Publications

A baseline approach for probabilistic blast risk analysis of building cladding under external explosions

The state of the practice in blast-resistant applications against explosions is to design the structural components for a prescribed combination of explosive mass and location, namely the design basis threat. In this context, the blast source is represented by specific scenarios, mostly associated with expert judgement, rating systems or code provisions. While offering a useful basis for practical applications, the level of detail can be significantly enhanced within a probabilistic framework for risk assessment. In research practice, plenty simplified probabilistic approaches have been proposed on external explosions in order to perform risk assessment. A rigorous methodology for such an assessment is presented herein, using tools and techniques derived from seismic risk-assessment applications. Specifically, the mean annual frequency of different explosive mass hazards is represented via a recurrence law, while the potential locations are modelled as a 2D spatial distribution, accounting for the various layers of defense that exist around the structure, i.e., perimeter protection, landscape, public or private spaces, etc. The methodology is finally substantiated with the case study of a typical building subjected to potential blast loadings from external aggressors.

Propagation of Modelling Uncertainties for Seismic Risk Assessment: The Effect of Sampling Techniques on Low-Rise Non-Ductile RC Frames

Quantifying the impact of modelling uncertainty on seismic performance assessment of existing buildings is non-trivial when considering the partial information available on material properties, construction details, and the uncertainty in the capacity models. This task is further complicated when uncertainty related to ground motion representation is considered. To address this issue, record-to-record variability, uncertainties in structural model parameters, and fragility model parameters due to limited sample size are propagated herein by employing a nonlinear dynamic analysis procedure based on recorded ground motions. A one-to-one sampling approach is adopted in which each recorded ground motion is paired up with a different structural model realization. Uncertainty propagation is explored by measuring the impact of different sampling techniques, such as Monte Carlo simulation with standard random sampling and Latin Hypercube sampling (with Simulated Annealing) in the presence of three alternative nonlinear dynamic analysis procedures: Incremental Dynamic Analysis (IDA), Modified Cloud Analysis (MCA), and Cloud to IDA (a highly efficient IDA-like procedure). This is all illustrated through application to an existing reinforced-concrete school building in southern Italy. It is shown that with a small subset of records, both MCA and Cloud to IDA can provide reliable structural fragility (and risk) estimates for three considered limit states, comparable to the results of more resource-intensive schemes.

Neuroendocrinology of Stress: Implications for Growth and Development

A stressor above a threshold magnitude, or multiple stressors applied simultaneously, cause an organism to alter its behaviour and physiology, with the aim of maintaining homeostasis. The adaptive changes that occur are coordinated and mediated by the stress system in the central nervous system (which includes corticotrophin-releasing hormone and noradrenergic neurons in the hypothalamus and brainstem, respectively), and its peripheral limbs, the hypothalamic-pituitary-adrenal axis and the autonomic (sympathetic) system. Controlled or self-driven challenges to homeostasis and a normally functioning stress system are crucial for normal development and preservation of self and species. In childhood and adolescence, appropriately functioning neuroendocrine responses to stressors are necessary to allow growth and psychosexual maturation to progress normally. Maladaptive neuroendocrine responses, i.e. dysregulation of the stress system, may lead to disturbances in growth and development and cause psychiatric, endocrine/metabolic and/or autoimmune diseases or vulnerability to such diseases, not only during childhood and adolescence, but also in adulthood.

Characteristics of Café-au-lait Macules and their Association with the Neurofibromatosis type I Genotype in a Cohort of Greek Children

