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Previous research on co-development has focused on modeling the relations at the group level; however, how individuals differ in co-development may provide important information as well. Recent work has used vector plots to visually explore individual differences in co-development; however, these judgements were made based on visual inspection of a vector plot rather than the calculation of metrics. Here we propose two metrics that can be used to quantify co-development at the individual level: the co-development change ratio (CCR) and the angle of co-development metric (ACM). CCR provides information about the symmetry of development, examining whether an individual grew at the same pace in one skill relative to peers as compared to growth in the other skill relative to peers. ACM represents the relative amount and direction of change on each skill. This paper provides a tutorial on how to calculate and interpret these two metrics for quantifying co-development at the individual level., (© 2024. The Psychonomic Society, Inc.)

Purpose: We investigated and compared the outcomes from two standardized, norm-referenced screening assessments of language (i.e., Clinical Evaluation of Language Fundamentals Preschool-Second Edition [CELFP-2], Diagnostic Evaluation of Language Variation-Screening Test [DELV-ST]) with African American preschoolers whose spoken dialect differed from that of General American English (GAE). We (a) described preschoolers' performance on the CELFP-2 Core Language Index (CLI) and its subtests with consideration of degree of dialect variation (DVAR) observed, (b) investigated how the application of dialect-sensitive scoring modifications to the expressive morphology and syntax Word Structure (WS) subtest affected CELFP-2 CLI scores, and (c) evaluated the screening classification agreement rates between the DELV-ST and the CELFP-2 CLI., Method: African American preschoolers ( N = 284) completed the CELFP-2 CLI subtests (i.e., Sentence Structure, WS, Expressive Vocabulary) and the DELV-ST. Density of spoken dialect use was estimated with the DELV-ST Part I Language Variation Status, and percentage of DVAR was calculated. The CELFP-2 WS subtest was scored with and without dialect-sensitive scoring modifications., Results: Planned comparisons of CELFP-2 CLI performance indicated statistically significant differences in performance based on DELV-ST-determined degree of language variation groupings. Scoring modifications applied to the WS subtest increased subtest scaled scores and CLI composite standard scores. However, preschoolers who demonstrated strong variation from GAE continued to demonstrate significantly lower performance than preschoolers who demonstrated little to no language variation. Affected-status agreement rates between assessments (modified and unmodified CELFP-2 CLI scores and DELV-ST Part II Diagnostic Risk Status) were extremely low., Conclusions: The application of dialect-specific scoring modifications to standardized, norm-referenced assessments of language must be simultaneously viewed through the lenses of equity, practicality, and psychometry. The results of our multistage study reiterate the need for reliable methods of identifying risk for developmental language disorder within children who speak American English dialects other than GAE., Supplemental Material: https://doi.org/10.23641/asha.26017978.

Given English orthography's quasi-regular nature, applying common decoding rules to a word does not always result in a correct pronunciation matching the stored phonological form (e.g., the word tongue). To arrive at a correct pronunciation, developing readers must make the match between a decoded pronunciation and a word's correct pronunciation stored in memory. Developmentally, this matching process varies as a function of child skill (e.g., decoding, vocabulary) and word characteristics (e.g., spelling-to-pronunciation transparency, concreteness), with each being continuously distributed. Spelling-to-pronunciation transparency ratings represent a global measure of the ease of arriving at a word's correct pronunciation from its decoded pronunciation and in experimental studies has been shown to be a critical dimension in assessing the difficulty of a word for developing readers (e.g., Steacy et al., 2022a, 2022b). This study aimed to create a database of spelling-to-pronunciation transparency ratings for the 23,282 most frequently written English words, made available in the supplemental materials for future analyses. We asked adults to rate words' spelling-to-pronunciation transparency on a scale of 1-6 (1 = very easy to match, 6 = very difficult). Results of multiple regression analyses revealed variance in ratings to be unaccounted for by other word features, demonstrating the uniqueness of these ratings. Furthermore, words that are considered irregular, classified previously as strange, or contained at least one schwa received higher ratings, demonstrating strong associations between transparency and regularity. Lastly, these ratings significantly predicted both adult word naming time and child word reading accuracy above and beyond other word features known to predict reading., (© 2023. The Psychonomic Society, Inc.)

