Search

Prolonging the lifespan of transplanted organs is critical to combat the shortage of this life‐saving resource. Chronic rejection, with irreversible demise of the allograft, is often caused by the development of donor‐specific HLA antibodies. Currently, enumerating molecular (amino acid) mismatches between recipient and donor is promoted to identify patients at higher risk of developing HLA antibodies, for use in organ allocation, and immunosuppression‐minimization strategies. We have counseled against the incorporation of such approaches into clinical use and hypothesized that not all molecular mismatches equally contribute to generation of donor‐specific immune responses. Herein, we document statistical shortcomings in previous study design: for example, use of individuals who lack the ability to generate donor‐specific‐antibodies (HLA identical) as part of the negative cohort. We provide experimental evidence, using CRISPR‐Cas9‐edited cells, to rebut the claim that the HLAMatchmaker eplets represent "functional epitopes." We further used unique sub‐cohorts of patients, those receiving an allograft with two HLA‐DQ mismatches yet developing antibodies only to one mismatch (2MM1DSA), to interrogate differential immunogenicity. Our results demonstrate that mismatches of DQα05‐heterodimers exhibit the highest immunogenicity. Additionally, we demonstrate that the DQα chain critically contributes to the overall qualities of DQ molecules. Lastly, our data proposes that an augmented risk to develop donor‐specific HLA‐DQ antibodies is dependent on qualitative (evolutionary and functional) divergence between recipient and donor, rather than the mere number of molecular mismatches. Overall, we propose an immunological mechanistic rationale to explain differential HLA‐DQ immunogenicity, with potential ramifications for other pathological processes such as autoimmunity and infections. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population‐based studies using conventional T2‐weighted brain magnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population‐based studies with brain MRI scans. We estimated and meta‐analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13–2.68) and 1.48 (95% CI, 1.12–1.96) fold, respectively. For stroke, meta‐analyses yielded HRs of 1.59 (95% CI, 1.04–2.42) for overall arteries and 2.11 (95% CI, 1.45–3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2‐weighted brain MRI‐based brain diameter assessment in estimating the risk of dementia and stroke. [ABSTRACT FROM AUTHOR]

Given the anatomical and functional similarities between the retina and the brain, the retina could be a "window" for viewing brain structures. We investigated the association between retinal nerve fiber layers (peripapillary retinal nerve fiber layer, ppRNFL; macular ganglion cell‐inner plexiform layer, GC‐IPL; and macular ganglion cell complex, GCC), and brain magnetic resonance imaging (MRI) parameters in young health adults. We included 857 students (mean age: 23.3 years, 71.3% women) from the i‐Share study. We used multivariate linear models to study the cross‐sectional association of each retinal nerve layer thickness assessed by spectral‐domain optical coherence tomography (SD‐OCT) with structural (volumes and cortical thickness), and microstructural brain markers, assessed on MRI globally and regionally. Microstructural MRI parameters included diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI). On global brain analysis, thicker ppRNFL, GC‐IPL and GCC were all significantly associated with patterns of diffusion metrics consistent with higher WM microstructural integrity. In regional analyses, after multiple testing corrections, our results suggested significant associations of some retinal nerve layers with brain regional gray matter occipital volumes and with diffusion MRI parameters in a region involved in the visual pathway and in regions containing associative tracts. No associations were found with global volumes or with global or regional cortical thicknesses. Results of this study suggest that some retinal nerve layers may reflect brain structures. Further studies are needed to confirm these results in young subjects. [ABSTRACT FROM AUTHOR]

This article interrogates the depiction of working‐class and subaltern characters in neoliberal US cinema. Deploying a Marxian class schema in a content analysis of 53 top‐grossing films released between 1980 and 2010, we find working‐class characters unexpectedly prominent. They appear in most films, lead in a plurality, and are far more often heroes than heavies. Yet the vast majority are white, male and US‐born while exhibiting near ubiquitous subordination to up‐class co‐leads, mainly professional‐managers. Most working‐class characters also die or exit their class by film's end, abdicating agency and leaving up‐class figures in charge. We argue this amounts to a metaframe of nostalgic resignation: a collective image mobilizing masculinity and Eurocentrism to justify a historic loss of working‐class power. In contrast to critical, disconnected or escapist models of mass media's relation to actual social inequality, we argue these findings support a reproductionist (Althusser 2014) or propagandist (Herman and Chomsky 2002) understanding of that dynamic enriched by Hall's "racially structured dominance" approach (1980). [ABSTRACT FROM AUTHOR]

Summary: High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9–10/10 HLA‐matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1, using the locus median to stratify patients with 'high' or 'low' HED. Patients with high HED‐B and ‐DRB1 showed significantly improved disease‐free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED‐B + ‐DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non‐relapse‐mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED‐B + ‐DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA‐DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is limited literature on the prevalence of incidental brain MRI findings in the Hispanic/Latino population, despite their increased prevalence of vascular disease and undertreatment of chronic conditions. The purpose of our study was to determine the prevalence of clinically relevant incidental findings on brain MRI examinations obtained as a part of the Study of Latinos–Investigation of NeuroCognitive Aging MRI (SOL‐INCA‐MRI) study. Methods: Brain MRI examinations were obtained on 1389 participants in the SOL‐INCA‐MRI study, a cross‐sectional ancillary study of the Hispanic Community Health Study, Study of Latinos, which is a longitudinal, community‐based study. Study design of SOL‐INCA‐MRI involves imaging cognitively normal and participants with mild cognitive impairment. Brain MRI findings were categorized as Level 1 (normal), Level 1.5 (findings of unclear medical significance), Level 2 (potential medical concern), or Level 3 (medically urgent). This article focuses on Level 2 and Level 3 findings. Results: The average age of the sample was 60.8 years (+/– 10.3 years), 66.1% were females. Level 2 and 3 findings were identified in 117 participants, (8.4%), of which 109 (7.8%) were recommended for medical follow‐up (Level 2), and 8 (0.6%) were recommended for immediate medical attention (Level 3). Brain MRI findings consisted of chronic infarction in 33 (2.4%), vascular abnormality in 27 (1.9%), intracranial mass in 20 (1.4%), other intracranial findings in 28 (2.0%), and skull base/extracranial findings in 26 (1.9%) patients. Conclusion: Incidental findings of clinical relevance were common among SOL‐INCA‐MRI participants, but rarely required urgent medical intervention. [ABSTRACT FROM AUTHOR]

