Changes of 27% in cohesion and 8% in the friction angle were foun

Changes of 27% in cohesion and 8% in the friction angle were found due to the attack of the interface and consequences of the changes are examined. Crown Copyright (c) 2013 Published by Elsevier Ltd. All rights reserved.”
“Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a 3 variety of different treatment conditions. Numerical calculations using animal

models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse click here model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric

fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases. (C) 2014 AIP Publishing LLC.”
“Treatment of osteoporotic fractures with conventional surgical methods is associated with a high rate of complications. Intense search for new treatment options includes SN-38 in vitro https://www.selleckchem.com/products/Cyt387.html development of specific biomaterials aimed to be part of the surgical armamentarium. Strontium doped calcium phosphate spheres (SrCPS) is a new material that might be of interest due to the influence on osteoclast and osteoblast activity. In the present study, we successfully constructed hollow spherical SrCPS particles with a diameter of approximate to 700 nm and shell thickness

of approximate to 150 nm. The Sr content was about 20 wt %. Cell viability and cytotoxicity were investigated in vitro with concentrations from 0 to 1000 g/mL of SrCPS in medium extract in a day chase study. The in vivo biocompatibility was tested in a delayed bone-healing model in a rat vertebral defect by histology, CT, and nanoSPECT. The SrCPS showed no toxicity in vitro with comparable cell number in all concentrations. Increased metabolism was seen in the cell viability study in cells exposed to 400 and 600 g/mL. SPECT showed good biocompatibility with no local adverse effects and an increased osteoblast activity as compared to adjacent vertebra. SrCPS implantation induced bone formation and resulted in complete resorption and defect consolidation. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

For each theme, we calculated the rate of patients who discontinu

For each theme, we calculated the rate of patients who discontinued a trial from the total number of dropouts in each trial. The rates obtained with different trials were combined using a random effects model. We also performed a random effects meta-regression analysis to identify sources associated with the rates.\n\nResults: Overall, 259 432 studies consisting of 266 trials and 13,593 patients were included in the analysis. From these, we short-listed 54 attrition reasons and identified 21 key themes. “Ineffectiveness” and “adverse event” were the reasons frequently reported by >5% of the dropouts. On further investigation of the theme ineffectiveness, the attrition compound inhibitor rate was associated

with delivery routes of treatment, trial duration, flare design,

prohibition of usual analgesics, and allowing the use of GM6001 nmr escape medication. In cases of adverse events, we found that the treatment type and delivery route affected the attrition rate.\n\nConclusions: Our findings not only support the importance of the intention-to-treat analysis, but also suggest the possibility of controlling the attrition at the study level. (c) 2013 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:346-354″
“Tuberculosis (TB) services in China are provided through a large network of TB dispensaries. Even though hospitals are not as well placed to follow recommended standards of TB care, a significant proportion of people with TB symptoms seek care from hospitals. In spite of having a policy and mandate in place, the Ministry of Health had little success in encouraging hospitals to refer suspected TB cases to dispensaries. Following the epidemic of severe acute respiratory syndrome in 2003, the government set up a nationwide Internet-based communicable diseases reporting system. This achieved productive collaboration between hospitals and TB dispensaries. From 2004 to 2007, the percentage of TB suspects and patients needing referral from hospitals who arrived in TB dispensaries increased substantially from 58.7% to 77.8% and the contribution of hospitals to selleck chemical diagnosing sputum smear-positive TB cases doubled

from 16.3% to 32.9%. Using the Internet-based reporting system, hospitals in China contributed to finding about one third of all sputum smear-positive TB cases and helped meet the global TB control target of detecting 70% of such cases. Based on the data available from routine surveillance facilitated by this Internet-based system, this paper details the process and outcomes of strengthening collaboration between hospitals and TB dispensaries using the Internet as a tool and its potential application to other country settings.”
“The influence of a thin carbonate-containing hydroxyapatite (CA) coating to tetragonal zirconia polycrystal (TZP) on osteoblast-like cell response was investigated. TZP disks were subjected to blasting and acid etching.

