Challenges in the Delivery Room: Integrated Analysis of Biomarkers Predicting Complications in Lupus Pregnancy

Pregnancy in autoimmune rheumatic diseases remains a real challenge in clinical practice due to complex interplay between disease activity, pregnancy and drugs, and account for potential influence of pregnancy on rheumatic condition and the impact of disease on pregnancy outcomes. Indeed, innovative and successful therapies have dramatically improved the quality of life in immune-mediated rheumatic conditions and, subsequently, allowed more patients of reproductive age to plan a pregnancy/to conceive. The purpose of this chapter is to discuss emerging data about the interaction of pregnancy and systemic erythematosus lupus (SLE) focusing on modulation of the immune system by pregnancy, pregnancy outcomes in women with active lupus, biomarkers of adverse pregnancy outcomes (APO) including predictors of pre-eclampsia, predictors of obstetric complications in SLE, the influence of autoantibodies on fetal health, and, finally, evidence about rheumatologic and obstetric follow-up. There are still unmet needs in this new field of reproductive rheumatology and it becomes crucial that researchers, physicians (rheumatologists, specialists in maternofetal medicine, obstetricians) and midwifes share their knowledge and expertise in counseling women with SLE wishing to conceive, assisting pregnancy and managing different issues related to APO as well as drug optimization in preconception, during pregnancy and postpartum period

Cyclotron resonance in HgTe/CdTe-based heterostructures in high magnetic fields

Cyclotron resonance study of HgTe/CdTe-based quantum wells with both inverted and normal band structures in quantizing magnetic fields was performed. In semimetallic HgTe quantum wells with inverted band structure, a hole cyclotron resonance line was observed for the first time. In the samples with normal band structure, interband transitions were observed with wide line width due to quantum well width fluctuations. In all samples, impurity-related magnetoabsorption lines were revealed. The obtained results were interpreted within the Kane 8·8 model, the valence band offset of CdTe and HgTe, and the Kane parameter E(P) being adjusted

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the fi

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.Peer reviewe

Application of Local Axial Flaps to Scalp Reconstruction

BackgroundScalp defects may be caused by various etiological factors, and they represent a significant surgical and aesthetic concern. Various surgical techniques can be applied for reconstructive work such as primary closure, skin grafting, pedicled or free flaps. In this article, the authors share their clinical experience with scalp operations using the technique of local flaps and discuss the application of this method from the perspective of not only the size of the defect, but also in relation to the anatomical area, quality of surrounding tissue, and patient's condition.MethodsDuring the period from December 2007 to December 2012, 13 patients with various scalp defects, aged 11 to 86 years, underwent reconstruction with local pedicle flaps. The indications were based on the patients' condition (age, sex, quality of surrounding tissue, and comorbidities) and wound parameters. Depending on the size of the defects, they were classified into three groups as follows: large, 20 to 50 cm2; very large, 50 to 100 cm2; extremely large, 100 cm2. The location was defined as peripheral (frontal, temporal, occipital), central, or combined (more than one area). We performed reconstruction with 11 single transposition flaps and 1 bipedicle with a skin graft on the donor area, and 2 advancement flaps in 1 patient.ResultsIn all of the patients, complete tissue coverage was achieved. The recovery was relatively quick, without hematoma, seroma, or infections. The flaps survived entirely.ConclusionsLocal flaps are widely used in scalp reconstruction since they provide healthy, stable, hair-bearing tissue and require a short healing time for the patients