The relationship between hippocampal subfield volumetry and verbal list‐learning test outcomes have mostly been studied in clinical and elderly populations, and remain controversial. For the first time, we characterized a relationship between verbal list‐learning test outcomes and hippocampal subfield volumetry on two large separate datasets of 447 and 1,442 healthy young and middle‐aged adults, and explored the processes that could explain this relationship. We observed a replicable positive linear correlation between verbal list‐learning test free recall scores and CA1 volume, specific to verbal list learning as demonstrated by the hippocampal subfield volumetry independence from verbal intelligence. Learning meaningless items was also positively correlated with CA1 volume, pointing to the role of the test design rather than word meaning. Accordingly, we found that association‐based mnemonics mediated the relationship between verbal list‐learning test outcomes and CA1 volume. This mediation suggests that integrating items into associative representations during verbal list‐learning tests explains CA1 volume variations: this new explanation is consistent with the associative functions of the human CA1. [ABSTRACT FROM AUTHOR]

The psychological mechanisms underlying infants' selective social learning are currently a subject of controversy. The main goal of the present study was to contribute data to this debate by investigating whether domain‐specific or domain‐general abilities guide infants' selectivity. Eighteen‐month‐olds observed a reliable and an unreliable speaker, and then completed a forced‐choice word learning paradigm, two theory of mind tasks, and an associative learning task. Results revealed that infants showed sensitivity to the verbal competence of the speaker. Additionally, infants with superior knowledge inference abilities were less likely to learn from the unreliable speaker. No link was observed between selective social learning and associative learning skills. These results replicate and extend previous findings demonstrating that socio‐cognitive abilities are linked to infants' selective social learning. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Oral health inequities and limited access to care cause patients to seek dental treatment in hospital emergency departments. In addition, conventional clinic models and curricular limitations may result in inadequate experiences for students learning urgent dental care. The aim of the current study was to investigate student perceptions of a novel dental school urgent care clinic model. Methods: A mixed‐methods, cross‐sectional study design was used to survey third‐year and fourth‐year students at a Midwest dental school in spring 2020 about their experiences providing patient care in the school's internal urgent care center. Along with a structured curriculum, the urgent care clinic model incorporates an on‐site partnership with a community health center and a hospital emergency department affiliation that serves as a referral base to provide students with their learning experiences. Results: Of 81 students, 78 completed the survey (96% response rate). The majority of students treated 50 or more patients. From their urgent care experiences, a majority of students felt prepared to manage patients with acute dental pain and swelling (72/77, 94%), and reported a better understanding of interprofessional collaborations in dentistry (42/77, 55%) and the importance of providing urgent dental care to underserved patients (72/77, 94%). Most students (64/75, 85%) were more likely to offer urgent dental care services to underserved populations in future practice. Conclusion: This collaborative school‐based urgent care clinic model incorporating community partnerships provided transformative learning experiences, positively impacted student perceptions of their learning, and influenced future practice behaviors related to urgent dental care. [ABSTRACT FROM AUTHOR]