Cafe-au-lait macules are the most distinctive clinical finding in neurofibromatosis type I. The aim of this prospective study of Greek children diagnosed with neurofibromatosis type I was to describe the dermatological phenotype and to analyse the characteristics of cafe-au-lait macules and their association with genotype. Pigment intensity and melatonin content of cafe-au-lait macules were measured with a narrowband spectrophotometer. A total of 63 children aged 6 months to 16 years old were studied. Mean melanin content varied, both among patients, and within each patient (p < 0.001). Females had a higher number of cafe-au-lait macules than did males (p = 0.025), and the melanin content of cafe-au-lait macules was lower in females than males (p < 0.001). Patients with protein-truncating variants in the neurofibromatosis type I gene had higher melanin content of cafe-au-lait macules than other types of genetic variants t (55) = 2.196, p = 0.032. Plexiform neurofibromas were also detected in the majority of patients with protein- truncating variants, while juvenile xanthogranulomas were detected equally in patients with protein-truncating and non-protein-truncating variants. In conclusion, cafe-au-lait macules with high melatonin content are associated with patients carrying non-protein-truncating variants. Therefore, measurement of cafe-au-lait macule pigment intensity might provide useful information for initial assessment of patients with neurofibromatosis type I and the severity of their future phenotype.

Figure 3, [Mechanism of aldosterone action on...].

Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews

Abstract Background The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases. Methods We performed a systematic analysis of umbrella reviews ( meta-umbrella ) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations &amp; Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified. Results We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia. Conclusions We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research ( meta-research ).

Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Sexually Abused Girls

de Bellis, Michael D.; Chrousos, George P.; Dorn, Lorah D.; Burke, Lillian; Helmers, Karin; Kling, Mitchel A.; Trickett, Penelope K.; Putman, Frank W. Author Information

Allostatic load and psychological characteristics of transgender individuals. Preliminary case-control findings

External-cause mortality among adolescents and young adults in Greece over the millennium's first decade 2000-09

BackgroundSeveral important socio-behavioral public health problems that either peak or start during the second decade of life contribute to young people's mortality. The aim of this study was to explore patterns, rates, trends and regional variations of external-cause (due to environmental events/circumstances) mortality among young people aged 10–24 years in Greece, over the decade 2000–09.

Major depression and the stress system: A life span perspective

From a transactional developmental perspective, the authors review findings from studies of animals and humans regarding a proposed relation between stress system abnormalities and major depression. The stress system has evolved to promote successful adaptation across the life span, but disruptions in its functioning may increase the risk of pathological outcomes. Emphasis is placed on the role of prenatal and early postnatal experience in contributing to individual differences in postnatal stress reactivity, which may interact with cognitive and psychosocial vulnerabilities to increase susceptibility to later onset of depression. Findings regarding cognitive, psychosocial, and medical sequelae of depression are also reviewed, with a focus on the possible mediating role of the stress system. The authors highlight the importance of multidisciplinary, longitudinal studies in attempting to gain a deeper understanding of the complex developmental processes involved in the onset and course of depression.

Glucocorticoid action : basic and clinical implications

Role of surgery in management of adrenocorticotropic hormone-producing islet cell tumors of the pancreas

Spectrum of LDLR gene mutations, causing familial hypercholesterolemia (FH) in Greece: Un update

Endotoxemia, vitamin D and premature biological ageing in Arab adults with different metabolic states

There are limited studies on the association of endotoxin, a potent mediator of gut-derived inflammation and telomere length (TL). We investigated (1) the influence of adiposity on endotoxin and TL amongst Saudi adults according to type 2 diabetes mellitus (T2DM) status and (2) the influence vitamin D may have on TL attrition. Anthropometric data and fasting blood samples were taken from 775 Saudi adults visiting different primary care centers in Riyadh [387 T2DM and 388 non-T2DM]. TL, derived from peripheral blood mononuclear cells, was analyzed by Quantitative real-time polymerase chain reaction and circulating endotoxin levels by Limulus Amebocyte Lysate assay. Subjects were stratified based on obesity and T2DM status. A significant lower TL was observed in the non-obese T2DM group as compared with their non-obese, non-T2DM counterparts (p = 0.002). Significant inverse associations between TL, endotoxin and endotoxin activity were observed in the cohort with obesity. Regression analysis showed that endotoxin was a significant predictor for TL in all subjects and even after stratification according to subgroups; with variances perceived in circulating TL stronger among non-T2DM obese (10%; p = 0.003) than non-T2DM non-obese (12%; p = 0.007). Also, in the non-T2DM group, TL and HDL-cholesterol predicted 29% of the variances perceived in 25(OH)D (p < 0.001). Taken together these findings show that circulating endotoxin and 25(OH)D are associated with premature biological ageing influenced by adiposity and metabolic state; suggesting future intervention studies to manipulate gut microbiome and or vitamin D levels may offer ways to mitigate premature TL attrition.