It is well documented that estrogens inhibit fluid intake. Most of this research, however, has focused on fluid intake in response to dipsogenic hormone and/or drug treatments in euhydrated rats. Additional research is needed to fully characterize the fluid intake effects of estradiol in response to true hypovolemia. As such, the goals of this series of experiments were to provide a detailed analysis of water intake in response to water deprivation in ovariectomized female rats treated with estradiol. In addition, these experiments also tested if activation of estrogen receptor alpha is sufficient to reduce water intake stimulated by water deprivation and tested for a role of glucagon like peptide-1 in the estrogenic control of water intake. As expected, estradiol reduced water intake in response to 24 and 48 h of water deprivation. The reduction in water intake was associated with a reduction in drinking burst number, with no change in drinking burst size. Pharmacological activation of estrogen receptor alpha reduced intake. Finally, estradiol-treatment caused a leftward shift in the behavioral dose response curve of exendin-4, the glucagon like peptide-1 agonist. While the highest dose of exendin-4 reduced 10 min intake in both oil and estradiol-treated rats, the intermediate dose only reduced intake in rats treated with estradiol. Together, this series of experiments extends previous research by providing a more thorough behavioral analysis of the anti-dipsogenic effect of estradiol in dehydrated rats, in addition to identifying the glucagon like peptide-1 system as a potential bioregulator involved in the underlying mechanisms by which estradiol reduces water intake in the female rat., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The lexical quality (LQ) hypothesis predicts that a skilled reader's lexicon will be inhabited by a range of low- to high-quality items, and the probability of representing a word with high quality varies as a function of person-level, word-level, and item-specific variables. These predictions were tested with spelling accuracy as a gauge of LQ., Method: Item-response based crossed random effects models explored simultaneous contributions of person-level (e.g., participant's decoding skill), word-level (e.g., word's transparency rating), item-specific (e.g., participant's familiarity with specific word), and person-by-word interaction predictors (e.g., decoding by transparency rating interaction) to the spelling of 25 commonly misspelled irregular English words in 61 undergraduate university students ( M = 19.4 years, 70.49% female, 39.34% Hispanic, 81.97% White)., Results: Substantial variance among individuals in item-level spelling accuracy was accounted for by person-level decoding skill; item-specific familiarity, proportion of schwas correctly represented, and correctly identifying the word from its mispronunciation; and an interaction of transparency rating by general decoding skill., Conclusions: Consistent with the LQ hypothesis, results suggest that one's ability to form a high-quality lexical representation of a given word depends on a complex combination of person-level abilities, word-level characteristics, item-specific experiences, and an interaction between person- and word-level influences.

Quasiregular orthographies such as English contain substantial ambiguities between orthography and phonology that force developing readers to acquire flexibility during decoding of unfamiliar words, a skill referred to as a "set for variability" (SfV). The ease with which a child can disambiguate the mismatch between the decoded form of a word and its actual lexical phonological form has been operationalized using the SfV mispronunciation task (e.g., the word wasp is pronounced to rhyme with clasp [i.e., /wæsp/] and the child must recognize the actual pronunciation of the word to be /wɒsp/). SfV has been shown to be a significant predictor of word reading variance. However, little is known about the relative strength of SfV as a predictor of word reading compared to other well-established predictors or the strength of this relationship in children with dyslexia. To address these questions, we administered the SfV task to a sample of grade 2-5 children ( N =489) along with other reading related measures. SfV accounted for 15% unique variance in word reading above and beyond other predictors, whereas phonological awareness (PA) accounted for only 1%. Dominance analysis indicated SfV is the most powerful predictor, demonstrating complete statistical dominance over other variables including PA. Quantile regression revealed SfV is a stronger predictor at lower levels of reading skill, indicating it may be an important predictor in students with dyslexia. Results suggest that SfV is a powerful and potentially highly sensitive predictor of early reading difficulties and, therefore, may be important for early identification and treatment of dyslexia.

Introduction: Although the fluid inhibitory effects of estradiol are well characterized, a dipsogenic role of the hormone was recently identified. In ovariectomized (OVX) rats, unstimulated water intake, in the absence of food, was increased after estradiol treatment., Methods: The goals for these experiments were to further characterize the fluid enhancing effects of estradiol by determining the estrogen receptor subtype mediating the dipsogenic effect, examining saline intake, and testing for a dipsogenic effect of estradiol in male rats., Results: Pharmacological activation of estrogen receptor beta (ERβ) increased water intake, in the absence of food, and was associated with changes in postingestive feedback signals. Surprisingly, activation of ERα reduced water intake even in the absence of food. A follow-up study demonstrated that when food was available, co-activation of ERα and ERβ reduced water intake, but when food was not available water intake was increased. In addition, in OVX rats, estradiol increased saline intake through changes in postingestive and orosensory feedback signals. Finally, although estradiol decreased water intake in male rats with access to food, estradiol had no effect on water intake in the absence of food., Conclusions: These results demonstrate that the dipsogenic effect is mediated by ERβ, the fluid enhancing effects of estradiol generalize to saline, and is limited to females, which implies that a feminized brain is necessary for estradiol to increase water intake. These findings will aid in guiding future studies focused on elucidating the neuronal mechanisms that allow estradiol to both increase and decrease fluid intake., (© 2023 S. Karger AG, Basel.)

Given the recent push for universal screening, it is important to take into account how well a screener identifies children at risk for reading problems as well as how screener and sample information contribute to this classification. Picking the best cut-point for a particular sample and screening goal can be challenging given that test manuals often report classification information for a specific cut-point and sample base rate which may not generalize to other samples. By assuming a bivariate normal distribution, it is possible to calculate all of the classification information for a screener based on the correlation between the screener and outcome, the cut-point on the outcome (i.e., the base rate in the sample), and the cut-point on the screener. We provide an example with empirical data to validate these estimation procedures. This information is the basis for a free online tool that provides classification information for a given correlation between screener and outcome and cut-points on each. Results show that the correlation between screener and outcome needs to be greater than .9 (higher than observed in practice) to obtain good classification. These findings are important for researchers, administrators, and practitioners because current screeners do not meet these requirements. Since a correlation is dependent on the reliability of the measures involved, we need screeners with better reliability and/or multiple measures to increase reliability. Additionally, we demonstrate the impact of base rate on positive predictive power and discuss how gated screening can be useful in samples with low base rates., (© 2022. The Author(s), under exclusive licence to The International Dyslexia Association.)