Objectives: Administering anesthesia to the inferior alveolar nerve is 1 of the most stressful processes in dental training. Most studies using virtual reality (VR) for dental training have used non‐immersive technologies. The purpose of this work is to assess the impact of immersive technologies on skills training. Methods: On May 2019, an experimental study was conducted with 163 clinical dental students, divided into 4 groups across 2 phases (preceptorship and training) with haptic feedback either On or Off. The participants trained on the inferior alveolar dental anesthesia procedure in a haptic VR simulator. Their technical skills were evaluated in terms of needle insertion features which were computed from a haptic device providing kinematic data. Also, the participants reported their subjective experience with syringe handling and simulator sickness. A machine learning method was implemented to automatically evaluate the needle insertion point performance of the student. Results: Groups receiving immersive preceptorship and/or immersive training showed more accuracy and confidence in administering the anesthesia. Participants perceived a high sense of realism with the haptic feedback when handling the syringe. The machine learning method was validated, with an accuracy of 84%, as a good classifier to assess a student's needle insertion point performance. Conclusions: The immersive VR simulator allows the practice of the inferior alveolar nerve block under near real conditions and with immediate feedback to the dental student with respect to the needle insertion point. This machine learning based automatic evaluation provides a method to improve technical skills, contributing to dental training. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether brain artery diameters measured on conventional T2‐weighted brain MRI images relate to dementia and stroke outcomes across distinct populations. We aimed this study to evaluate the association of T2‐weighted brain artery luminal diameters with dementia and stroke in three distinct population‐based studies. Methods: Three longitudinal population‐based studies with 8420 adults >40 years old (Northern Manhattan Study [NOMAS] from the United States, and the Rotterdam Study [RS], from the Netherlands, and Three‐City, from France) with brain MRI scans obtained between 1999 and 2015. The median follow‐up time for clinical events ranged between 7 and 12.5 years. We tested our hypothesis in each cohort separately due to local data‐sharing regulations. The exposure variable was brain carotid and basilar artery luminal diameters measured on MRI axial T2‐weighted scans. Multivariable hazard ratios (HRs) and their 95% confidence intervals (CI) expressed the risk of dementia and stroke (primary outcomes) associated with the lowest (<5th) and highest (>95th) percentiles of the rank‐normalized brain artery diameters compared to a reference group defined as the diameters distributed between the 5th and 95th percentiles. Secondary outcomes included total and vascular mortality, and fatal and nonfatal cardiovascular and coronary end points. Results: Among the three cohorts (mean age ranged from 65 to 73 y, ≥57% women), 335 participants developed dementia and 331 strokes. Compared with the reference group, participants with arterial diameters >95th percentile had a higher risk of dementia (HR range 1.15‐4.50) and any stroke (HR range 1.29‐2.03). For secondary outcomes, participants with arterial diameters >95th percentile had a consistent higher risk of coronary outcomes, vascular mortality and a composite of any vascular events. The results were less supportive of a higher risk of events among participants with arterial diameters <5th percentile except for vascular mortality. Conclusions: Individuals with dilated brain arteries are at higher risk of dementia and vascular events. Our findings were consistency across distinct populations in spite of using a non‐enhanced, conventional T2‐weighted MRI sequence. Understanding the underlying physiopathology of the reported associations, particularly with dementia and stroke, might reveal novel vascular contributions to dementia [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Competence in nitrous oxide/oxygen (N2O/O2) inhalation sedation is expected of dental graduates, but applying what is learned through didactic instruction to patient care can be challenging without firsthand experience. Therefore, the purpose of the current study was to evaluate the impact of experiential learning on dental students' confidence and sense of preparedness for administration of N2O/O2. Methods: A biphasic, mixed methods study was conducted at a Midwestern dental school and included 2 cohorts of dental students. In Phase 1 (spring 2019), a cross‐sectional study design was used to survey outgoing third‐year and fourth‐year students who received didactic N2O/O2 instruction alone. In Phase 2 (summer 2019), a nonrandomized, preintervention‐postintervention study design was used to survey incoming third‐year students before and after a hands‐on N2O/O2 laboratory exercise. Results: Of the 79 Phase 1 students (99% response rate), all believed a firsthand learning experience with N2O/O2 during didactic learning would increase their confidence and preparedness when administering to a patient (both P <.001). Of the 41 Phase 2 students (100% response rate), after the lab exercise, all felt that firsthand experience enhanced classroom instruction and increased confidence and preparedness when administering N2O to a patient (all P <.001). Fifty‐six (71%) Phase 1 and 39 (80%) Phase 2 students believed classroom instruction alone was inadequate to prepare them to administer N2O/O2 (both P <.001). Conclusions: Our results strongly suggest that experiential learning of N2O/O2 inhalation sedation through a hands‐on laboratory exercise should be incorporated into the predoctoral curricula of dental schools. [ABSTRACT FROM AUTHOR]

Spatial atomic layer deposition (SALD) is a recent approach 100 times faster than conventional atomic layer deposition (ALD), even at atmospheric pressure. Previous works exploited these assets focussing on high‐rate, large‐area deposition for scaling‐up into mass production. Conversely, this work shows that SALD indeed represents an ideal platform for area‐selective deposition of functional materials by proper design and miniaturization of close‐proximity SALD heads. In particular, the potential offered by 3D printing is used to fabricate low‐cost customized close‐proximity heads, which can be easily designed and modified to obtain different deposition areas, free‐form patterns, and even complex multimaterial structures. Finally, by designing a miniaturized head with circular concentric gas channels, 3D printing of functional materials can be performed with nanometric resolution in Z. This constitutes a new gas‐phase 3D printing approach. Because the process is based on ALD reactions, conformal and continuous thin films of functional materials can be printed at low temperatures and with high deposition rate in the open air. This approach represents a new versatile way of printing functional materials and devices with spatial and topological control, thus extending the potential of SALD and ALD in general, and opening a new avenue in the field of area‐selective deposition of functional materials. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to understand the experiences junior faculty have during their professional socialisation as educators and how they perceive the need and value of mentorship. Methods: A cross‐sectional qualitative study design was used. Data were collected in 2019 through a pre‐survey and focus groups with junior faculty (defined as 0‐5 years) across four institutions in Australia and the United States of America. Framework analysis was used to identify themes in the data, based on our defined research questions, and socio‐cognitive career theory was applied to guide our analysis. Results: A total of 22 junior faculty participated in the study. Only one of the four institutions had a formal mentoring programme for junior dental faculty. At this institution, 83% of participants indicated they were likely/extremely likely to remain in dental education. Across the three institutions where formal mentoring for junior dental faculty was not available, only 40% of participants indicated they were likely/extremely likely to remain in dental education. We identified five themes in the qualitative data: motivation for career choice, the importance of relationships, personal goals and the need for self‐direction, expectations of the role, and institutional effects. Conclusion: Our findings suggest that mentoring is a critical factor in a junior faculty member's experience entering and socialising into a career in dental education. The perceived value of mentoring emerged across all themes, both from the perspective of participants who had received formal mentoring and those who had not. [ABSTRACT FROM AUTHOR]

