) evaluates implant placement. The impact on the interpretation of metallic artifact associated with titanium implants in dogs remains to be established. Our objective was to quantify metallic artifact on CT associated with titanium pedicle screws.MethodsThe study design included an in vitro model and a retrospective review of 11 dogs with vertebral column stabilization. Twenty four titanium pedicle screws (6 each: 2.0 mm, 2.7 mm, 3.5 mm, and 4.5 mm) were inserted into a 20% ballistic gel, and CT scan of the construct was performed. Three blinded raters used a bone window to measure the maximum width (effective size) of each screw, one rater measured effective size using an ultrawide window and 45 titanium pedicle screws (3×2.0 mm, 5×2.7 mm, 30×3.5 mm, and 7×4.5 mm) in 11 clinical cases. Effective size measurements were compared to actual screw sizes.ResultsThe effective size was 26.9–43.8%, 9.2–18.5%, and 21.1–30.5% larger than the actual size for the in vitro system (bone window), in vitro system (ultrawide window), and clinical cases, respectively. The mean gross difference for the in vitro measurements varied by implant size (p

Abstract Immunotherapy has dramatically transformed the cancer treatment landscape largely due to the efficacy of immune checkpoint inhibitors (ICIs). Although ICIs have shown promising results for many patients, the low response rates in many cancers highlight the ongoing challenges in cancer treatment. Cytotoxic T lymphocytes (CTLs) execute their cell-killing function via two distinct mechanisms: a fast-acting, perforin-mediated process and a slower, Fas ligand (FasL)-driven pathway. Evidence also suggests that the preferred killing mechanism of CTLs depends on the antigenicity of tumor cells. To determine the critical factors affecting responses to ICIs, we construct an ordinary differential equation model describing in vivo tumor-immune dynamics in the presence of active or blocked PD-1/PD-L1 immune checkpoint. Specifically, we identify important aspects of the tumor-immune landscape that affect tumor size and composition in the short and long term. We also generate a virtual cohort of mice with diverse tumor and immune attributes to simulate the outcomes of immune checkpoint blockade in a heterogeneous population. By identifying key tumor and immune characteristics associated with tumor elimination, dormancy, and escape, we predict which fraction of a population potentially responds well to ICIs and ways to enhance therapeutic outcomes with combination therapy.

Bladder cancer is an increasingly prevalent global disease that continues to cause morbidity and mortality despite recent advances in treatment. Immune checkpoint inhibitors (ICI) and fibroblast growth factor receptor (FGFR)-targeted therapeutics have had modest success in bladder cancer when used as monotherapy. Emerging data suggests that the combination of these two therapies could lead to improved clinical outcomes, but the optimal strategy for combining these agents remains uncertain. Mathematical models, specifically agent-based models (ABMs), have shown recent successes in uncovering the multiscale dynamics that shape the trajectory of cancer. They have enabled the optimization of treatment methods and the identification of novel therapeutic strategies. To assess the combined effects of anti-PD-1 and anti-FGFR3 small molecule inhibitors (SMI) on tumor growth and the immune response, we built an ABM that captures key facets of tumor heterogeneity and CD8+ T cell phenotypes, their spatial interactions, and their response to therapeutic pressures. Our model quantifies how tumor antigenicity and FGFR3 activating mutations impact disease trajectory and response to anti-PD-1 antibodies and anti-FGFR3 SMI. We find that even a small population of weakly antigenic tumor cells bearing an FGFR3 mutation can render the tumor resistant to combination therapy. However, highly antigenic tumors can overcome therapeutic resistance mediated by FGFR3 mutation. The optimal therapy depends on the strength of the FGFR3 signaling pathway. Under certain conditions, ICI alone is optimal; in others, ICI followed by anti-FGFR3 therapy is best. These results indicate the need to quantify FGFR3 signaling and the fitness advantage conferred on bladder cancer cells harboring this mutation. This ABM approach may enable rationally designed treatment plans to improve clinical outcomes.

