Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOe4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOe2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond e2 and e4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

A Bayesian framework for age modeling of radiocarbon-dated peat deposits: Case studies from the Netherlands

Recently, Bayesian statistical software has been developed for age-depth modeling (wiggle-match dating) of sequences of densely spaced radiocarbon dates from peat cores. The method is described in non-statistical terms, and is compared with an alternative method of chronological ordering of 14C dates. Case studies include the dating of the start of agriculture in the northeastern part of the Netherlands, and of a possible Hekla-3 tephra layer in the same country. We discuss future enhancements in Bayesian age modeling.

The Golden Age? What the 100 Most Cited Articles in Terrorism Studies Tell Us

ln a context where widespread failings in the nature of terrorism research are well recognised - yet where the quantity of work is still enormous - is it possible to fairly assess whether the field is progressing or if it has become mired in mediocre research? Citation analysis is widely used to reveal the evolution and extent of progress in fields of study and to provide valuable insight into major trends and achievements. This study identifies and analyses the current 100 most cited journal articles in terrorism studies. A search was performed using Google Scholar for peer reviewed journal articles on subjects related to terrorism and counter-terrorism. The most cited papers were published across 62 journals which reflected the interdisciplinary nature of terrorism studies. Compared to other articles, the most cited papers were more likely to be the result of colloborative research and were also more likely to provide new data. 63 of the top 1-00 articles have been published since 2001. The findings are discussed in relation to the evolution of terrorism research and current debates on progress in the field.

Non-invasive Studies on Age Related Parameters Using a Blood Volume Pulse Sensor

A non-invasive technique is implemented to measure a parameter which is closely related to the distensibility of large arteries, using the second derivative of the infrared photoplethysmographic waveform. Thirty subjects within the age group of 20-61 years were involved in this pilot study. Two new parameters, namely the area of the photoplethysmographic waveform under the systolic peak, and the ratio of the time delay between the systolic and the diastolic peaks and the time period of the waveform ( T/T) were studied as a function of age. It was found that while the parameter which is supposed to be a marker of distensibility of large arteries and T /T values correlate negatively with age, the area under the systolic peak correlates positively with age. The results suggest that the derived parameters could provide a simple, non-invasive means for studying the changes in the elastic properties of the vascular system as a function of age.

Youth as an artefact of expertise : problematizing the practice of youth studies in an age of uncertainty

At the start of the 21st century the Liberal democracies, including Australia, are characterized by profound social, economic and cultural transformations. Community, policy and academic discourse is marked by widespread adult anxieties about today’s young people. Representations of youth in the institutional domain of ‘youth studies’ can be conceived as artefacts of the activities of diverse forms of expertise. This paper will focus on the institutionalized processes of abstraction which construct these truths, and the roles played by these processes of abstraction in the restless problematization of ‘youth’ as the object of countless competing and complementary governmental programmes. There has been, in recent years, increased debate about how to do youth studies and how to represent youth. The paper will argue that any rethinking or reassessment of the modes of representing youth ought to take some account of the institutional and abstract nature of these processes of representation, and of the implication of these processes in the regulation of populations of young people; populations which are rendered knowable in all their diversity only through these processes of representation.

Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disorders

The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer.

Uroflow studies in children: Correlation with age, weight and body surface area.

Peak flow rate data (Q(max)) are important for diagnosis of lower urinary tract obstruction. However, the lack of uroflowmetry studies in children, makes their interpretation difficult. With this aim, we studied 167 boys classified in four groups according to their age (G1 : n = 48, 6-7 years; G2 : n = 43, 8-9 years; G3 : n = 37, 10-11 years; G4: n = 39, 12-14 years). We studied in all children, weight, height, body surface area, peak flow rate (Q(max) and the correspondant urinary volume (Vol). Means and standard deviations of Q(max) (ml/sec) were : 15 +/- 5 (G1), 15 +/- 5 (G2), 17 +/- 5 (G3) and 22 +/- 7 (G4) respectively. Corresponding urinary volumes (Vol) (mean standard deviation - in ml) were : G1 = 123 +/- 75; G2 = 122 +/- 79; G3 = 158 +/- 96 and G4 = 162 +/- 101. We found a significant correlation (p < 0,01) between Q(max) and Vol in groups G2, G3 and G4; and between Q(max) and height in groups G1 and G4.The authors demonstrated a positive correlation between maximum flow and voided volume, and an increase of Q(max) with age.