Background: Environmental factors, such as nutrition, influence brain physiology and health throughout the life course. While research has focused on the extremes of the age spectrum, less is known about early adulthood, yet a critical period for the consolidation of brain maturation and the building of adult behaviors. Nutrition may impact late maturational changes in the post‐adolescent brain and contribute to the degree of brain reserve that minimizes the risk to develop dementia. We took advantage of a large sample of young adults to evaluate the association of dietary behavior with brain structure characteristics. Method: This cross‐sectional study included 1721 university students (18‐35 years‐old) from the French i‐Share cohort, who underwent brain MRI. A 12‐item online Food Frequency Questionnaire was used to evaluate consumption in major food groups and to determine dietary patterns from Principal Component Analysis (PCA). Multivariable‐adjusted linear regressions were used to estimate the association of PCA scores with brain structure (cortical thickness and surface area, grey matter and white matter volumes, diffusion parameters). Result: The first PCA component (explained variance, 17%) contrasted a healthy diet (higher fruit and vegetable intakes) to a poor diet (higher fast food, sugary drink and snack consumptions). In models adjusted for total intracranial volume, age, sex, physical activity, body mass index, alcohol and tobacco consumptions, a higher PCA score (reflecting healthier diet) was associated with lower total gray matter volume (β for 1 point score = –0.17 [95%CI, –0.31; –0.03] cm3), in various brain areas (Figure). Healthy diet was also associated with lower global white matter volume (β = –0.18 [–0.32; –0.03] cm3). No association was found with diffusion tensor imaging, and neurite orientation dispersion and density imaging metrics in the white matter. Conclusion: In this large sample of young adults, healthier diet was associated with lower brain volumes, independent of multiple potential confounders. Gray matter volume loss during post‐adolescence is a marker of brain maturation; thus, environmental factors emphasizing this loss may benefit maturation. Our results raise the hypothesis that a healthy diet may favor and a poor diet may hamper brain maturation; an assumption which deserves further investigation in other populations. [ABSTRACT FROM AUTHOR]

We detected a somatic mutation in the HLA‐B gene in a Czech hematooncological patient. We followed the development of this somatic mutation during the transition from severe aplastic anaemia through to myelodysplastic syndrome to acute myeloid leukaemia until haploidentical related transplantation. The somatic mutation differs from HLA‐B*14:02 in exon 3 resulting in an exchange from cysteine to serine at position 101 of the mature protein. Homology modelling of mutated S101 in HLA‐B*14 indicated possible conformational changes, which might also result in an aberrant expression. The assumption is that somatic mutation arose as a possible result of a selection mediated by a protective immune response against leukaemia. [ABSTRACT FROM AUTHOR]

Infants can detect individuals who demonstrate emotions that are incongruent with an event and are less likely to trust them. However, the nature of the mechanisms underlying this selectivity is currently subject to controversy. The objective of this study was to examine whether infants' socio‐cognitive and associative learning skills are linked to their selective trust. A total of 102 14‐month‐olds were exposed to a person who demonstrated congruent or incongruent emotional referencing (e.g., happy when looking inside an empty box), and were tested on their willingness to follow the emoter's gaze. Knowledge inference and associative learning tasks were also administered. It was hypothesized that infants would be less likely to trust the incongruent emoter and that this selectivity would be related to their associative learning skills, and not their socio‐cognitive skills. The results revealed that infants were not only able to detect the incongruent emoter, but were subsequently less likely to follow her gaze toward an object invisible to them. More importantly, infants who demonstrated superior performance on the knowledge inference task, but not the associative learning task, were better able to detect the person's emotional incongruency. These findings provide additional support for the rich interpretation of infants' selective trust. [ABSTRACT FROM AUTHOR]

Abstract: Although there is mounting evidence that selective social learning begins in infancy, the psychological mechanisms underlying this ability are currently a controversial issue. The purpose of this study is to investigate whether theory of mind abilities and statistical learning skills are related to infants’ selective social learning. Seventy‐seven 18‐month‐olds were first exposed to a reliable or an unreliable speaker and then completed a word learning task, two theory of mind tasks, and a statistical learning task. If domain‐general abilities are linked to selective social learning, then infants who demonstrate superior performance on the statistical learning task should perform better on the selective learning task, that is, should be less likely to learn words from an unreliable speaker. Alternatively, if domain‐specific abilities are involved, then superior performance on theory of mind tasks should be related to selective learning performance. Findings revealed that, as expected, infants were more likely to learn a novel word from a reliable speaker. Importantly, infants who passed a theory of mind task assessing knowledge attribution were significantly less likely to learn a novel word from an unreliable speaker compared to infants who failed this task. No such effect was observed for the other tasks. These results suggest that infants who possess superior social‐cognitive abilities are more apt to reject an unreliable speaker as informant. A video abstract of this article can be viewed at: https://youtu.be/zuuCniHYzqo [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (cSVD) is a leading cause of vascular cognitive impairment and dementia. Mounting evidence suggests that early life factors contribute to cSVD. Genetic risk loci for white matter hyperintensities (WMH), the most common MRI‐marker of cSVD in older age, were recently found to show strong associations with white matter microstructure on diffusion tensor imaging (DTI) already in young adults in their twenties. Here we aimed to use multi‐shell diffusion imaging to further explore genetic determinants of white matter microstructure across the adult lifespan and its relation with cSVD. Method: In 1,758 participants (mean age: 22.1 [18 to 35] years) from the i‐Share student cohort who underwent multi‐shell diffusion imaging, we used neurite orientation dispersion and density imaging (NODDI) to generate tissue‐based markers of white matter microstructure including neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) in 28 brain regions. We ran genome‐wide association studies (GWAS) of all 84 NODDI markers in i‐Share and looked up genome‐wide significant variants in UK Biobank (N = 33,224, mean age: 64.3 [45 to 82] years) to identify loci with a lifecourse effect on these phenotypes. Next, we studied the association of genetically determined WMH volume and blood pressure with NODDI phenotypes in i‐Share using Mendelian randomization (MR). Result: This first GWAS of 84 NODDI phenotypes in young adults identified 21 genome‐wide significant loci. Three of them, associated mostly with NDI, also showed significant association with NODDI phenotypes in middle‐aged to older UK Biobank participants, including a known WMH locus near VCAN, a cerebrovascular matrisome gene. Using MR we found that genetically determined WMH, previously shown to predict Alzheimer‐type dementia, was associated with lower NDI in young adults. In contrast, genetically determined blood pressure, although an important risk factor for WMH volume, did not show any significant association with NODDI phenotypes in young adults. Conclusion: Our results suggest that NODDI markers, especially NDI, have a substantial genetic component already in early adulthood and may inform early mechanisms underlying the vascular contribution to dementia. Replication of these findings in additional CHARGE cohorts (Rhineland study, Framingham Heart study) is underway. [ABSTRACT FROM AUTHOR]