Thyroid dysfunction in African trypanosomiasis: a possible role for inflammatory cytokines

Summary OBJECTIVE Sleeping sickness (African trypanosomiasis) is an anthropozoonosis transmitted by the tsetse fly. The treatments of choice are the antiparasitic agents suramin and/or melarsoprol. Experimental infection of animals with Trypanosoma brucei results in inflammatory lesions in the pituitary and/or the thyroid gland. In biochemical terms, these animals have hypothyroidism. We evaluated the functional integrity of the hypothalamic‐pituitary‐thyroid axis in patients with African trypanosomiasis before, during and after specific therapy. DESIGN Prospective, controlled, cross‐sectional study. PATIENTS AND MEASUREMENTS Sixty‐five patients with sleeping sickness (31 female, 34 male; aged 18–66; 32 with haemolymphatic sleeping sickness receiving suramin i.v., 33 with cerebral sleeping sickness receiving melarsoprol) and 13 control subjects (6 female, 7 male; aged 21–60) were enrolled in a cross‐sectional study after giving informed consent. Fourteen patients were studied shortly after admission for sleeping sickness, 19 in the middle of the course of treatment, 18 at the end of the 5‐week treatment period, and 14 patients after cure. All subjects underwent a TRH stimulation test at 1200 with bolus injection of 400 μ g TRH i.v. Blood was drawn for determination of fT3, fT4, TSH, rT3, TNF‐ α , IL‐1 and IL‐6 at 0 minutes and TSH at 60 minutes. All hormones and cytokines were determined by RIA or ELISA. RESULTS Baseline TSH concentrations (mean ± SEM) were elevated in unmedicated patients with sleeping sickness compared to normal subjects (2.6 ± 0.4 vs 1.4 ± 0.2 mU7l; P = 0.01), whereas f T3 (2.7± 0.5 vs 5.8 ± 0.3 pmol/l; P = 0.0002) and fT4 concentrations (10.3 ± 1.2 vs 15.4 ± 0.8 pmol/l; P = 0.007) were low. Stimulated TSH concentrations did not significantly differ from normal controls. Reverse T3 concentration in patients with sleeping sickness were normal (2.2 ± 0.3 vs 2.4 ± 0.2 nmol/l; P = NS). During the course of treatment, baseline TSH, f T3 and fT4 concentrations slowly returned to normal and were indistinguishable from controls after cure. Plasma concentrations of TNF‐α (16.0 ± 4.1 vs 2.9 ± 1.4 ng/l in controls; P=0.003) and interleukin‐6 (19.2 ± 7.3 vs 1.3 ± 0.2 ng/l; P = 0.0001), but not interleukin‐1 β (2.0 ± 0.2 vs 0.9 ± 0.2, ng/l P = NS), were elevated, when thyroid function impairment and disease activity were at their maximum, but gradually decreased into the normal range with therapy. We found a negative correlation between baseline cytokine concentrations and fT3 concentrations (TNF‐α: r = 0.34, P = 0.003; IL‐6: r =–0.43, P = 0.0001). CONCLUSIONS We conclude that unmedicated sleeping sickness is associated with significant impairment of thyroid function, which is reversed with specific therapy. Elevated TSH concentrations and low f T3 and f T4 concentrations suggest primary hypothyroidism in patients with sleeping sickness. However, an additional pituitary and/or hypothalamic component cannot be excluded. This impairment may be due to the elevated plasma cytokine concentrations found in these patients or may be the result of parasitic thyroiditis.