Abstract Positioned within the eye, the lens supports vision by transmitting and focusing light onto the retina. As an adaptive glassy material, the lens is constituted primarily by densely‐packed, polydisperse crystallin proteins that organize to resist aggregation and crystallization at high volume fractions, yet the details of how crystallins coordinate with one another to template and maintain this transparent microstructure remain unclear. The role of individual crystallin subtypes (α, β, and γ) and paired subtype compositions, including how they experience and resist crowding‐induced turbidity in solution, is explored using combinations of spectrophotometry, hard‐sphere simulations, and surface pressure measurements. After assaying crystallin combinations, β‐crystallins emerged as a principal component in all mixtures that enabled dense fluid‐like packing and short‐range order necessary for transparency. These findings helped inform the design of lens‐like hydrogel systems, which are used to monitor and manipulate the loss of transparency under different crowding conditions. When taken together, the findings illustrate the design and characterization of adaptive materials made from lens proteins that can be used to better understand mechanisms regulating transparency.

Abstract In this paper, we present the first high‐speed video observation of a cloud‐to‐ground lightning flash and its associated downward‐directed Terrestrial Gamma‐ray Flash (TGF). The optical emission of the event was observed by a high‐speed video camera running at 40,000 frames per second in conjunction with the Telescope Array Surface Detector, Lightning Mapping Array, interferometer, electric‐field fast antenna, and the National Lightning Detection Network. The cloud‐to‐ground flash associated with the observed TGF was formed by a fast downward leader followed by a very intense return stroke peak current of −154 kA. The TGF occurred while the downward leader was below cloud base, and even when it was halfway in its propagation to ground. The suite of gamma‐ray and lightning instruments, timing resolution, and source proximity offer us detailed information and therefore a unique look at the TGF phenomena.

Background: Instability is a common complication after revision total hip arthroplasty. Tripolar constrained (TC) and dual mobility (DM) liners cemented into tantalum acetabular revision (TM) shells are established alternatives that reduce instability risk. This study compares outcomes of TC and DM liners cemented into TM shells in complex revision hip replacements. Methods: Fifty cases using a TM shell and a TC or DM cemented liner with at least 12 months of follow-up were identified. There were 25 TC and 25 DM liners. Clinical, radiographic, and patient-reported outcomes were collected. Reasons for re-revision and failures were analyzed. Results: The average age was 73 years in the TC group and 75 years in the DM group. The median follow-up duration was 50 months (23 - 96) and 13 months (12 – 21) for the TC and DM groups, respectively. The mean Harris Hip Score improved from 37 to 61 for the TC group and from 51 to 73 in the DM group at the last review. Two TC cases required revision for wear and liner failure. One DM insert was changed at reoperation for periprosthetic femur fracture. There were no failures of cement fixation in either group and no revisions for cup loosening. Conclusions: In complex revision hip replacement with a history of instability or judged to have a high risk of instability postoperatively, TC and DM liners cemented into tantalum revision shells are both successful, giving acceptable results. The improved arc of movement with DM liners, minimizing impingement, makes them preferable except when there is a global abductor deficiency or severe joint laxity.

Background: The swelling of the lymph nodes may raise some concerns and anxiety for people after getting the vaccination, especially for COVID-19. Many women seek medical attention for the enlarged lymph node due to the known relationship between lymph nodes and breast cancer. This research is intended to enrich the data of the most recent COVID-19 pandemic and the vaccines that were developed shortly after. The aim is to see if there is an effect of early movement of the swollen axillary lymph nodes caused by the COVID-19 vaccination and to enrich the data of the most recent COVID-19 pandemic and its developed vaccines shortly after. Methods: A voluntary survey was used to collect data from recently vaccinated individuals. Data were analyzed for associations between early movement and resolution of lymphadenopathy. Results: 32 (20.38%) of 157 participants reported swelling of axillary lymph nodes that resulted from COVID-19 vaccination. Duration of swelling ranged from 1 to more than two weeks. The early movement did not show a statistically significant reduction in the course of swelling. Conclusion: Early movement of areas affected with lymph node enlargement, whether active or passive, does not seem to cause additional side effects. The effect of early action seems comparable to rest (see Fig.), although it may lessen erythema due to improved circulation, just like the newer concept of early movement after a skeletal injury has a better outcome than merely resting, which was the older method of recovery. However, the current data is limited to support the benefit of such a concept.