ABSTRACT 3,3-Disubstituted oxetane monomers were found to undergo rapid, exothermic redox initiated cationic ring-opening polymerization in the presence of a diaryliodonium or triarylsulfonium salt oxidizing agent and a hydrosilane reducing agent. The redox reaction requires a noble metal complex as a catalyst and several potential catalysts were evaluated. The palladium complex, Cl2(COD)PdII, was observed to provide good shelf life stability while, at the same time, affording high reactivity in the presence of a variety of hydrosilane reducing agents. A range of structurally diverse oxetane monomers undergo polymerization under redox cationic conditions. When a small amount of an alkylated epoxide was added as a 'kick-start' accelerator to these same oxetanes, the redox initiated cationic polymerizations were extraordinarily rapid owing to the marked reduction in the induction period. A mechanistic interpretation of these results is offered. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1854-1861 [ABSTRACT FROM AUTHOR]

Hemispheric lateralization for spatial attention and its relationships with manual preference strength and eye preference were studied in a sample of 293 healthy individuals balanced for manual preference. Functional magnetic resonance imaging was used to map this large sample while performing visually guided saccadic eye movements. This activated a bilateral distributed cortico-subcortical network in which dorsal and ventral attentional/saccadic pathways elicited rightward asymmetrical activation depending on manual preference strength and sighting eye. While the ventral pathway showed a strong rightward asymmetry irrespective of both manual preference strength and eye preference, the dorsal frontoparietal network showed a robust rightward asymmetry in strongly left-handers, even more pronounced in left-handed subjects with a right sighting-eye. Our findings brings support to the hypothesis that the origin of the rightward hemispheric dominance for spatial attention may have a manipulo-spatial origin neither perceptual nor motor per se but rather reflecting a mechanism by which a spatial context is mapped onto the perceptual and motor activities, including the exploration of the spatial environment with eyes and hands. Within this context, strongly left-handers with a right sighting-eye may benefit from the advantage of having the same right hemispheric control of their dominant hand and visuospatial attention processing. We suggest that this phenomenon explains why left-handed right sighting-eye athletes can outperform their competitors in sporting duels and that the prehistoric and historical constancy of the left-handers ratio over the general population may relate in part on the hemispheric specialization of spatial attention. Hum Brain Mapp 36:1151-1164, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Simultaneous free radical and cationic photopolymerizations of mixtures of multifunctional acrylate and oxetane monomers were carried out to provide hybrid interpenetrating network polymers. The use of 'kick-started' oxetanes in which oxetane monomers are accelerated by the use of small amounts of certain highly substituted epoxides provides dual independent radical and cationic systems with similar rates of photopolymerization leading to homogeneous interpenetrating networks. The combined photopolymerizations are very rapid and afford crosslinked network films that are colorless, hard, and transparent. The networks display no indications of phase separation. The use of this technology in various applications such as coatings, 3D imaging, and for composites is discussed. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 594-601 [ABSTRACT FROM AUTHOR]

ABSTRACT The ability of certain alkyl substituted epoxides to accelerate the photoinitiated cationic ring-opening polymerizations of oxetane monomers by substantially reducing or eliminating the induction period altogether has been termed by us 'kick-starting.' In this communication, the rates of photopolymerization of several model 'kick-started' oxetane systems were quantified and compared with the analogous biscycloaliphatic epoxide monomer, 3,4-epoxycyclohexylmethyl 3′,4′-epoxycyclohexanecarboxylate (ERL). It has been found that the 'kick-started' systems undergo photopolymerization at rates that are at least two-fold faster than ERL. These results suggest that 'kick-started' oxetanes could replace ERL in many applications in which high speed ultraviolet induced crosslinking photopolymerizations are carried out. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 586-593 [ABSTRACT FROM AUTHOR]

ABSTRACT In the presence of small amounts of 2,2-dialkyl-, 2,2,3-trialkyl-, or 2,2,3,3-tetraalkyl substituted epoxides such as isobutylene oxide, 1,2-limonene oxide, and 2,2,3,3,-tetramethyl oxirane, the photoinitiated cationic ring-opening polymerizations of 3,3-disubstituted oxetanes are dramatically accelerated. The acceleration affect was attributed to an increase in the rate of the initiation step of these latter monomers. Both mono- and disubstituted oxetane monomers are similarly accelerated by the above-mentioned epoxides to give crosslinked network polymers. The potential for the use of such 'kick-started' systems in applications such as coatings, adhesives, printing inks, dental composites and in three-dimensional imaging is discussed. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2934-2946 [ABSTRACT FROM AUTHOR]

Drawing on data from Peru, this article explores how poverty mediates diverse risks in rural children's lives. It offers four main arguments. First, risk is not simply a feature of 'extraordinary' childhoods, but integral to everyday, 'ordinary' lives. Second, children's responses to adversity are crucially shaped by sociomoral considerations. Third, children participate actively in household risk mitigation, their engagement structured by individual (biographical) and collective factors. Fourth, changing circumstances present new opportunities and challenges for children living with adversity. Current approaches focusing on so-called 'objective' risks neglect children's own priorities and subjective experiences. [ABSTRACT FROM AUTHOR]

This paper reviews the field of cationic UV-curing and reports recent progress made in understanding the fundamental chemistry and in technology applications. Radiation curing technologies are expanding rapidly on an industrial scale and interest in cationic photopolymerizations has advanced rapidly. In particular, the cationic UV-curing process presents additional benefits, including: the absence of air inhibition, a 'dark-curing' reaction, low levels of toxicity and irritation, and a lower volume shrinkage during photopolymerization. In this review, a large number of papers and patents are reviewed and critically discussed specifically with respect to the application of cationic UV-curing technology in the field of coatings, composites, adhesives, and inks. [ABSTRACT FROM AUTHOR]