Barshalder 2 : Studies of late Iron Age Gotland

The prehistoric cemetery of Barshalder is located along the main road on the boundary between Grötlingbo and Fide parishes, near the southern end of the island of Gotland in the Baltic Sea. The ceme-tery was used from c. AD 1-1100. The level of publication in Swedish archaeology of the first millennium AD is low compared to, for instance, the British and German examples. Gotland’s rich Iron Age cemeteries have long been intensively excavated, but few have received monographic treatment. This publication is intended to begin filling this gap and to raise the empirical level of the field. It also aims to make explicit and test the often somewhat intuitively conceived re-sults of much previous research. The analyses deal mainly with the Migration (AD 375–540), Vendel (AD 520–790) and Late Viking (AD 1000–1150) Periods. The following lines of inquiry have been prioritised. 1. Landscape history, i.e. placing the cemetery in a landscape-historical context. (Vol. 1, section 2.2.6) 2. Migration Period typochronology, i.e. the study of change in the grave goods. (Vol. 2, chapter 2) 3. Social roles: gender, age and status. (Vol. 2, chapter 3) 4. Religious identity in the 11th century, i.e. the study of religious indicators in mortuary cus-toms and grave goods, with particular emphasis on the relationship between Scandinavian paganism and Christianity. (Vol. 2, chapter 4) Barshalder is found to have functioned as a central cemetery for the surrounding area, located on pe-ripheral land far away from contemporary settle-ment, yet placed on a main road along the coast for maximum visibility and possibly near a harbour. Computer supported correspondence analysis and seriation are used to study the gender attributes among the grave goods and the chronology of the burials. New methodology is developed to distin-guish gender-neutral attributes from transgressed gender attributes. Sub-gender grouping due to age and status is explored. An independent modern chronology system with rigorous type definitions is established for the Migration Period of Gotland. Recently published chronology systems for the Vendel and Viking Periods are critically reviewed, tested and modified to produce more solid models. Social stratification is studied through burial wealth with a quantitative method, and the results are tested through juxtaposition with several other data types. The Late Viking Period graves of the late 10th and 11th centuries are studied in relation to the contemporary Christian graves at the churchyards. They are found to be symbolically soft-spoken and unobtrusive, with all pagan attributes kept apart from the body in a space between the feet of the deceased and the end of the over-long inhumation trench. A small number of pagan reactionary graves with more forceful symbolism are however also identified. The distribution of different 11th cen-tury cemetery types across the island is used to in-terpret the period’s confessional geography, the scale of social organisation and the degree of alle-giance to western and eastern Christianity. 11th century society on Gotland is found to have been characterised by religious tolerance, by an absence of central organisation and by slow piecemeal Christianisation.

Maturation of humoral immune responses : Studies on the effects of antigen type, apoptosis and age

The humoral immune response is dependent on the formation of antibodies. Antibodies are produced by terminally differentiated B cells, plasma cells. Plasma cells are generated either directly from antigen challenged B cells, memory cells or from cells that have undergone the germinal center (GC) reaction. The GC is the main site for class switch, somatic hypermutation and generation of memory cells. Different factors, both internal and external, shape the outcome of the immune response. In this thesis, we have studied a few factors that influence the maturation of the humoral response. We have studied how age affects the response, and we show that responses against thymus dependent antigens (TD) are more affected than responses to thymus independent (TI) antigens, in concordance with the view that the T cell compartment is more affected by age than the B cell compartment. Furthermore, we demonstrate that priming early in life have a big influence on the immune response in the aged individual. Priming with a TI form of the carbohydrate dextran B512 (Dx) induces a reduction of IgG levels in later TD responses against Dx. We have evaluated possible mechanisms for this reduction. The reduction does not seem to be caused by clonal exhaustion or antibody mediated mechanisms. We also showed that the reduced TD response after TI priming can be induced against another molecule than Dx. With the hypothesis that TI antigens induce a plasma cell biased maturation of the responding B cells, we examined the presence of Blimp-1, a master regulator of plasma cell differentiation, in GCs induced by TD and TI antigen. Blimp-1 was found earlier in GCs induced by TI antigen and the staining intensity in these GCs was stronger than in TD antigen induced GCs, indicating that plasma cells might be continuously recruited from these GCs. B cells undergoing the GC reaction are thought to be under a strict selection pressure that removes cells with low affinity for the antigen and also cells that have acquired self-reactivity. We investigated the effect of apoptotic deficiencies on the accumulation of somatic mutations in GC B cells. In mice lacking the death receptor Fas, lpr mice, the frequency of mutations was increased but the pattern of the mutations did not differ from wild type mice. In contrast, mice over-expressing the anti-apoptotic protein Bcl-2, had a lowered frequency of mutations and the mutations introduced had other characteristics.

Validation of age determination methods and growth studies of the sand sole Pegusa lascaris (Soleidae) from the eastern-central Atlantic

[EN]The age and growth of the sand sole Pegusa lascaris from the Canarian Archipelago were studied from 2107 fish collected between January 2005 and December 2007. To find an appropriate method for age determination, sagittal otoliths were observed by surface-reading and frontal section and the results were compared. The two methods did not differ significantly in estimated age but the surface-reading method is superior in terms of cost and time efficiency. The sand sole has a moderate life span, with ages up to 10 years recorded. Individuals grow quickly in their first two years, attaining approximately 48% of their maximum standard length; after the second year, their growth rate drops rapidly as energy is diverted to reproduction. Males and females show dimorphism in growth, with females reaching a slightly greater length and age than males. Von Bertalanffy, seasonalized von Bertalanfy, Gompertz, and Schnute growth models were fitted to length-at-age data. Akaike weights for the seasonalized von Bertalanffy growth model indicated that the probability of choosing the correct model from the group of models used was >0.999 for males and females. The seasonalized von Bertalanffy growth parameters estimated were: L? = 309 mm standard length, k = 0.166 yr?1, t0 = ?1.88 yr, C = 0.347, and ts = 0.578 for males; and L? = 318 mm standard length, k = 0.164 yr?1, t0 = ?1.653 yr, C = 0.820, and ts = 0.691 for females. Fish standard length and otolith radius are closely correlated (R2 = 0.902). The relation between standard length and otolith radius is described by a power function (a = 85.11, v = 0.906)

Age matters in the prevalence and clinical significance of ultra-high-risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS-kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high-risk symptoms in children and adolescents as compared to adults. We examined ultra-high-risk (UHR) symptoms and criteria in a sample of individuals aged 8-40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non-perceptive APS were differentiated. Psychosocial functioning and current non-psychotic DSM-IV axis I disorders were also surveyed. Well-trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8-15-year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non-perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non-perceptive APS, and their interaction with age, also in terms of conversion to psychosis.