Herein, we introduce the first diphenylalanine dipeptide hydrogelator capped with the cinnamoyl functional group (Cin-L-F-L-F). We evaluate the effects of the cinnamoyl moiety on molecular self-assembly events and resultant physical properties of the hydrogel formed. In addition, we report our preliminary results of this dipeptide's cytotoxicity against glioblastoma (GBM) cancer cells.

Set for variability (SfV) is an oral language task which requires an individual to disambiguate the mismatch between the decoded form of an irregular word and its actual lexical pronunciation. For example, in the task, the word wasp is pronounced to rhyme with clasp (i.e., / wæsp /) and the individual must recognize the actual pronunciation of the word to be / wɒsp /. SfV has been shown to be a significant predictor of both item-specific and general word reading variance above and beyond that associated with phonemic awareness skill, letter-sound knowledge, and vocabulary skill. However, very little is known about the child characteristics and word features that affect SfV item performance. In this study we explored whether word features and child characteristics that involve phonology only are adequate to explain item-level variance in SfV performance or whether including predictors that involve the connection between phonology and orthography explain additional variance. To accomplish this we administered the SfV task ( N =75 items) to a sample of grade 2-5 children ( N =489) along with a battery of reading, reading related, and language measures. Results suggest that variance in SfV performance is uniquely accounted for by measures tapping phonological skill along with those capturing knowledge of phonology to orthography associations, but more so in children with better decoding skill. Additionally, word reading skill was found to moderate the influence of other predictors suggesting that how the task is approached may be impacted by word reading and decoding ability.

Purpose: The probability of a child reading a word correctly is influenced by both child skills and properties of the word. The purpose of this study was to investigate child-level skills (set for variability and vocabulary), word-level properties (concreteness), word structure (mono- vs. polymorphemic), and interactions between these properties and word structure within a comprehensive item-level model of complex word reading. This study is unique in that it purposely sampled both mono- and polymorphemic polysyllabic words., Method: A sample of African American ( n = 69) and Hispanic ( n =6) students in grades 2-5 ( n =75) read a set of mono- and polymorphemic polysyllabic words ( J =54). Item-level responses were modeled using cross-classified generalized random-effects models allowing variance to be partitioned between child and word while controlling for other important child factors and word features., Results: Set for variability and the interaction between concreteness and word structure (i.e., mono- vs. polymorphemic) were significant predictors. Higher probabilities of reading poly- over monomorphemic words were identified at lower levels of concreteness with the opposite at higher levels of concreteness., Conclusions: Results indicate important predictors at both the child- and word-level and support the importance of morphological structure for reading abstract polysyllabic words., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

The accuracy of certain internal consistency estimators have been questioned in recent years. The present study tests the accuracy of six reliability estimators (Cronbach's alpha, omega, omega hierarchical, Revelle's omega, and greatest lower bound) in 140 simulated conditions of unidimensional continuous data with uncorrelated errors with varying sample sizes, number of items, population reliabilities, and factor loadings. Estimators that have been proposed to replace alpha were compared with the performance of alpha as well as to each other. Estimates of reliability were shown to be affected by sample size, degree of violation of tau equivalence, population reliability, and number of items in a scale. Under the conditions simulated here, estimates quantified by alpha and omega yielded the most accurate reflection of population reliability values. A follow-up regression comparing alpha and omega revealed alpha to be more sensitive to degree of violation of tau equivalence, whereas omega was affected greater by sample size and number of items, especially when population reliability was low., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