The cyclic azodioxide, 1,4,4-trimethyl-2,3-diazabicyclo[3.2.2]non-2-ene 2,3-dioxide ( 5), displays the unique ability to function as a thermally reversible inhibitor for the UV-induced photoinitiated cationic polymerizations of epoxide and vinyl ether monomers. At room temperature and below, the photopolymerizations are suppressed due to the capture of photogenerated initiating protons by the cis-azodioxide group, which is both basic and serves as a bidentate coordinating group. However, at higher temperatures, the azodioxide group reverts to its ring-opened dinitroso isomer and, as a consequence, loses its ability to coordinate to protons. Protons released during this process subsequently initiate the cationic polymerizations of the monomers. Reversible inhibitors such as 5 have several potential applications such as in the design of one-component photoactivatable structural and assembly adhesives and in composites. [ABSTRACT FROM AUTHOR]

Diaryliodonium salts spontaneously form crystalline 1:1 supramolecular complexes at room temperature in good to excellent yields with 18-crown-6 ether and its cyclohexano- and benzo-substituted analogs. The complexes were characterized using IR, UV, MS, 1H, and 13C-NMR spectroscopy and by single crystal X-ray crystallography. The analytical data obtained were consistent with a structure in which the positively charged iodine atom of diaryliodonium cation is positioned above and over the center of the crown ether ring with the positively charged iodine atom coordinated to the crown ether oxygen atoms. The diaryliodonium salt-crown ether complexes are photosensitive and were used to carry out the photoinitiated cationic polymerizations of a number of mono- and difunctional monomers. During irradiation with UV light, the supramolecular complexes undergo photolysis with the generation of a Brønsted acid and with the concomitant release of the crown ether. When used as photoinitiators, the crown ether that is released markedly influences the kinetics of the subsequent cationic polymerization of the monomer. Further studies demonstrated that the photolysis of diaryliodonium salt-crown ether supramolecular complexes can be photosensitized using typical-electron transfer photosensitizers. Free radical-promoted photosensitization using typical unimolecular free radical photoinitiators such as 2,2-dimethoxy-2-phenylacetophenone also takes place readily. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013 [ABSTRACT FROM AUTHOR]

Polyisobutylene-based UV cured networks potentially useful as sealants were synthesized by photopolymerization of well-defined polyisobutylene methacrylate (PIB-MA), acrylate (PIB-A) and vinyl ether (PIB-VE) di- and trifunctional macromonomers. The kinetics of photocrosslinking were measured using an optical pyrometer apparatus and optimized with respect to different experimental parameters. PIB-MA/A macromonomers displayed enhanced reactivity in radical photopolymerization in the presence of a bis(acylphosphine) oxide photoinitator. PIB-VE macromonomers exhibited a high rates of photopolymerization with (4- n-octyloxyphenyl)phenyliodonium hexafluroantimonate as the photoinitiator. The rates as well as the ultimate monomer conversions were increased by increasing the irradiation light intensity. The inherent induction period associated with oxygen inhibition in the photopolymerization of PIB-MA was significantly reduced by optimizing the choice of photoinitiator. A detailed investigation of the concentration of MA/A/VE end groups revealed the presence of a prominent saturation effect in the photopolymerization of PIB-A, which was absent with PIB-MA and PIB-VE. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013 [ABSTRACT FROM AUTHOR]

Two novel redox initiator systems have been developed for carrying out the cationic polymerizations of vinyl and heterocyclic monomers. The initiators are based on various onium salts as the oxidant together with an alkylborane or an organosilane as the reducing agent. Using both redox cationic initiator systems, the polymerizations of a wide variety of monomers can be carried out at or below room temperature in the presence or absence of unreactive solvents. Also described in this communication is the novel use of a two-component redox system in which the reducing agent, a silane, is delivered to the monomer sample in the vapor state. Optical pyrometry (infrared thermography) was employed as a convenient method with which to monitor the polymerizations in real-time. A study of the effects of variations in the structures of the onium salt, the silane and the type of noble metal catalyst were carried out. The use of these initiator systems for carrying out commercially attractive crosslinking polymerizations for coatings, composites and electronic encapsulations is discussed. [ABSTRACT FROM AUTHOR]

Limonene 1,2-oxide (LMO) and α-pinene oxide (α-PO) are two high reactivity biorenewable monomers that undergo facile photoinitiated cationic ring-opening polymerizations using both diaryliodonium salt and triarylsufonium salt photoinitiators. Comparative studies showed that α-PO is more reactive than LMO, and this is because it undergoes a simultaneous double ring-opening reaction involving both the epoxide group and the cyclobutane ring. It was also observed that α-PO also undergoes more undesirable side reactions than LMO. The greatest utility of these two monomers is projected to be as reactive diluents in crosslinking photocopolymerizations with multifunctional epoxide and oxetane monomers. Prototype copolymerization studies with several difunctional monomers showed that LMO and α-PO were effective in increasing the reaction rates and shortening the induction periods of photopolymerizations of these monomers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013 [ABSTRACT FROM AUTHOR]

Several epoxy difunctional hybrid alkylene-silicone telomers with different silicone characters and organic spacers (linkers) were prepared via the platinum-catalyzed polyhydrosilylation of α,ω-dihydrosiloxanes and α,ω-dienes. Thereafter, the resulting SiH-terminated prepolymers were terminally functionalized with 4-vinyl-1,2-epoxycyclohexane or allyl glycidyl ether. In the presence of a lipophilic cationic photoinitiator, the terminally epoxy-functionalized hybrid alkylene-silicone telomers were photopolymerized to give crosslinked, soft, elastomeric, and transparent films. The progress of the photoinitiated cationic ring-opening epoxide polymerizations was monitored using optical pyrometry. Potential applications for these novel photocurable epoxy-functional telomers are as modifiers for UV curable coatings, printing inks, adhesives, and release coatings. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Redox systems composed of a diaryliodonium or a triarylsulfonium salt together with a silane bearing SiH groups were used for the in situ generation of strong Brønsted acids at room temperature in the presence of alkyl glycidyl ether monomers. Secondary oxiranium intermediates are generated with lifetimes from minutes to hours at room temperature. These systems undergo rapid, exothermic cationic chain polymerization when the temperature is raised. Metastable monomer-redox initiator systems were also observed to undergo frontal polymerizations when a localized heat source is applied to the sample. The application of these delayed cationic ring-opening polymerization systems for the development of one-component structural adhesives that undergo rapid thermosetting at low temperatures are discussed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011 [ABSTRACT FROM AUTHOR]