Broader-based Growth Resilient to Global Uncertainties

Under favourable external conditions, the economies of the New EU Member States (NMS) fared even better in the first quarter of 2006 than in 2005. Investment accelerated sharply and industry is proving buoyant. Labour productivity has registered strong gains, unit labour costs declined. This is one of the reasons for the highly successful expansion of foreign trade, the second being the ongoing upgrading of exports and production. Foreign trade contributed positively to overall growth in Central European NMS already in 2005. In 2006, the growth contributions of both consumption and investment are also rising, thus making room for a more balanced overall GDP growth. Industrial production will continue to expand rapidly in 2007, also on account of robust domestic consumption and investment growth. With the exception of Hungary, fiscal policy will not interfere substantially with real growth. Trade expansion is likely to be supported by the continuing gains in unit labour costs. Weaker growth in the EU-15 will not restrict NMS exports too much also in view of ongoing structural changes and quality improvements in both NMS production and exports. The generally positive outlook for the next two years assumes an absence of major turbulence on the exchange rate markets. This assumption is not risk-free - especially where Hungary is concerned. It is to be hoped that the recently announced fiscal consolidation programme proves credible and pre-empts excessive adjustments. The labour market situation is improving across most NMS and accession countries as accelerated GDP growth has at last started to generate more substantial job creation. Migration to the UK and Ireland after accession was also significant, both in magnitude and in its effects on the sending countries, in the cases of Poland, Slovakia, Lithuania and Latvia. The effects on the UK and Ireland of migration from these countries have so far been modest but broadly positive. We expect similar outcomes for the next enlargement that will bring in Romania and Bulgaria. Growth, driven primarily by domestic demand, is expected to continue to be strong throughout Southeast Europe. The external balances should deteriorate due to strong demand for imports, which is sustained by exchange rates that are appreciating in real terms. Macroeconomic stability will be maintained, though inflation is picking up; and is a serious problem in Serbia and Romania. Inflation is a major concern in Turkey, as is macroeconomic stability more fundamentally. At the end of 2006 it should be decided whether Bulgaria and Romania will join the EU on 1 January 2007, as is widely expected; whether the EU will start negotiations with Macedonia, which at the moment seems unlikely; whether the other Western Balkan countries will sign Stabilization and Association Agreements with the EU; and what is the EU¿s strategy for further enlargement. The momentum has been lost when it comes to the Balkans, but the accession of Bulgaria and Romania and later on of Croatia may still make it possible for the rest of the Balkans to join the EU by 2015. Russian GDP growth is slowing down as the real sector weakens. Domestic demand is strong, yet the contribution of net exports to GDP growth is negative. Nominal exports are booming thanks to the high prices of energy and metals. Paris Club debt repayments are ahead of schedule. GDP growth will be about 6% in both 2006 and 2007; disinflation will be only gradual. The restructuring and institutional reforms are running late. WTO accession may be postponed yet again; it is unclear what course future EU Russia relations will take. In Ukraine the slowdown in economic growth has been reversed in 2006; domestic demand has picked up. But exports are performing badly, and the current account is expected to switch to a deficit. The hike in gas prices in early 2006 did not have any sizeable impact on the economy, not least because it has yet to be fully passed on to the final consumers. However, given the planned tariff hikes, inflation is expected to remain in double digits. The new government is likely to be less inclined to implement liberal reforms and its stability is questionable. The Chinese economy has kept fast growth in the first quarter of 2006. The expansion was mainly driven by a surge of investment and supported by a record foreign trade surplus. Private consumption developed at a stable pace, inflation remained low. Government measures to dampen growth and to prevent an overheating of the economy may become more effective in the near future. Nevertheless, we expect GDP growth close to 10% in both 2006 and 2007

Back from the Peak, Growth in Transition Countries Returns to Standard Rate of Catching-up

In its new special issue on the economies of Central, East and Southeast Europe, The Vienna Institute for International Economic Studies (wiiw) analyses the current economic situation in the region as well as development prospects for 2005 and 2006, presenting revised forecasts based on results for the first months of 2005. Brief surveys of the individual countries are added (covering Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Hungary, Macedonia, Poland, the Slovak Republic, Slovenia, Serbia and Montenegro, Romania, Russia, Turkey, Ukraine, and China). A short analysis of the ongoing dispute related to the EU budget 2007-2013 as well as an annex with selected indicators of competitiveness and projections of per capita GDP until 2015 are attached. The high growth recorded in 2004 has been generally slowing down in the first months of 2005. The average GDP growth rate for the eight new EU member states (NMS) in the first quarter of 2005 dropped by 2.5 percentage points (to 3.3%), compounded by a marked deterioration of growth in Poland. The growth slowdown is associated with a slow expansion of gross fixed investment; massive declines in the rates of growth of industrial production; quite an abrupt deterioration in industrial labour productivity; and real currency appreciation and a resulting strong rise in unit labour costs. Despite this (and despite growth being weaker than expected in the euro zone), NMS foreign trade continues to perform excellently. Foreign trade has been even more instrumental in generating GDP growth in the first quarter of 2005 than in the past. It should be pointed out, however, that NMS trade with the 'old' EU has grown at a relatively slower pace. The first quarter results confirm our previous assessment of the medium-term prospects in the NMS. GDP growth will generally decelerate to below 4% on average in 2005; it will most probably not accelerate too much in 2006. Given the relatively poor economic performance in the euro zone, there is little that the otherwise constrained fiscal or monetary policies in the NMS can do to change this situation. Much more will depend on the corporate sector's willingness to invest. Growth in 2005 is also slowing down in Southeast Europe - particularly among the region's largest economies Turkey, Romania, Croatia and Serbia. Fiscal consolidation and increasing trade deficits will thus hamper growth which over the biennium 2005-2006 will nonetheless range between 4 and 6%. Only in Croatia will growth be weaker. The prospects for further EU enlargements have taken a turn for the worse in the wake of the recent EU 'constitutional' and budget crises. That notwithstanding, the accession of Bulgaria and Romania is beyond dispute, possibly with a one-year delay. Despite high world market commodity prices, the robust growth in Russia may be a thing of the past. Already in 2004 investment growth was disappointing, reflecting high uncertainty and the deteriorating investment climate. Lagging reforms and huge structural imbalances blur the prospects for sustainable long-term growth. The stimulation of domestic demand through a fiscal relaxation will protract disinflation and induce real appreciation. This will be conducive to higher imports, a lower trade surplus and eventually to slower GDP growth. Following Ukraine's recent explosive growth, things are settling down somewhat, despite some fiscal relaxation. Currency appreciation has adversely affected the trade surplus, while the investment climate has been poisoned by rumours of re-nationalization and the lacklustre programme of the new government. China continues to register extremely rapid GDP growth, despite some slowdown in investment growth. Private consumption is picking up and net exports are rising faster than expected