The inhibitory effect of estradiol (E2) on water intake has been recognized for 50 years. Despite a rich literature describing this phenomenon, we report here a previously unidentified dipsogenic effect of E2 during states of low fluid intake. Our initial goal was to test the hypothesis that the anti-dipsogenic effect of E2 on unstimulated water intake is independent of its anorexigenic effect in female rats. In support of this hypothesis, water intake was reduced during estrus, compared to diestrus, when food was present or absent. Water intake was reduced by E2 in ovariectomized rats when food was available, demonstrating a causative role of E2. Surprisingly, however, when food was removed, resulting in a significant reduction in baseline water intake, E2 enhanced drinking. Accordingly, we next tested the effect of E2 on water intake after an acute suppression of intake induced by exendin-4. The initial rebound drinking was greater in E2-treated, compared to Oil-treated, rats. Finally, to reconcile conflicting reports regarding the effect of ovariectomy on water intake, we measured daily water and food intake, and body weight in ovariectomized and sham-operated rats. Predictably, ovariectomy significantly increased food intake and body weight, but only transiently increased water intake. Together these results provide further support for independent effects of E2 on the controls of water and food intake. More importantly, this report of bidirectional effects of E2 on water intake may lead to a paradigm shift, as it challenges the prevailing view that E2 effects on fluid intake are exclusively inhibitory., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Estradiol (E2) inhibits fluid intake in several species, which may help to defend fluid homeostasis by preventing excessive extracellular fluid volume. Although this phenomenon is well established using the rat model, it has only been studied directly in young adults. Because aging influences the neuronal sensitivity to E2 and the fluid intake effects of E2 are mediated in the brain, we tested the hypothesis that aging influences the fluid intake effects of E2 in female rats. To do so, we examined water and NaCl intake in addition to the pressor effect after central angiotensin II treatment in young (3-4 months), middle-aged (10-12 months), and old (16-18 months) ovariectomized rats treated with estradiol benzoate (EB). As expected, EB treatment reduced water and NaCl intake in young rats. EB treatment, however, did not reduce water intake in old rats, nor did it reduce NaCl intake in middle-aged or old rats. The ability of EB to reduce blood pressure was, in contrast, observed in all three age groups. Next, we also measured the gene expression of estrogen receptors (ERs) and the angiotensin type 1 receptor (AT1R) in the areas of the brain that control fluid balance. ERβ, G protein estrogen receptor (GPER), and AT1R were reduced in the paraventricular nucleus of the hypothalamus in middle-aged and old rats, compared to young rats. These results suggest the estrogenic control of fluid intake is modified by age. Older animals lost the fluid intake effects of E2, which correlated with decreased ER and AT1R expression in the hypothalamus., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Developmental studies examining relations between word reading (WR) and decoding in typical and dyslexic populations routinely cut the reading distribution to form distinct groups. However, dichotomizing continuous variables to study development is problematic for multiple reasons. Instead, we modeled and visualized the parallel growth of WR and nonword reading (NWR) factor scores longitudinally in a Grade 1-4 developmental sample (N = 588). The results indicate that while WR and NWR growth factors are highly related (r = .71), the relation between WR and NWR trajectories change as a function of initial WR. Results are interpreted within computational models of dyslexia in which children with dyslexia overfit orthography → phonology relations at the level of the word, limiting the development of sublexical representations needed to read nonwords., (© 2020 Society for Research in Child Development.)

The assumption that body weight is a predictor of fluid intake is often used as rationale for normalizing intake to body weight when examining sex differences in drinking behavior. Nonuniform application of this body weight correction likely contributes to discrepancies in the literature. We, however, previously demonstrated sex differences in the relationship between body weight and angiotensin II (AngII)-stimulated water intake. Only after a pharmacological dose of AngII did water intake correlate with body weight, and only in males. Here we investigated whether body weight correlated with fluid intake stimulated by additional dipsogenic agents in male and female rats. We found that intake stimulated by either water deprivation or furosemide correlated with body weight in male rats. We found no relationship between intake and body weight after water deprivation, furosemide treatment, or isoproterenol treatment in females, nor did we find a relationship between intake and body weight after hypertonic saline treatment in either males or females. Finally, we report that daily water intake correlated with body weight in females. This effect, however, is likely the result of a relationship between body weight and food intake because when food was absent or reduced, the correlation between body weight and intake disappeared. These results demonstrate that multiple factors need to be considered when determining the best way to compare fluid intake between males and females and provides insight to help explain the discrepancies in the literature regarding sex differences in fluid intake., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The COVID pandemic, which started on 11th March as per the World Health Organization, has resulted in a drastic change in health care delivery, including emergency services. Most health workers have deviated towards COVID care delivery; only a few were available for non-COVID conditions. All elective and non-essential services were postponed resulting in the increased burden of the emergency department. The emergency department had to provide essential emergency care with available staff without exposing them to the virus. Triaging of the patients was modified according to the needs., Methods: The statistics of the emergency department of this period (April and May 2020) are compared with the same period of previous years (2018-2019) with the number of patients, indications, and complications. The methods of triaging and preparation were discussed., Discussion: The number of patients admitted to the emergency department (ED) was low during the COVID pandemic. Nevertheless, they got admitted with complications due to delay in accessing the health care facility. Patients with diabetic foot ulcers were also presenting late, leading to an increased number of the forefoot and below knee amputations. In trauma, the emergency department has maintained the same death rate as previous years by giving great care. The indications for tracheostomy were worrisome because it would have been prevented if the patients presented early. Pediatric patients were also presented late, resulting in increased mortality. Some cancer patients also presented with a complication in the emergency department because of the postponement of elective surgeries., Conclusion: There is a delay in accessing the health care delivery for non-COVID conditions resulting in more amputations of limbs and resections of the bowel. So the type of care in the emergency department was changed due to atypical presentation and complicated cases. It is necessary to ensure the provision of high quality health care delivery to non-COVID patients also., Competing Interests: The authors declare that there is no conflict of interest., (© 2020 The Authors.)

How prevalent is dyslexia? A definitive answer to this question has been elusive because of the continuous distribution of reading performance and predictors of dyslexia and because of the heterogeneous nature of samples of poor readers. Samples of poor readers are a mixture of individuals whose reading is consistent with or expected based on their performance in other academic areas and in language, and individuals with dyslexia whose reading is not consistent with or expected based on their other performances. In the present article, we replicate and extend a new approach for determining the prevalence of dyslexia. Using model-based meta-analysis and simulation, three main results were found. First, the prevalence of dyslexia is better represented as a distribution that varies as a function of severity as opposed to any single-point estimate. Second, samples of poor readers will contain more expected poor readers than unexpected or dyslexic readers. Third, individuals with dyslexia can be found across the reading spectrum as opposed to only at the lower tail of reading performance. These results have implications for screening and identification, and for recruiting participants for scientific studies of dyslexia.