Aim: The goal of this investigation was to determine whether epigenetic modifications in the IFNG promoter are associated with an increase of IFNG transcription in different stages of periodontal diseases. Materials and Methods: DNA was extracted from gingival biopsy samples collected from 47 total sites from 47 different subjects: 23 periodontally healthy sites, 12 experimentally induced gingivitis sites and 12 chronic periodontitis sites. Levels of DNA methylation within the IFNG promoter containing six CpG dinucleotides were determined using pyrosequencing technology. Interferon gamma mRNA expression was analysed by quantitative polymerase chain reactions using isolated RNA from part of the biological samples mentioned above. Results: The methylation level of all six analysed CpG sites within the IFNG promoter region in the periodontitis biopsies {52% [interquartile range, IQR (43.8%, 63%)]} was significantly lower than periodontally healthy samples {62% [IQR (51.3%, 74%)], p=0.007} and gingivitis biopsies {63% [IQR (55%, 74%)], p=0.02}. The transcriptional level of IFNG in periodontitis biopsies was 1.96-fold and significantly higher than tissues with periodontal health (p=0.04). Although the mRNA level from experimental gingivitis samples exhibited an 8.5-fold increase as compared with periodontally healthy samples, no significant methylation difference was observed in experimental gingivitis sample. Conclusions: A hypomethylation profile within IFNG promoter region is related to an increase of IFNG transcription present in the chronic periodontitis biopsies, while such an increase of IFNG in experimentally induced gingivitis seems independent of promoter methylation alteration. [ABSTRACT FROM AUTHOR]

Aim: The goal of this investigation was to determine whether epigenetic modifications in the IFNG promoter are associated with an increase of IFNG transcription in different stages of periodontal diseases. Materials and Methods: DNA was extracted from gingival biopsy samples collected from 47 total sites from 47 different subjects: 23 periodontally healthy sites, 12 experimentally induced gingivitis sites and 12 chronic periodontitis sites. Levels of DNA methylation within the IFNG promoter containing six CpG dinucleotides were determined using pyrosequencing technology. Interferon gamma mRNA expression was analysed by quantitative polymerase chain reactions using isolated RNA from part of the biological samples mentioned above. Results: The methylation level of all six analysed CpG sites within the IFNG promoter region in the periodontitis biopsies {52% [interquartile range, IQR (43.8%, 63%)]} was significantly lower than periodontally healthy samples {62% [IQR (51.3%, 74%)], p=0.007} and gingivitis biopsies {63% [IQR (55%, 74%)], p=0.02}. The transcriptional level of IFNG in periodontitis biopsies was 1.96-fold and significantly higher than tissues with periodontal health (p=0.04). Although the mRNA level from experimental gingivitis samples exhibited an 8.5-fold increase as compared with periodontally healthy samples, no significant methylation difference was observed in experimental gingivitis sample. Conclusions: A hypomethylation profile within IFNG promoter region is related to an increase of IFNG transcription present in the chronic periodontitis biopsies, while such an increase of IFNG in experimentally induced gingivitis seems independent of promoter methylation alteration. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including the study of children growing up in poverty in Ethiopia; the research on the corrosive effect of rising inequalities in children's identities; and the feature on how children have become social and economic actors despite the constraints in their marginality.

Objectives To investigate the cross-sectional and longitudinal associations between performance-based measures of motor function and volume of white matter lesions (WMLs), and to examine the influence of the localization of these lesions. Methods At baseline, motor performances (maximum walking speed, Tinetti gait and balance subscales) were assessed in 1,702 subjects aged 80 years or younger from the Dijon (France), France center of the Three-City study. Volumes of WMLs lesions (total, periventricular, deep) were measured using an automated method of tissue segmentation and quantification of lesion size. At 8-year follow-up, walking speed was evaluated in 1,086 subjects. Results At baseline, mean and 95% confidence interval (CI) walking speed was lower in subjects with total volumes of WMLs ≥90th percentile (1.50 [1.45-1.55] m/s) than in subjects with lower volumes (1.56 [1.55-1.58] m/s; p = 0.004). Baseline total volumes of WMLs above the 90th percentile predicted walking speed decline during follow-up (odds ratio [95% CI] for having the greatest walking speed decline = 2.3 [1.3-4.1], p = 0.006). Moreover, high volumes of periventricular but not deep WMLs were associated with slower walking speed at baseline ( p = 0.005) and over time ( p = 0.001), and with lower Tinetti gait subscore ( p = 0.02). Interpretation Our study shows a cross-sectional and longitudinal association between high total volumes of WMLs, in particular volumes above the 90th percentile, and impaired mobility. These associations were independent of several confounders, including cognition, and were mainly accounted for by volumes of periventricular WMLs. These findings support the hypothesis of a vascular contribution to motor decline in the elderly. Ann Neurol 2009;65:706-715 [ABSTRACT FROM AUTHOR]