However, recent advances in Bayesian experimental design together

However, recent advances in Bayesian experimental design together with increased computing power allow to optimize the measurement strategy ‘on-the-fly’, taking into account the results of previous measurements to select the best energy for the next measurement and to compute the expected information gain from further measurements. As example depth profiling of Deuterium in tungsten is presented and the results of the different measurement strategies are compared. (C) 2010 Elsevier B.V. All rights reserved.”
“Background: Anticonvulsants require special consideration particularly at

the interface from Cilengitide mouse hospital to ambulatory care.\n\nPatients and method: Observational study for 6 months with prospectively enrolled consecutive patients in a neuropediatric ward of a university hospital (age 0-<18 years) with long-term therapy of at least one anticonvulsant. Assessment of outpatient prescriptions after discharge. Parent interviews for emergency treatment for acute

seizures and safety precautions.\n\nResults: We identified changes of the brand in 19/82 (23%) patients caused by hospital’s discharge letters (4/82; 5%) or in ambulatory care (15/82; 18%). In 37/76 (49%) of patients Screening Library cost who were deemed to require rescue medication, no recommendation for such a medication was included in the discharge letters. 17/76 (22%) of the respective parents 123 stated that they had no immediate access to rescue medication. Safety precautions were applicable in 44 epilepsy patients. We identified knowledge deficits in 27/44 (61%) of parents.\n\nConclusion: Switching of brands after discharge was frequent. In the discharge letters, rescue medications were insufficiently recommended. Additionally, parents frequently displayed knowledge deficits in risk management.”
“The effects of azadirachtin A added to

the sucrose diet of the adult females on the mortality, Napabucasin JAK/STAT inhibitor oviposition, and hatching of the sand fly vector of American visceral leishmaniasis Lutzomyia longipalpis (Lutz & Neiva, 1912) were investigated. Concentrations of 0.1, 1.0, and 10.0 mu g/mg of azadirachtin significantly increased insect mortality in comparison with control insects. The same dose also significantly reduced oviposition but not hatching. After a long development period, significantly fewer adult insects were obtained from eggs hatching by azadirachtin-treated females in a dose-response manner. These results indicate that azadirachtin is a potent sterilizer that could be used against the development of Lu. longipalpis populations and as a tool for studying physiological and biochemical processes in phlebotomine species.”
“BACKGROUND: Treatment of patients with extrahepatic artery aneurysms (HAAS) is not well defined. The aim of this study was to report 4 patients with HAAS treated by ligation and to underline the rationale of this technique.

Each principle is organized around three parts: (1) a brief descr

Each principle is organized around three parts: (1) a brief description; (2) relevance to landscape ecological

research; and (3) recommended research topics. Using these principles, I suggest potential avenues to advance landscape ecological research about biodiversity, ecosystem services, and human well-being.”
“We have determined the technological properties of four lines containing combinations of three HMW-GS transgenes, encoding HMW-GS 1Ax1, 1Dx5 and 1Dy10L These lines were produced by conventional crossing A 1331852 of three single transgenic lines of the bread wheat cultivar Anza that contains the endogenous HMW-GS pairs 1Dx2 + 1Dy12 and 1Bx7* + 1By8 and is null for the Glu-A1 locus. Consequently, the total number of HMW-GS ranged from 4 in the control line Anza to 7 in line T618 which contains all three HMW-GS transgenes. The lines

were studied over two years using a range of widely used grain and dough testing methods. MRT67307 All lines with transgenic subunits showed higher levels of glutenin proteins than the Anza control, and these differences were highly significant for lines T616, T617 and T618, containing, respectively, the transgenes encoding HMW-GS 1Ax1 and 1Dy10, 1Dx5 and 1Dy10 and 1Ax1, 1Dx5 and 1Dy10. These increases in glutenin levels are compensated by lower levels of gliadins present in transgenic lines. These changes affected the ratio of polymeric to monomeric gluten proteins (poly:mono), the ratio of HMW-GS to LMW-GS (HMW:LMW) and the contents of individual 1Ax, 1Bx, 1By, 1Dx and 1Dy subunits. Transgenic lines expressing subunit 1Dy10 together with x-type subunits (T616, T617 and T618) were superior to line T606, which selleck chemical had only increases in x-type subunits. In particular, the combination of transgenic subunits 1Dx5 and 1Dy10 (line T617) gave better dough theological properties than the other combinations of transgenic subunits. For example, dough development time and stability were increased by 3.5-fold and 8.5-fold, respectively, while the mixing tolerance index (MTI) was decreased by 3.3-fold in line T617 with respect to the control line. Alveograph analyses showed that all four transgenic

combinations had increased P values compared to the Anza control but subunit 1Dx5 greatly reduced the extensibility (L). These results show that stacking HMW-GS transgenes by conventional crossing is a valid strategy for the improvement of wheat quality, with different effects being related to the different HMW-GS combinations. (c) 2009 Elsevier Ltd. All rights reserved.”
“One of the challenges facing farmers today is to ensure adequate integration of natural resources into animal feeds. The aim of the present study is to evaluate the effects of Khaya senegalensis (KS) leaves on the performance of growing male rabbits, carcass traits and biochemical as well as hematological parameters. Thirty New Zealand White male growing rabbits were randomly divided into 3 groups (10 rabbits per group).