The distinctive features of the Arabic language and orthography offer opportunities to investigate multiple word characteristics at the item level. The aim of this paper was to model differences in word reading at the item level among 3rd grade native Arabic-speaking children (n = 303) using cross-classified generalized random-effects (CCGRE) analysis. The participants read 80 vowelized words that varied in multiple elements that may contribute to their decodability: number of letters, number of syllables, number of morphemes, ligaturing (connectivity), semantics (concrete vs. abstract), orthographic frequency, root type frequency, and part of speech. Morphological awareness (MA) was included as a person-level predictor. Results of individual models showed that MA, number of letters, number of syllables, number of morphemes, number of ligatures, orthographic frequency, and part of speech were significantly related to the probability of a correct response. However, when all predictors were entered simultaneously, only MA and number of morphemes remained significant. These results underscore the important role of morphology in the lexical structure of Arabic words and in Arabic word reading. Discussion focuses on the role of morphology in Arabic reading and the implications for intervention to improve word recognition in children learning to read Arabic.

The purpose of this study was to examine word learning efficiency in at-risk first grade students (N = 93) participating in a yearlong study evaluating a multicomponent intervention targeting word reading and decoding skills. As part of each intervention lesson, students participated in a 1 to 3-min sight word reading activity in which high-frequency words were read from a list until mastered, at which point the word dropped off the list. This study explored factors predicting the number of exposures required for item reading mastery (N = 145 words). Specifically, we explored how the number of word exposures required to reach mastery varied as a function of linguistic features of the words and cognitive characteristics of the students. Using item-level crossed-random effects models, we found students required an average of 5.65 exposures for mastery, with word features representing word length, vocabulary grade, and imageability being significant predictors of learning efficiency. We also found a significant interaction between pretest word reading skill and imageability of a word, with this semantic feature being especially important for the poorest readers. Results indicate that in the absence of typical word recognition skills, poor readers tend to rely on other sources of information to learn words, which tend to be related to the semantic features of words.

Dehydration impairs cognitive performance in humans and rodents, although studies in animal models are limited. Estrogens have both protective effects on fluid regulation and improve performance in certain cognitive tasks. We, therefore, tested whether sex and gonadal hormones influence object recognition memory during dehydration. Because past studies used fluid deprivation to induce dehydration, which is a mixture of intracellular and extracellular fluid loss, we tested the effects of osmotic (loss of intracellular fluid) and hypovolemic (loss of extracellular fluid) dehydration on object recognition memory. After training trials consisting of exposure to two identical objects, rats were either treated with hypertonic saline to induce osmotic dehydration, furosemide to induce hypovolemic dehydration, or received a control injection and then object recognition memory was tested by presenting the original and a novel object. After osmotic dehydration, regardless of group or treatment, all rats spent significantly more time investigating the novel object. After hypovolemic dehydration, regardless of treatment, both the males and estrous females spent significantly more time investigating the novel object. While the control-treated diestrous females also spent significantly more time investigating the novel object, the furosemide-treated diestrous females spent a similar amount of time investigating the novel and original object. Follow up studies determined that loss of ovarian hormones after ovariectomy, but not loss of testicular hormones after castration, resulted in impaired memory performance in the object recognition test after hypovolemic dehydration. This series of experiments provides evidence for a protective role of ovarian hormones on dehydration-induced memory impairments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite decades of research, it has been difficult to achieve consensus on a definition of common learning disabilities such as dyslexia. This lack of consensus represents a fundamental problem for the field. Our approach to addressing this issue is to use model-based meta-analyses and Bayesian models with informative priors to combine the results of a large number of studies for the purpose of yielding a more stable and well-supported conceptualization of reading disability. A prerequisite to implementing these models is establishing informative priors for dyslexia. We illustrate a new approach for doing so based on the known distribution of the difference between correlated variables, and use this distribution to determine the proportion of poor readers whose poor reading is unexpected (i.e., likely to be due to dyslexia) as opposed to expected., (© 2019 Wiley Periodicals, Inc.)

Circular dichroism (CD) spectroscopy has been used extensively for the investigation of the conformation and configuration of chiral molecules, but its use for evaluating the mode of self-assembly in soft materials has been limited. Herein, we report a protocol for the study of such materials by electronic CD spectroscopy using commercial/benchtop instruments and synchrotron radiation (SR) using the B23 beamline available at Diamond Light Source. The use of the B23 beamtime for SRCD was advantageous because of the unique enhanced spatial resolution achieved because of its highly collimated and small beamlight cross section (ca. 250 μm) and higher photon flux in the far UV region (175-250 nm) enhancing the signal-to-noise ratio relative to benchtop CD instruments. A set of low molecular weight (LMW) hydrogelators, comprising two Fmoc-protected enantiomeric monosaccharides and one Fmoc dipeptide (Fmoc-FF), were studied. The research focused on the optimization of sample preparation and handling, which then enabled the characterization of sample conformational homogeneity and thermal stability. CD spectroscopy, in combination with other spectroscopic techniques and microscopy, will allow a better insight into the self-assembly of chiral building blocks into higher order structural architectures., (© 2018 Wiley Periodicals, Inc.)