Bergman, Karikomi et al. propose a multiscale evolutionary model to describe tumor-immune-EMT interactions and their impact on epithelial cancer progression, which highlights a controllable region that maximizes invasion-free survival. Using EMT-inflammation associated TCGA data, the authors find EMT association worsens invasion-free survival and identify genes that influence outcomes in bladder and uterine cancer.

The award is given to Wolfgang Wiedermann, University of Missouri, Columbia, for his many contributions to new valuable methods for analyzing data in a person-oriented context. Wiedermann has often, but not exclusively, carried out his research within the framework of the configural frequency analysis (CFA) tradition, in many cases in collaboration with Alexander von Eye. The CFA framework is eminently well suited to provide a methodological toolbox for the researcher carrying out person-oriented analyses. Wiedermann has been a driving force in developing many new methods that not only extend the CFA approach but which also in a clever and creative way makes use of other types of statistical methods to find new types of solutions to methodological challenges.

OBJECTIVES:. As the use of extracorporeal membrane oxygenation (ECMO) expands, so has the need for interfacility transfer to ECMO centers. However, the impact of these transfers has not been fully studied. This study evaluates complications and inhospital mortality in adult patients treated with venovenous (V-V) ECMO based on institutional location of cannulation and mode of transport. DESIGN:. Retrospective cohort study. SETTING:. Large midwestern ECMO center. PATIENTS:. Adult patients receiving VV-ECMO. INTERVENTIONS:. Need for transfer to ECMO center following VV-ECMO cannulation. MEASUREMENTS AND MAIN RESULTS:. The study included 102 adult patients, 57% of which were cannulated at an outside institution prior to transfer. Of these, 60% were transported by ground, and the remainder were transported by air. Risk-adjusted logistic regression did not reveal any significant increase in odds for any complication or inhospital mortality between the groups based on location of cannulation or mode of transport. CONCLUSIONS:. This study supports the practice of interfacility ECMO transfer with no difference in outcomes or inhospital mortality based on institutional location of cannulation or mode of transport.

OBJECTIVES:. Determine the factors associated with mortality in venovenous extracorporeal membrane oxygenation (V-V ECMO) patients with COVID-19 infection and provide an updated report of clinical outcomes for patients treated with V-V ECMO for COVID-19 in Minnesota. DESIGN:. Multicenter prospective observational study. SETTING:. The four adult Extracorporeal Life Support Organization–certified Centers of Excellence in Minnesota. PATIENTS:. A total of 100 patients treated with V-V ECMO for COVID-19–associated acute respiratory distress syndrome (ARDS) from March 2020 to May 2021. INTERVENTIONS:. Not applicable. MEASUREMENTS AND MAIN RESULTS:. The primary outcome was 60-day survival for patients treated with V-V ECMO for COVID-19. Outcomes of patients treated from November 2020 to May 2021(cohort 2) were compared with data from a previous cohort of patients, collected from March 2020 to October 2020 (cohort 1). The data from both cohorts were merged into a single dataset (Combined Cohort). Survival on V-V ECMO due to COVID-19–associated ARDS significantly decreased after October 2020 (63% vs 41%; p = 0.026). The median interval from hospital admission to V-V ECMO cannulation was significantly associated with 60-day mortality (10 d [6–14 d] in nonsurvivors vs 7 d [4–9 d] in survivors; p = 0.001) in the Combined Cohort and was also significantly longer in cohort 2 than cohort 1 (10 d [7–14 d] vs 6 d [4–10 d]; p < 0.001). In the Combined Cohort, the 60-day survival for patients who did not receive steroids was 86% (n = 12) versus 45% (n = 39) for patients who received at least one dose of steroids (p = 0.005). CONCLUSIONS:. There was a significant increase in mortality for patients treated with V-V ECMO for COVID-19–associated ARDS in cohort 2 compared with cohort 1. Further research is required to determine the cause of the worsening trend in mortality.