Results and conclusion: Significant differences in genotype,

\n\nResults and conclusion: Significant differences in genotype, allele and haplotype frequencies of PRNP 1368 polymorphism were not observed between AD and normal controls. There were no significant differences

in the genotype and allele frequencies of the PRNP 1368 polymorphism between Korean VaD patients Selleckchem GDC-941 and normal controls. However, in the haplotype analysis, haplotype Ht5 was significantly over-represented in Korean VaD patients. This was the first genetic association study of a polymorphism outside the coding region of PRNP in relation to AD and VaD.”
“Manganese superoxide dismutase (leMnSOD) cDNA was cloned from the Antarctic bivalve Laternula elliptica. The full-length cDNA of leMnSOD is 1238 bp in length and 432 contains an open reading frame of 681 bp encoding 226 amino acid residues including a putative mitochondrial

targeting peptide of 26 amino acids in the N-terminal region. The calculated molecular mass is 24.8 kDa with an estimated isoelectric point of 6.75. leMnSOD signatures from 185 to 192 (DVWEHAYY) and four conserved amino acids (H52, H11, D185, and H192) responsible for binding manganese were observed. Sequence comparison showed that leMnSOD had high levels of identity with MnSOD from Haliotis discus discus, Mizuhopecten yessoensis, and Crassostrea gigas (68%, 66%, and 59%, respectively). RT-PCR analysis revealed the presence of leMnSOD transcripts in all tissues examined. Quantitative real-time selleckchem RT-PCR assay indicated that treatment with polychlorinated biphenyls (PCBs) significantly increased leMnSOD mRNA expression in an organ-, time-, and dose-dependent manner. The mRNA expression with exposure to PCBs at 0.1

and 10 ppb reached the highest level at 6 h and then recovered slightly from 6 to 48 h in the gill. In contrast, the expression of leMnSOD mRNA showed a find more different expression pattern related to PCB concentration in the digestive gland. The mRNA expression at 0.1 ppb PCBs increased up to 12 h and then decreased by 48 h, but increased immediately at 10 ppb PCBs. The leMnSOD was overproduced in Escherichia coli and purified. The recombinant leMnSOD showed maximum activity at pH 9.0, and it retained more than 50% of its original activity after incubation for 30 min at 40 degrees C. (C) 2009 Elsevier Ltd. All rights reserved.”
“This study was performed to test whether children born small for gestational age (SGA) with catch-up growth (CUG) could be associated with the early development of insulin resistance and the beta-cell dysfunction and to explore the impacts of height CUG and weight CUG on the insulin resistance in a Chinese population.

Several possible surgical approaches were considered, including a

Several possible surgical approaches were considered, including a transsylvian approach and a contralateral interhemispheric approach. #432 randurls[1|1|,|CHEM1|]# Ultimately, the patient underwent a contralateral interhemispheric

trans-striatocapsular approach to the lesion and was discharged without neurologic deficit within 72 hours.\n\nCONCLUSION: The approach described here is a novel alternative to transsylvian or supracarotid approaches to the anterior inferior basal ganglia and in this patient provided a well-tolerated surgical corridor that allowed complete resection of his cavernoma. We discuss several advantages and disadvantages of the various approaches to the anterior inferior basal ganglia.”
“Early lymphocyte recovery following auto-SCT for non-Hodgkin’s lymphoma (NHL) has been reported to be associated with improved outcome. The significance of early lymphocyte recovery following a stem cell transplant in NHL

subtype diffuse large B-cell lymphoma (DLBCL) in the rituximab era remains unclear. Patients who underwent an auto-SCT at our institution for DLBCL during the time period 1998-2008 (n=115) selleck screening library were included in the study. Patient characteristics were well-balanced in both rituximab naive and rituximab-exposed groups. Prior rituximab therapy did not affect lymphocyte recovery on day 14 or day 28. Lymphocyte recovery on day 14 and day 28 and prior rituximab had no impact on survival after auto-SCT for DLBCL, despite early benefit. Other factors such as age, stage at presentation, number of salvage

regimens, mobilization procedure, conditioning regimen, pre-transplant radiation therapy and pre-transplant disease status had no impact on survival. Our data showed that the survival benefit with early lymphocyte recovery and prior rituximab seen in previous reports may be lost with longer follow-up. Prior rituximab therapy does not appear to influence the lymphocyte count at days 14 and 28 following auto-SCT. Our findings suggest that future trials should consider manipulating the immune system as a post transplant intervention to improve long-term outcome. Bone Marrow Transplantation (2012) 47, 82-87; doi: 10.1038/bmt.2011.29; published learn more online 28 February 2011″
“Secondary hyperparathyroidism (SHPT) may contribute to the systemic illness that accompanies chronic heart failure (CHF). Healthy elderly with vitamin D deficiency who did not develop hyperparathyroidism (functional hypoparathyroidism, FHPT) had lower mortality than those who did. This study was designed to examine determinants of the PTH response in the vitamin D insufficient CHF patients. Sixty five vitamin D insufficient males with NYHA class II and III and 20 control subjects age >= 55 years were recruited. Echocardiography, physical performance, NT-pro-BNP, PTH, 25-hydroxyvitamin D (25(OH) D), adiponectin and bone activity surrogate markers (OPG, RANKL, OC, beta-CTx) were assessed.