A novel catalytic method for carrying out the cationic polymerizations has been developed based on a redox initiator system in which the reducing component is delivered to the reaction mixture in the vapor state. The redox couple consists of a diaryliodonium salt that is dissolved in the monomer and a noble metal catalyst is added. The silane reducing agent is introduced to the reaction mixture in the vapor state using air as the carrier gas. Reduction of the diaryliodonium salt by the silane results in the liberation of a Brønsted superacid that initiates cationic polymerizations. A study of the effects of variations in the structures of the diaryliodonium salt, the silane, and the type of noble metal catalyst was carried out. In principle, the initiator system is applicable to all types of cationically polymerizable monomers and oligomers including: the ring‐opening polymerizations of such heterocyclic monomers as epoxides and oxetanes and, in addition, the polymerization of vinyl ether monomers such as vinyl ethers. The use of this initiator system for carrying out commercially attractive cross‐linking polymerizations for coatings, composites, and encapsulations is discussed. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1825–1835, 2009 [ABSTRACT FROM AUTHOR]

The irradiation of hybrid photopolymer systems consisting of a free radically polymerizable multifunctional acrylate monomer and a cationically polymerizable epoxide or oxetane monomer was conducted under conditions where only the free radical polymerization takes place. This results in the formation of a free‐standing polyacrylate network film containing quiescent oxonium ions along with the unreacted cyclic ether monomer. The subsequent application of a point source of heat to the film ignites a cationic ring‐opening frontal polymerization that emanates from that site and propagates to all portions of the irradiated sample. This article examines the impact of various molecular structural and experimental parameters on these novel hybrid frontal polymerizations that produce interpenetrating network polymers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4331–4340, 2007 [ABSTRACT FROM AUTHOR]

Multifunctional alkyl glycidyl ether and oxetane monomers are usually deemed to be poorly reactive and are consequently of limited use for high speed photocuring applications. However, these monomers can be made to undergo exceedingly rapid exothermic photopolymerization when combined with a multifunctional acrylate monomer and a corresponding free radical photoinitiator. Under optimum UV irradiation conditions, these hybrid photopolymerizations take place rapidly and substantially without an induction period. A mechanism was proposed on the basis of thermal acceleration of the cationic ring‐opening polymerizations induced by the fast exothermic free radical acrylate photopolymerization. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3759–3769, 2007 [ABSTRACT FROM AUTHOR]

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori–associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease–associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-β1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, developing colorectal cancer similar to human inflammatory bowel disease–associated neoplasia. TGF-β1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF-β1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression. We assessed association of functional polymorphisms (–1082G/A; –592C/A) and TGF-β1 (–509C/T; +869C/T) influencing the IL-10 production to colorectal cancer risk in a case–control study of 62 patients and 124 matched controls. No significant differences were observed among cancer patients and controls for IL-10 –1082G/A; –592C/A genotype frequencies. Evaluation of odds ratios (OR) for the TGF-β1 +869C/T genotypes showed a significant increased risk for individuals bearing +869CC genotype compared to +869CT- and +869TT-positive individuals. These results suggest that the +869C allele, responsible for a Leu→Pro substitution in the signal peptide sequence of the TGF-β1 protein, may have a predisposing role in the development of colorectal cancer. [ABSTRACT FROM AUTHOR]

Human breast cancer (BC) is characterized by a considerable clinical heterogeneity. Steroid hormone receptor expression and growth factor receptor expression have been considered suitable diagnostic and prognostic markers, whereas mutations of oncosuppressor and gatekeeper genes have been found associated with an increased risk for this malignancy. To evaluate the role that polymorphisms of genes involved in the regulation of inflammatory response might play in BC susceptibility, we investigated associations between cytokine functionally relevant polymorphisms in 84 BC patients compared to 110 age- and sex-matched controls. TNF-α (-308G/A), TGF-β1 (+869C/T), IL-10 (−1117G/A; −854C/T; −627C/A), and IFN-γ (874T/A) single nucleotide polymorphisms (SNPs) were identified by sequence-specific primers (SSP)-PCR or restriction fragment length polymorphism (RFLP)-PCR. Genotype or haplotype distributions for each polymorphisms were consistent with the HWE in these populations. We were unable to demonstrate differences in genotype or allele frequencies between patient and control groups. Data obtained in this study indicate that none of the cytokine SNPs studied is likely to have predisposing or protective effects on BC susceptibility. On the other hand, both positive and negative association with BC have been reported for some of the studied genotypes by different research groups. In conclusion, further studies involving larger numbers of subjects are required. [ABSTRACT FROM AUTHOR]

Myocardial infarction (AMI) is a complex multifactorial disorder. Platelet adhesion and thrombosis are pivotal events in the development of atherosclerotic lesions. Occlusive thrombus is almost exclusively initiated by plaque rupture and adhesion of platelets to subendothelial von Willebrand factor (vWf) by its specific platelet receptor, the α-chain of glycoprotein (GP) Ib-IX-V complex of the human platelet-specific antigens (HPA). Two polymorphisms have been reported in the sequence of GPIb-α. The first, a C/T transition at nucleotide 1018 results in an amino acid dimorphism (Thr/Met) at residue 145 of GPIb-α, which is located within the vWF-binding domain of the receptor. The second is a T/C polymorphism in the Kozak sequence at position −5 from the initiator ATG. This affects the receptor density on the platelet surface. We assessed 1018 C/T and −5 T/C Kozak polymorphisms to see whether they are associated with AMI in homogeneous populations of Sicilian patients with AMI. To this end, we have analyzed the distribution of 1018 C/T and −5 T/C Kozak polymorphisms in 105 young Sicilian patients (<46 years) and 110 healthy age-related controls, by PCR–SSP and PCR–RFLP. Our results demonstrate no significant differences in the frequency of 1018 C/T and −5 T/C Kozak polymorphism between patients with AMI and controls. Stratifying by gender, there is no difference between male and female patients and control data. Thus, our results indicate that the HPA-2 polymorphisms are not associated with an increased risk for AMI at early onset (< 46 years) both in men and in women. [ABSTRACT FROM AUTHOR]