Background. In this study, we evaluate the previously reported novel Minnesota Score for association with in-hospital mortality and allocation of venovenous extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome with or without SARS-CoV-2 pneumonia. Methods. This was a retrospective cohort study across four extracorporeal membrane oxygenation centers in Minnesota. Logistic regression was used to assess the relationship between the scores and in-hospital mortality, duration of ECMO cannulation, and discharge disposition. Priority groups were established statistically by maximizing the sum of sensitivity and specificity and compared to the previous qualitatively established priority groups. Results. Of 124 patients included in the study, 38% were treated for COVID-19 acute respiratory distress syndrome. The median age was 48 years, and 73% were male. The in-hospital mortality rate was 38%. The Minnesota Score was significantly associated with in-hospital mortality only (OR 1.13, p=0.02). Statistically determined cut points were similar to qualitative cut points. SARS-CoV-2 status did not change the findings. Conclusions. In our patient cohort, the Minnesota Score is associated with increased mortality. With further validation, proposed priority groups could be utilized for allocation of ECMO in times of increasing scarcity.

In the most severe cases, novel coronavirus (SARS-CoV-2) infection leads to Acute Respiratory Distress Syndrome which may be refractory to standard medical interventions including mechanical ventilation. There are growing reports of the use of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in these cases. A subset of critically ill COVID-19 patients develops cardiomyopathy as well, manifested by cardiogenic shock with reduced ejection fraction, dysrhythmias, and subsequent increase in mortality. One strategy for managing ARDS with an element of cardiogenic shock is venoarteriovenous (VAV) ECMO. Less than 1% of the cases in the worldwide ELSO COVID-19 database employed any form of hybrid cannulation. To date, there has only been one reported case of patient salvage with arterial or partial arterial support. We present a case that demonstrates the potential role of VAV ECMO in the case of concomitant severe ARDS with cardiomyopathy in the setting of COVID-19 infection.

In this article, we give a presentation of the longitudinal research program Individual Development and Adaptation (IDA) that can be helpful as a template for researchers considering to launch their own longitudinal studies, and that opens the door to IDA for researchers looking for suitable data to be analyzed within their own project or in collaboration with IDA. We also introduce the holistic-interactionistic theoretical framework of IDA and the associated person-oriented approach – an approach that is especially suited for analyzing the rich IDA data set with its broad coverage of different areas of adjustment and related factors. The paper provides an overview of the essential features of the IDA database, as well as of ongoing and planned IDA research.

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This article concerns the interpretation and construction of measurements for single observational units, including the crea-tion of scales or indexes to improve the quality of the measurements. The focus is on the individual as the observational unit in psychology, but to present a broader perspective related measurement issues in official statistics are also discussed. It is concluded that when individual measurements are to be interpreted, measurement precision must be given priority and taken into account in the research design. Unfortunately, most measures in psychology are not highly reliable, and examples are given demonstrating that such measures do not normally allow the researcher to make inferences about single individuals. Methods for testing questionnaires in a cognitive laboratory that have been developed within survey research can provide useful tools to increase both reliability and validity of single questions/items.

The purpose is to discuss and exemplify how a typological approach could be designed for studying phenomena believed to be best understood within a person-oriented theoretical framework. The focus is mainly restricted to the case of studying the typological structure of a sample at a single point in time, and restricted to analyzing variable profiles where each variable has a “negative” and “positive” endpoint. An artificial data set and an empirical data set were analyzed using two different methodological approaches, one more explorative (using LICUR, a cluster analysis-based procedure) and one more model-based (using the MCLUST procedure). For the artificial data set, the LICUR procedure was successful in finding the true classification structure but the MCLUST procedure performed surprisingly badly. For the empirical data set, both procedures produced rather similar solutions and they showed moderate validity. However, the LICUR solution appeared to be slightly superior. It was argued that applying a sound classification methodology and carefully validating the resulting classifications are extremely important, even more so in a developmental context. It was also argued that, in a number of situations, a more explorative approach could be more useful than a standard model-based one.

A short overview of the person-oriented approach is given as a guide to the researcher interested in carrying out person-oriented research. Theoretical, methodological, and practical considerations of the approach are discussed. First, some historical roots are traced, followed by a description of the holisticinteractionistic research paradigm, which provided the general framework for the development of the modern person-oriented approach. The approach has both a theoretical and a methodological facet and after presenting its key theoretical tenets, an overview is given of some common person-oriented methods. Central to the person-oriented approach is a system view with its components together forming a pattern regarded as indivisible. This pattern should be understood and studied as a whole, not broken up into pieces (variables) that are studied as separate entities. Hence, usually methodological tools are used by which whole patterns are analysed (e.g. cluster analysis). An empirical example is given where the pattern development of school grades is studied.