Seismic performance of a steel moment-resisting frame subject to strength and ductility uncertainty

The reliable estimation of the seismic performance of structures requires quantifying the aleatory and epistemic uncertainties of the system parameters. This is efficiently achieved for a case study of a four-story steel moment-resisting frame through several important advances. First, a state-of-the-art numerical model is formed with full spatial parameterization of its strength and plastic deformation properties. Empirical relationships derived from experimental data are used to model the cyclic behavior of steel sections using probabilistically distributed parameters that include intra- and inter-component correlation. Finally, incremental dynamic analysis and Monte Carlo simulation are employed to accurately assess the seismic performance of the model under the influence of uncertainties. Of interest is the extent to which model parameter uncertainties may trigger negative demand-capacity correlation in structural fragility evaluation, where, for example, a lower ductility capacity for a component may decrease the threshold for local failure while at the same time raising the local demand estimate from an uncertainty-aware model. With respect to the examined steel moment-resisting frame and considering three construction quality levels (i.e. very good, average, low) as per FEMA P-58, it is shown that, despite the good agreement of the evaluated structural demands obtained with and without consideration of the model parameter uncertainties for well-designed modern buildings, the potential demand-capacity correlation is likely to give rise to unconservative estimates of fragility for local damage-states, especially in cases where substandard quality control is exercised during construction.

Children with Classic Congenital Adrenal Hyperplasia Have Elevated Serum Leptin Concentrations and Insulin Resistance: Potential Clinical Implications

Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P < 0.001) and testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dl, P = 0.003) concentrations. Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear regression analysis indicated that serum leptin concentrations were best predicted by BMI in both patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients with CAH may further enhance adrenal and ovarian androgen production, decrease the therapeutic efficacy of glucocorticoids, and contribute to later development of polycystic ovary syndrome and/or the metabolic syndrome and their complications.

Vitamin D Receptor Polymorphisms in Hypocalcemic Vitamin D-Resistant Rickets Carriers

&lt;i&gt;Background/Aims:&lt;/i&gt; Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, secondary hyperparathyroidism, elevated levels of 1,25-dihydroxyvitamin D&lt;sub&gt;3&lt;/sub&gt; [1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt;], and occasionally, alopecia. In most cases, the disease is associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; action. The apparently healthy HVDRR heterozygotes express both normal and mutant VDR alleles, and they present higher levels of 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; than their respective controls. Because VDR function, except for the disease-causative mutations, might be influenced by the presence of certain polymorphisms, we investigated the distribution of four common VDR polymorphisms –&lt;i&gt; Bsm&lt;/i&gt;I, &lt;i&gt;Apa&lt;/i&gt;I, &lt;i&gt;Taq&lt;/i&gt;I and &lt;i&gt;Fok&lt;/i&gt;I – in HVDRR carriers compared with their respective controls. &lt;i&gt;Methods:&lt;/i&gt; Sixty-seven relatives of 2 HVDRR patients, all members of an extended Greek kindred, were included in the study. VDR allelic polymorphisms were assessed by restriction fragment length polymorphisms after specific polymerase chain reaction amplification. &lt;i&gt;Results:&lt;/i&gt; The distribution of genotypic and allelic frequencies differed between HVDRR carriers and their respective controls regarding &lt;i&gt;Bsm&lt;/i&gt;I and &lt;i&gt;Taq&lt;/i&gt;I polymorphisms. The bb genotype and the T allele (presence of &lt;i&gt;Bsm&lt;/i&gt;I and absence of &lt;i&gt;Taq&lt;/i&gt;I polymorphisms) were less frequent in the HVDRR carrier group than in the control group in a statistically significant manner (p = 0.029 and p = 0.025, respectively). &lt;i&gt;Conclusions:&lt;/i&gt; Our findings showed that the apparently healthy HVDRR carriers present a different distribution of &lt;i&gt;Bsm&lt;/i&gt;I and &lt;i&gt;Taq&lt;/i&gt;I VDR polymorphisms than their controls, suggesting that further investigation of the HVDRR carrier population may elucidate the implication of VDR alleles in VDR function and the vitamin D endocrine system.