Wrestling With Issues in Scale Development Using Joint Latent Variable Methods

Many applications of biomedical science involve unobservable constructs, from measurement of health states to severity of complex diseases. In this dissertation I utilize joint latent variable methods to combine item selection and validation to identify significant items in a symptom scale and determine how these symptoms relate to gold standard diagnostic measures. Joint latent variable models eliminate bias inherent in traditional two-stage methods and provide a global test of the association between the underlying construct and a clinical measure. In Chapter 1, a review of latent variable methods for multivariate outcomes is provided. Chapter 2 proposes a Multiple Indicator Multiple Cause (MIMIC) model to perform item reduction and validation simultaneously. A modified Score test for individual factor loadings in the MIMIC model is derived. The methods are motivated by an example from a premenstrual syndrome (PMS) clinical trial in which one objective was to determine a reduced number of core symptoms in the diagnosis of severe PMS and to compare patient-reported symptom information to a clinician-rated gold standard diagnostic measure. Chapter 3 applies an extension to the MIMIC model to patient-reported outcomes (PROs) from the Physical Activity and Lymphedema (PAL) clinical trial. PROs are a potentially less expensive and time-consuming measure of diagnosis than some clinical measures. An extension of the MIMIC model for ordered categorical outcomes determines which symptoms are important indicators of lymphedema and how these symptoms compare to clinical endpoints. Finally, in Chapter 4, a multivariate zero-inflated proportional odds (MZIPO) model is proposed to account for excess symptom non-response at baseline. This model adds a latent class component to the traditional MIMIC model. The MZIPO model is applied to the PAL data to obtain more accurate estimates of the latent construct and its association with current measures of lymphedema severity

Measuring Cross-Cultural Supernatural Beliefs with Self- and Peer-Reports

Despite claims about the universality of religious belief, whether religiosity scales have the same meaning when administered inter-subjectively-or translated and applied cross-culturally-is currently unknown. Using the recent "Supernatural Belief Scale" (SBS), we present a primer on how to verify the strong assumptions of measurement invariance required in research on religion. A comparison of two independent samples, Croatians and New Zealanders, showed that, despite a sophisticated psychometric model, measurement invariance could be demonstrated for the SBS except for two noninvariant intercepts. We present a new approach for inspecting measurement invariance across self- and peer-reports as two dependent samples. Although supernatural beliefs may be hard to observe in others, the measurement model was fully invariant for Croatians and their nominated peers. The results not only establish, for the first time, a valid measure of religious supernatural belief across two groups of different language and culture, but also demonstrate a general invariance test for distinguishable dyad members nested within the same targets. More effort needs to be made to design and validate cross-culturally applicable measures of religiosity

Toxic effects of indocyanine green, infracyanine green, and trypan blue on the human retinal pigmented epithelium

Background: Indocyanine green, infracyanine green, and trypan blue are frequently used as aids to visualize structures removed during vitreoretinal surgery. But they may have toxic effects on the retina. We therefore compared the acute and chronic toxicities of these stains on cultured human retinal pigmented epithelial (RPE) cells using clinically relevant concentrations and an identical experimental setup for each agent. Methods: Monolayers of RPE cells were incubated with various concentrations of indocyanine green, infracyanine green (each at 0.005%, 0.05%, and 0.5%) or trypan blue (0.05%, 0.06%, 0.1%, 0.15%, and 0.5%) for 5min (acute exposure) or 6 days (chronic exposure). Using the propidium iodide assay, acute cytotoxicity was monitored at 15-min intervals for up to 3h. Chronic cytotoxicity was assessed by monitoring cell calcein esterase activity, cell proliferation, and cell morphology (viability) after 6 days of exposure. Results: Indocyanine and infracyanine green induced acute and chronic toxicities at a concentration above 0.05%. Trypan blue evoked no acute toxicity, but it was chronically cytotoxic at all tested concentrations. Conclusions: Despite thorough rinsing after application, significant amounts of the not sufficiently water soluble indocyanine and infracyanine green are retained after surgery by the eye. Trypan blue, being more water-soluble than ICG, is probably retained to the least degree. This circumstance is fortunate given that trypan blue exhibits a chronic cytotoxicity comparable to ICG at all clinically relevant concentrations. During vitrectomy, surgeons should aim to expose retinal tissue to only low concentrations of these stains and for as short a period as possibl