Lühike ülevaade indiviidile suunatud käsitlusviisist (person-oriented approach) koostati juhendmaterjaliks selle meetodi kasutamisest huvitatud uurijatele. Artiklis arutletakse meetodi teoreetiliste, metodoloogiliste ja praktiliste kaalutluste üle. Esiteks osutatakse mõningatele ajaloolistele juurtele. Sellele järgneb lühiülevaade holistlik-interaktsioonilisest uurimisparadigmast, mis moodustab indiviidikeskse käsitlusviisi üldise raami. Sellel käsitlusviisil on olemas nii teoreetiline kui ka metodoloogiline pool. Peale peamiste teoreetiliste tõekspidamiste tutvustatakse ka enam levinud indiviidikeskseid meetodeid. Indiviidile suunatud käsitlusviisi tuumaks on süsteemne vaade, mille kohaselt moodustavad süsteemi komponendid mustri, mida võiks pidada jagamatuks. Seda mustrit tuleks mõista ja uurida ühe tervikuna, mitte jagada tükkideks (variaabliteks/muutujateks), et neid tükke seejärel eraldiseisvate ühikutena uurida. Seega kasutatakse selliseid metodoloogilisi vahendeid, mis võimaldavad analüüsida tervikut (nt klasteranalüüs). Samuti esitatakse empiiriline näide koolihinnete arengumustrite uurimise kohta. Full text

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The paper focuses on the internal validity of clustering solutions. The “goodness” of a cluster structure can be judged by means of different cluster quality coefficient (QC) measures, such as the percentage of explained variance, the point-biserial correlation, the Silhouette coefficient, etc. The paper presents the most commonly used QCs occurring in well-known statistical program packages, and we have strived to make the presentation as non technical as possible to make it accessible to the applied researcher. The focus is on QCs useful in person-oriented research. Based on simulated data with independent variables, the paper shows that QCs can be strongly influenced by the number of clusters and the number of input variables, and that the value of a QC can be fairly high even in the absence of any real cluster structure. When evaluating the internal validity, it is helpful to relate the QCs of a clustering solution to those obtained in parallel analyses of random data. We also introduce a new type of QC, measuring the relative improvement (MORI) of a QC obtained for a certain clustering solution relative to the corresponding QC based on a relevant type of random data.

A good model of developmental phenomena should not only “explain” the data in the sense that the model is not falsified by the data but it should also be built on the basic theoretical assumptions about the process under study. This is often not the case when standard statistical models are applied to developmental data. An alternative is then to apply nonlinear dynamical system modeling. This approach is followed in the article and it is illustrated by a provisional model of the development of boys’ problem behavior between the ages 10 and 13. The underlying interactionistic theory of development was mirrored in a nonlinear model that predicted outcomes marginally better than a standard regression model. It is pointed out in the article that it might be possible to use nonlinear dynamic system modeling also in contexts where data are available only from a few measurement occasions.

This is a commentary to an article published by Brett Laursen in the first issue of the Journal for Person-Oriented Research where he wrote about his personal experiences with the person-oriented approach (Laursen, 2015). He discussed several sources of confusion with the approach and pointed to the importance of identifying areas of miscommunication that need to be addressed. Sources of confusion included the comparatively modest impact of the approach on mainstream research, terminological confusion, technical obstacles, and unclarity about what new knowledge is produced by the approach. These sources are briefly discussed and it is pointed out that the confusion is only partly due to miscommunication. It is true that those of us responsible for developing and advocating the approach have a communication problem with the broader scientific community that needs to be addressed - but Laursen´s confusion also points to challenges for the person-oriented approach in theory formulation and methodology development. Finally, it is urged that, when writing a paper using the person-oriented approach, the researcher should pay attention to Laursen´s sources of confusion and strive for clarity.

With the publication of this new issue of the Journal for Person-Oriented Research (JPOR), we are happy to acknowledge that the launching of this new journal has met a positive response, and that it is already expanding in several directions.The JPOR obviously seems to fill a gap in the existing range of journals devoted to the advancement of psychological science.