Unlike traditional media, social media systems often present information of different types from different kinds of contributors within a single message pane, a juxtaposition of potential influences that challenges traditional health communication processing. One type of social media system, question-and-answer advice systems, provides peers' answers to health-related questions, which yet other peers read and rate. Responses may appear good or bad, responders may claim expertise, and others' aggregated evaluations of an answer's usefulness may affect readers' judgments. An experiment explored how answer feasibility, expertise claims, and user-generated ratings affected readers' assessments of advice about anonymous HIV testing. Results extend the heuristic-systematic model of persuasion (Chaiken, 1980) and warranting theory (Walther & Parks, 2002). Information that is generally associated with both systematic and heuristic processes influenced readers' evaluations. Moreover, content-level cues affected judgments about message sources unexpectedly. When conflicting cues were present, cues with greater warranting value (consensus user-generated ratings) had greater influence on outcomes than less warranted cues (self-promoted expertise). Findings present a challenge to health professionals' concerns about the reliability of online health information systems.

A comprehensive understanding of the mechanisms of interaction between proteins or peptides and nanomaterials is crucial for the development of nanomaterial-based diagnostics and therapeutics. In this work, we systematically explored the interactions between citrate-capped gold nanoparticles (AuNPs) and islet amyloid polypeptide (IAPP), a 37-amino acid peptide hormone co-secreted with insulin from the pancreatic islet. We utilized diffusion-ordered spectroscopy, isothermal titration calorimetry, localized surface plasmon resonance spectroscopy, gel electrophoresis, atomic force microscopy, transmission electron microscopy (TEM), and molecular dynamics (MD) simulations to systematically elucidate the underlying mechanism of the IAPP-AuNP interactions. Because of the presence of a metal-binding sequence motif in the hydrophilic peptide domain, IAPP strongly interacts with the Au surface in both the monomeric and fibrillar states. Circular dichroism showed that AuNPs triggered the IAPP conformational transition from random coil to ordered structures (α-helix and β-sheet), and TEM imaging suggested the acceleration of IAPP fibrillation in the presence of AuNPs. MD simulations revealed that the IAPP-AuNP interactions were initiated by the N-terminal domain (IAPP residues 1-19), which subsequently induced a facet-dependent conformational change in IAPP. On a Au(111) surface, IAPP was unfolded and adsorbed directly onto the Au surface, while for the Au(100) surface, it interacted predominantly with the citrate adlayer and retained some helical conformation. The observed affinity of AuNPs for IAPP was further applied to reduce the level of peptide-induced lipid membrane disruption.

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and β-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1 H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na + , K + , Ag + ) but showed selectivity for divalent cations (Ca 2+ , Ba 2+ , Sr 2+ and Mg 2+ ). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca 2+ and Ba 2+ ), while 5-coordination is preferred for divalent cations with larger (Ba 2+ ) or smaller ionic radii (Mg 2+ ).

The aim of this study was to apply the fluorescence in situ hybridization (FISH) translocation assay in combination with chromosome painting of peripheral blood lymphocytes for retrospective biological dosimetry of Mayak nuclear power plant workers exposed chronically to external gamma radiation. These data were compared with physical dose estimates based on monitoring with badge dosimeters throughout each person's working life. Chromosome translocation yields for 94 workers of the Mayak production association were measured in three laboratories: Southern Urals Biophysics Institute, Leiden University Medical Center and the former Health Protection Agency of the UK (hereinafter Public Health England). The results of the study demonstrated that the FISH-based translocation assay in workers with prolonged (chronic) occupational gamma-ray exposure was a reliable biological dosimeter even many years after radiation exposure. Cytogenetic estimates of red bone marrow doses from external gamma rays were reasonably consistent with dose measurements based on film badge readings successfully validated in dosimetry system "Doses-2005" by FISH, within the bounds of the associated uncertainties.

Objectives: To evaluate the ability of prostate HistoScanning™ (PHS; Advanced Medical Diagnostics, Waterloo, Belgium) to detect, characterize and locally stage prostate cancer, by comparing it with transrectal ultrasonography (TRUS)-guided prostate biopsies, transperineal template prostate biopsies (TTBs) and whole-mount radical prostatectomy specimens., Subjects and Methods: Study 1. We recruited 24 patients awaiting standard 12-core TRUS-guided biopsies of the prostate to undergo PHS immediately beforehand. We compared PHS with the TRUS-guided biopsy results in terms of their ability to detect cancer within the whole prostate and to localize it to the correct side and to the correct region of the prostate. Lesions that were suspicious on PHS were biopsied separately. Study 2. We recruited 57 patients awaiting TTB to have PHS beforehand. We compared PHS with the TTB pathology results in terms of their ability to detect prostate cancer within the whole gland and to localize it to the correct side and to the correct sextant of the prostate. Study 3. We recruited 24 patients awaiting radical prostatectomy for localized prostate cancer to undergo preoperative PHS. We compared PHS with standardized pathological analysis of the whole-mount prostatectomy specimens in terms of their measurement of total tumour volume within the prostate, tumour volume within prostate sextants and volume of index lesions identified by PHS., Results: The PHS-targeted biopsies had an overall cancer detection rate of 38.1%, compared with 62.5% with standard TRUS-guided biopsies. The sensitivity and specificity of PHS for localizing tumour to the correct prostate sextant, compared with standard TRUS-guided biopsies, were 100 and 5.9%, respectively. The PHS-targeted biopsies had an overall cancer detection rate of 13.4% compared with 54.4% for standard TTB. PHS had a sensitivity and specificity for cancer detection in the posterior gland of 100 and 13%, respectively, and for the anterior gland, 6 and 82%, respectively. We found no correlation between total tumour volume estimates from PHS and radical prostatectomy pathology (Pearson correlation coefficient -0.096). Sensitivity and specificity of PHS for detecting tumour foci ≥0.2 mL in volume were 63 and 53%., Conclusions: These three independent studies in 105 patients suggest that PHS does not reliably identify and characterize prostate cancer in the routine clinical setting., (© 2013 The Authors. BJU International © 2013 BJU International.)