Antarctic Supraglacial Lake Identification Using Landsat-8 Image Classification

Surface meltwater generated on ice shelves fringing the Antarctic Ice Sheet can drive ice-shelf collapse, leading to ice sheet mass loss and contributing to global sea level rise. A quantitative assessment of supraglacial lake evolution is required to understand the influence of Antarctic surface meltwater on ice-sheet and ice-shelf stability. Cloud computing platforms have made the required remote sensing analysis computationally trivial, yet a careful evaluation of image processing techniques for pan-Antarctic lake mapping has yet to be performed. This work paves the way for automating lake identification at a continental scale throughout the satellite observational record via a thorough methodological analysis. We deploy a suite of different trained supervised classifiers to map and quantify supraglacial lake areas from multispectral Landsat-8 scenes, using training data generated via manual interpretation of the results from k-means clustering. Best results are obtained using training datasets that comprise spectrally diverse unsupervised clusters from multiple regions and that include rock and cloud shadow classes. We successfully apply our trained supervised classifiers across two ice shelves with different supraglacial lake characteristics above a threshold sun elevation of 20°, achieving classification accuracies of over 90% when compared to manually generated validation datasets. The application of our trained classifiers produces a seasonal pattern of lake evolution. Cloud shadowed areas hinder large-scale application of our classifiers, as in previous work. Our results show that caution is required before deploying ‘off the shelf’ algorithms for lake mapping in Antarctica, and suggest that careful scrutiny of training data and desired output classes is essential for accurate results. Our supervised classification technique provides an alternative and independent method of lake identification to inform the development of a continent-wide supraglacial lake mapping product

CO\u3csub\u3e2\u3c/sub\u3e and tectonic controls on Antarctic climate and ice-sheet evolution in the mid-Miocene

Antarctic ice sheet and climate evolution during the mid-Miocene has direct relevance for understanding ice sheet (in)stability and the long-term response to elevated atmospheric CO2 in the future. Geologic records reconstruct major fluctuations in the volume and extent of marine and terrestrial ice during the mid-Miocene, revealing a dynamic Antarctic ice-sheet response to past climatic variations. We use an ensemble of climate – ice sheet – vegetation model simulations spanning a range of CO2 concentrations, Transantarctic Mountain uplift scenarios, and glacial/interglacial climatic conditions to identify climate and ice-sheet conditions consistent with Antarctic mid-Miocene terrestrial and marine geological records. We explore climatic variability at both continental and regional scales, focusing specifically on Victoria Land and Wilkes Land Basin regions using a high-resolution nested climate model over these domains. We find that peak warmth during the Miocene Climate Optimum is characterized by a thick terrestrial ice sheet receded from the coastline under high CO2 concentrations. During the Middle Miocene Climate Transition, CO2 episodically dropped below a threshold value for marine-based ice expansion. Comparison of model results with geologic data support ongoing Transantarctic Mountain uplift throughout the mid-Miocene. Modeled ice sheet dynamics over the Wilkes Land Basin were highly sensitive to CO2 concentrations. This work provides a continental-wide context for localized geologic paleoclimate and vegetation records, integrating multiple datasets to reconstruct snapshots of ice sheet and climatic conditions during a pivotal period in Earth\u27s history

The recording, reporting, and use of school attendance data by school personnel in The Netherlands: toe the line or take a new path?

Research signals the importance of promptly identifying and responding to emerging absenteeism, to prevent severe and chronic absenteeism. Prompt identification and response relies upon a good system for recording, reporting, and using data related to students’ school attendance and absence. The current article provides an overview of law, policy, and practice in the Netherlands regarding the recording, reporting, and use of school attendance data. We then consider the ways in which current law, policy, and practice help and hinder the work of school personnel as they endeavour to promote attendance and reduce absenteeism. Thereafter, we propose modifications to current policy and practice that could enhance the prompt identification and response to emerging absenteeism. When school personnel have easy access to reliable attendance data, and when they become accustomed to using the data to inform their work to promote attendance and respond to absenteeism, they are in a stronger position to support positive developmental outcomes among young people.Pathways through Adolescenc

Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice

Background: In recent years, there has been increasing scientific interest into the effects and pharmacology of serotonergic hallucinogens. While a large amount of experimental work has been conducted to characterize the behavioral response to hallucinogens in rodents, there has been little systematic investigation of mescaline and its analogs. The hallucinogenic potency of mescaline is increased by α-methylation and by homologation of the 4-methoxy group but it not clear whether these structural modifications have similar effects on the activity of mescaline in rodent models. Methods: In the present study, the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of mescaline and several analogs in C57BL/6J mice. HTR experiments were conducted with mescaline, escaline (4-ethoxy-3,5-dimethoxyphenylethylamine) and proscaline (3,5-dimethoxy-4-propoxyphenylethylamine), their α-methyl homologues TMA (3,4,5-trimethoxy¬amphetamine), 3C-E (4-ethoxy-3,5-dimethoxyamphetamine) and 3C-P (3,5-dimethoxy-4-propoxy-amphetamine), and the 2,4,5-substituted regioisomers TMA-2 (2,4,5-trimethoxy¬amphetamine), MEM (4-ethoxy-2,5-dimethoxyamphetamine) and MPM (2,5-dimethoxy-4-propoxyamphetamine). Results: TMA induced the HTR and was twice as potent as mescaline. For both mescaline and TMA, replacing the 4-methoxy substituent with an ethoxy or propoxy group increased potency in the HTR assay. By contrast, although TMA-2 also induced the HTR with twice the potency of mescaline, potency was not altered by homologation of the 4-alkoxy group in TMA-2. Conclusions: The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. These findings are consistent with evidence that 2,4,5- and 3,4,5-substituted phenylalkylamine hallucinogens exhibit distinct structure-activity relationships. These results provide additional evidence that the HTR assay can be used to investigate the SAR of serotonergic hallucinogens

Comparison of the behavioral responses induced by phenylalkylamine hallucinogens and their tetrahydrobenzodifuran (“FLY”) and benzodifuran (“DragonFLY”) analogs

In recent years, rigid analogues of phenylalkylamine hallucinogens have appeared as recreational drugs. Examples include 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b′]difuran-4-yl)ethan-1-amine (2C-B-FLY) and 1-(8-bromobenzo[1,2-b;4,5-b’]difuran-4-yl)-2-aminopropane (Bromo-DragonFLY, DOB-DFLY). Although some rigid compounds such as DOB-DFLY reportedly have higher potency than their non-rigid counterparts, it is not clear whether the same is true for 2C-B-FLY and other tetrahydrobenzofurans. In the present study, the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of 2,5-dimethoxy-4-bromoamphetamine (DOB) and its α-desmethyl homologue 2,5-dimethoxy-4-bromophenethylamine (2C-B), as well as their benzodifuranyl and tetrahydrobenzodifuranyl analogs, in C57BL/6J mice. DOB (ED50 = 0.75 µmol/kg) and 2C-B (ED50 = 2.43 µmol/kg) induced the HTR. The benzodifurans DOB-DFLY (ED50 = 0.20 µmol/kg) and 2C-B-DFLY (ED50 = 1.07 µmol/kg) were also active and had significantly higher potency than DOB and 2C-B, respectively. The tetrahydrobenzodifurans DOB-FLY (ED50 = 0.67 µmol/kg) and 2C-B-FLY (ED50 = 1.79 µmol/kg), by contrast, were approximately equipotent with their non-rigid counterparts. Three novel tetrahydrobenzodifurans, 2C-I-FLY (ED50 = 5.12 µmol/kg), 2C-E-FLY (ED50 = 2.10 µmol/kg) and 2C-EF-FLY (ED50 = 4.37 µmol/kg), were also active in the HTR assay but had relatively low potency. In summary, the in vivo potency of 2,5-dimethoxyphenylalkylamines is enhanced when the 2- and 5-methoxy groups are incorporated into aromatic furan rings, whereas potency is not altered if the methoxy groups are incorporated into dihydrofuran rings. Potency was also increased in compounds containing an α-methyl group. The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. The unusually high potency of DOB-DFLY is probably linked to the presence of two structural features (a benzodifuran nucleus and an α-methyl group) known to enhance the potency of phenylalkylamine hallucinogens

Age, puberty and attractiveness judgments in adolescents

Previous work has suggested that judgments of the attractiveness of some facial and vocal features change during adolescence. Here, over 70 Czech adolescents aged 12–14 made forced-choice attractivenessjudgments on adolescent faces manipulated in symmetry, averageness and femininity, and on adolescent opposite-sex voices manipulated in fundamental frequency (perceived as pitch), and completed questionnaires on pubertal development. Consistent with typical adult judgments, adolescents selected the symmetric, average and feminine male and female faces as more attractive significantly more often than the asymmetric, non-average and masculine faces respectively. Moreover, preferences for symmetric faces were positively associated with adolescents’ age and stage of pubertal development. Unexpectedly, voice pitch did not significantly influence adolescents’ attractivenessjudgments. Collectively, these findings present new evidence using refined methodology that adolescent development is related to variation in attractivenessjudgments