This first issue of Journal for Person-Oriented Research is a special issue devoted to the presentation of person-oriented approaches taken by leading researchers in the area. A prototypic person-oriented approach has three characteristics: (1) A pattern focus, (2) A focus on the individual, and (3) A process focus. The approach includes a theoretical framework, based on the holistic-interactionistic research paradigm, and it usually implies using methods for studying individual development, particularly subject-specific methods, and methods for studying patterns of information as undivided “wholes”. Four papers in this special issue are theory-oriented, dealing with historical roots of the approach, implications of a person-oriented theory for the methodology applied in empirical research, and discussing conceptual issues, including definitions of terms and communalities and differences of a person-oriented approach to standard approaches. The next three articles concern the use of various forms of a multi-level approach that points to promising ways for further development of the person-oriented approach. In the penultimate article, a statistical package for person-oriented analysis (ROPstat) is introduced. In the last article, a dynamic systems approach is presented for studying adaptive equilibrium regulation that separates forces working at a short and a long timescale.

ROPstat is a wide scope statistical program package which offers specialties in three domains: 1) robust techniques, 2) ordinal analyses, and 3) pattern and person oriented methods. Many of them are not available in other common statistical softwares. In the present paper, first the general features and the main structure of ROPstat are briefly outlined, followed by a more detailed summary of pattern-oriented methods (detecting and imputing missing values, residual case identification, different types of classifications, post-analyses after classifications, etc.). In the last section we present some selected person-oriented scientific questions and show with real-life research data how they can be analyzed using ROPstat.

Although Kaposi's sarcoma (KS) gene expression profile is closer to lymphatic (LEC) rather than blood vascular endothelial cells (BEC), uncertainty still surrounds the cellular origin of KS. To follow KS progression from early to late (nodular) stage, and characterize the molecular fingerprinting associated with each stage, gene arrays were used to compare gene expression profile of 9 skin samples of classic KS (4 Early, 2 Mixed, and 3 Nodular CKS samples) to 4 normal samples. Results for selected genes were validated by Real-time (RT) PCR and immunohistochemistry. Genes regulating immune and defense responses, angiogenesis, apoptosis and proliferation were differentially expressed in different KS stages compared to normal skin. Hierarchical clustering separated normal skin from KS with a clear gradient from early to nodular KS lesions. The gene expression level of endothelium markers, metalloproteinases, angiogenic factors and chemokines, gradually increased from normal through all KS stages. The expression of LEC genes highly increased from early to nodular KS. In the initiation phase we noticed a higher expression of growth factors, as compared to progressive stages. LEC and BEC markers co-exist in “KS expression signature”, although the LEC signature prevailed. Our results also show a complex environment of inflammatory cells and chemokines during KS evolution. A pathogenic hypothesis where cellular hyperproliferation is driven by local expression of chemokines and growth factors without clonal expansion of cells is suggested.

Neuroimaging studies in late life depression have reported decreased structural integrity of white matter tracts in the prefrontal cortex. Functional studies have identified changes in functional connectivity among several key areas involved in mood regulation. Few studies have combined structural and functional imaging. In this study we sought to examine the relationship between the uncinate fasciculus, a key fronto-temporal tract and resting state functional connectivity between the ventral prefrontal cortex ((PFC) and limbic and striatal areas.The sample consisted of 24 older patients remitted from unipolar major depression. Each participant had a magnetic resonance imaging brain scan using standardized protocols to obtain both diffusion tensor imaging and resting state functional connectivity data. Our statistical approach compared structural integrity of the uncinate fasciculus and functional connectivity data.We found positive correlations between left uncinate fasciculus (UF) fractional anisotropy (FA) and resting state functional connectivity (rsFC) between the left ventrolateral PFC and left amygdala and between the left ventrolateral PFC and the left hippocampus. In addition, we found a significant negative correlation between left ventromedial PFC-caudate rsFC and left UF FA. The right UF FA did not correlate with any of the seed region based connectivity.These results support the notion that resting state functional connectivity reflects structural integrity, since the ventral PFC is structurally connected to temporal regions by the UF. Future studies should include larger samples of patients and healthy comparison subjects in which both resting state and task-based functional connectivity are examined.