Isolation of microglia from CNS tissue is a powerful investigative tool used to study microglial biology ex vivo. The present method details a procedure for isolation of microglia from neonatal murine cortices by mechanical agitation with a rotary shaker. This microglia isolation method yields highly pure cortical microglia that exhibit morphological and functional characteristics indicative of quiescent microglia in normal, nonpathological conditions in vivo. This procedure also preserves the microglial immunophenotype and biochemical functionality as demonstrated by the induction of morphological changes, nuclear translocation of the p65 subunit of NF-κB (p65), and secretion of the hallmark proinflammatory cytokine, tumor necrosis factor-α (TNF-α), upon lipopolysaccharide (LPS) and Pam3CSK4 (Pam) challenges. Therefore, the present isolation procedure preserves the immunophenotype of both quiescent and activated microglia, providing an experimental method of investigating microglia biology in ex vivo conditions.

Piroxicam is a non-steroidal anti-inflammatory drug that is characterised by low solubility and high permeability. In order to improve the drug dissolution rate, the co-grinding method was used as an approach to prepare piroxicam co-ground in the carriers such as glucosamine hydrochloride. As, this amino sugar (glucosamine HCl) has been shown to decrease pain and improve mobility in osteoarthritis in joints, therefore, the incorporation of glucosamine in piroxicam formulations would be expected to offer additional benefits to patients. The effect of the order of grinding on the dissolution of piroxicam was also investigated. Co-ground drug and glucosamine were prepared in different ratios using a ball mill. The samples were then subjected to different grinding times. In order to investigate the effect of the grinding process on the dissolution behaviour of piroxicam, the drug was ground separately in the absence of glucosamine. Mixtures of ground piroxicam and unground D-glucosamine HCl were prepared. Physical mixtures of piroxicam and glucosamine were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FTIR, SEM, XRPD and DSC. These results showed that the presence of glucosamine HCl can increase dissolution rate of piroxicam compared to pure piroxicam. Generally, all dissolution profiles showed the fastest dissolution rate when ground piroxicam was mixed with unground glucosamine. This was closely followed by the co-grinding of piroxicam with glucosamine where lower grinding times showed the fastest dissolution. The solid state studies showed that the grinding of piroxicam for longer times had no effect on polymorphic form of piroxicam, whereas mixtures of piroxicam-glucosamine ground for longer times (60 min) converted piroxicam polymorph II to polymorph I., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This paper presents the results of a feasibility cytogenetic study using the fluorescence in situ hybridization (FISH) translocation assay for residents of villages located on the Techa River (Southern Urals, Russia) contaminated with liquid radioactive wastes from the Mayak plutonium facility in 1949-1956. The study was conducted with two groups of donors that differed in their main pathways of exposure. The first group comprised 18 residents of the middle Techa region who were exposed predominantly from ingestion of radionuclides (mostly (89,90)Sr) via the river water and local foodstuffs. The second group included 20 residents of Metlino, the closest village to the site of releases, who were exposed to external γ radiation from the contaminated river bank and exposed internally from dietary intake of radionuclides. A significant linear dependence between the radiation-induced translocation frequency and individual red bone marrow dose from incorporated (89,90)Sr, calculated with the Techa River Dosimetry System (TRDS), was found in the first group of donors. This allowed us to take the contribution of (89,90)Sr to the total radiation-induced translocation frequency into account for the second group of donors and to analyze translocations resulting from external γ-ray exposure. Individual doses from external exposure derived from the corrected translocation frequency for the second group of donors (Metlino residents), using a linear dose-response coefficient of 0.015 translocation/cell/Gy recommended by Edwards et al. in 2005, were shown to vary up to 2.1 Gy, with an average value of 0.48 Gy, which was in agreement with TRDS-based external dose estimates for Metlino residents.

The solution-phase synthesis and cyclisation of three α,β-peptoid octamers with differing side chain patterns is reported. One of these, compound C, showed a significantly greater resolution by NMR relative to the other two structurally related octamers. This observation was studied in detail by circular dichroism at a synchrotron light source to facilitate the correlation between the side chain patterns and conformational preference of these three peptoids. The X-ray crystal structure of cyclic octamer C, the first high-resolution structure for the α,β-peptoid backbone, was also obtained from methanol. Combined solid- and solution-phase studies allowed the identification of the N-2-(benzyloxy)ethyl side chain on the β-residue of the heterogeneous backbone as a key structural feature driving the increased conformational stability for octamer C.

This article describes the efficient synthesis of the first generation of branched sugar amino acid (SAA) oligomers in solution phase via two main routes: by the use of a standard coupling reagent and via the use of active ester intermediates. Benzyl-protected dimeric carbopeptoid and methyl-protected dimeric and tetrameric, hexameric and octameric carbopeptoids were obtained from a branched δ-3,5-trans-tetrahydrofuran (THF) SAA and methyl-protected dimeric and tetrameric carbopeptoids were synthesised from a branched δ-3,5-cis-THF SAA. These systems are of interest because of their potential to display foldameric properties reminiscent of those observed in α-peptides and proteins. Amongst their many uses, foldamers provide simpler models in the study of the factors which induce the folding and unfolding of proteins and, ultimately, potential insights into their functioning.

Objectives: To evaluate the medical professionals and medical students perceived usefulness of an emergency medical card (EMC) and a continuity of care (CoC) report, in enhancing CoC., Methods: The study reviewers included medical professionals from outpatient clinics at Intermountain Healthcare and fourth-year medical students from the University of Utah. Three cases we randomly extracted from a database of patients who had added new care information at the time. EMCs and CoC reports were populated for the cases, and information then de-identified. Using patient information in the electronic medical record (EMR), reviewers evaluated if the EMR information was adequate to support medical decisions made on the patient's diagnosis, medications, laboratory tests, and disposition. The reviewer assessed if the EMC and CoC report information would influence the medical decisions made. An online survey was used to assess the reviewers' perception on the usefulness of the two documents., Results: On average, 94% of the reviewers perceived the EMC to be useful in enhancing medical decision making at the point of care, and 74% found the CoC report to be useful. More specifically, the two documents were found to be useful in decreasing encounter time (100% each), increasing overall knowledge of healthcare providers (100% each), influencing decision on the treatment (94% each), and new laboratory test orders (87% and 90%, respectively)., Conclusions: The EMC and CoC report were found to be useful methods for transporting patient healthcare information across the healthcare continuum. The documents were found more specifically to be useful for effective decision making, improving efficiency and quality of care, at the point of care., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To compare the development of intestinal adenomas following neutron and X-ray exposure of Apc(Min/+) mice (Apc - adenomatous polyposis coli; Min - multiple intestinal neoplasia)., Materials and Methods: Adult mice were exposed to acute doses of X-rays or fission neutrons. Tumour counting was undertaken 200 days later and samples were taken for Loss of Heterozygosity (LOH) analysis., Results: Tumour numbers (adenomas and microadenomas) increased by 1.4-fold, 1.7-fold, 2.7-fold and 9-fold, after 0.5, 1, 2 and 5 Gy X-rays, respectively, and by 2.4-fold and 5.7-fold, after 0.5 and 1 Gy fission neutrons, respectively. LOH analysis of tumours from neutron-exposed mice showed that 63% had lost Apc and 90% (cf. 53% in controls) had lost D18mit84, a marker for Epb4.1l4a/NBL4 (erythrocyte protein band 4.1-like 4a/novel band 4.1-like 4), known to be involved in the Wnt (wingless-related mouse mammary tumour virus integration site) pathway. Some tumours from neutron-exposed mice appeared to have homozygous loss of some chromosomal markers., Conclusions: X-ray or fission neutron irradiation results in strongly enhanced tumour multiplicities. Comparison of tumour yields indicated a low Relative Biological Effectiveness of around 2-8 for fission neutrons compared with X-rays. LOH in intestinal tumours from neutron-exposed mice appeared to be more complex than previously reported for tumours from X-irradiated mice.

The co-grinding technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental stand point, as the technique does not require any toxic organic solvents. The present work is an attempt to use d-glucosamine HCl (G-HCl) as a potential excipient to improve dissolution rate of carbamazepine (CBZ) from physical mixtures and co-grinding formulations. The effect of order of grinding on dissolution of CBZ was also investigated. Co-ground of drug and G-HCL were prepared using different ratios using ball mill. The samples were subjected to different grinding times. In order to investigate the effect of grinding process on dissolution behaviour of CBZ, the drug was ground separately in the absence of glucosamine. Then the mixture of ground CBZ and un-ground d-glucosamine HCl were prepared. Physical mixtures of CBZ and G-HCl were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FT-IR, SEM, XRPD, and DSC. These results showed that the presence of glucosamine can increase dissolution rate of CBZ compared to pure CBZ. The results showed the order of grinding had a big impact on the dissolution performance of CBZ formulations containing glucosamine. All dissolution profiles generally showed that the fastest dissolution rate was obtained when ground CBZ was mixed with un-ground glucosamine. This was closely followed by the co-grinding of CBZ with glucosamine where lower grinding times showed the fastest dissolution. XRPD showed that the grinding of CBZ can reduce the percentage crystallinity of drug crystals. DSC study of ground CBZ showed that the grinding induced polymorphism transformations in the CBZ crystals and the limit and type of these transformations were related to the grinding time., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.