However, recent reports have shown that injuries to posterior str

However, recent reports have shown that injuries to posterior structures, the cerebellum in particular, may have a role in language processing. Herein, we

will look first at the linguistic role of the cerebellum in light of the literature, then of the thalamus and some described clinical syndromes, and finally, specific syndromes resulting from occipital lobe lesions, all of which are supported by the posterior vascular system. The human brain is such Selleck MLN8237 a complex organization that in addition to the thalamus and occipital cortex, we can see the involvement of the cerebellum in high cognitive functions. Posterior system strokes may lead to clinical findings of cognitive deficits, including neurolinguistic components. Determining these defects in stroke patients may precipitate changes in current management strategies.”
“Electrochemical polymerization of acacia gum (AG) was initiated by electroactive polyaniline (PANI) monomers by radical cation formation and their coupling reactions with AG molecules. R(CT) values obtained from electrochemical impedance spectroscopy analysis at various AG

concentrations with PANI were drastically decreased, confirming formation of conducting AG complexes with PANI. Quantitative analysis of ochratoxin-A (OTA) detection in electrolyte was carried out on rabbit antibody-immobilized PANI and PANI-AG matrices. The observed sensitivities of 50, 150, and 250 mg AG-added PANI matrix-based platforms

were 3.3 +/- 0.5, 10.0 +/- 0.5, and 12.7 +/- 0.5 mu A/ng/ml, respectively. The sensitivity of selleck compound only PANI electrodes was 2.6 +/- 0.3 mu A/ng/ml, which was relatively lower than AG-added PANI. This increase was due to the presence of glycan functional groups in AG molecules that supported the retention of activity of antibodies. In addition, enhanced electron transportation at AG-PANI film surface was observed due to formation of an electroactive polymer film of two different electroactive functions to contribute toward Selleck GSI-IX enhancement in the detection sensitivity. (C) 2010 Elsevier Inc. All rights reserved.”
“A series of quinolines, including chloroquine and quinine, were identified as potent pigmentation inhibitors through screening a compound library in murine melanocytes. Structure-activity relationship analysis indicated that 4-substituted amino groups with a tertiary amine side chain, such as chloroquine, were associated with robust inhibitory activity. In contrast to many 3 previously identified pigmentation inhibitors, these newly identified inhibitors had no effect on either the level or the enzymatic activity of tyrosinase, the rate-limiting enzyme in melanin production. Rather, our results showed that these quinolines inhibited melanogenesis by disrupting the intracellular trafficking of tyrosinase-related proteins and lysosome-associated membrane protein 1 (Lamp-1).

For the continuous grazing system, sheep grazed the same plots ea

For the continuous grazing system, sheep grazed the same plots each year, and for the alternating system, grazing and hay making were

alternated annually between two adjacent plots. In July, August, and September 2009 and 2010, feed intake and live weight of sheep were Acalabrutinib price determined. The GS did not affect dOM (P=0.101), OMI (P=0.381), and LWG of sheep (P=0.701). Across both GS LWG decreased from 98 g . d(-1) for GI1 to 62 g . d(-1) for GI6 (P smaller than 0.001; R-2=0.42). There were no interactions between GS and GI for all measured parameters (P bigger than = 0.061), indicating that alternating grazing did not compensate for negative effects of heavy grazing even after 4 yr of grassland use. In summary, our study showed that irrespective of GI, alternating grassland use does not improve dOM, OMI, and hence, LWG of sheep. However, it Belnacasan might enhance revenues and ecological sustainability in the long term when compared to the common practice of continuous grazing at very high stocking rates.”
“Assortative mating, an ubiquitous form of nonrandom mating, strongly impacts Darwinian fitness and can drive biological diversification. Despite its ecological and evolutionary importance, the behavioural processes underlying assortative mating are often unknown, and in particular, mechanisms not involving mate choice

have been largely ignored so far. Here, we propose that assortative mating can arise from prudent habitat choice’, a general 4 mechanism that acts under natural selection, and that it can occur despite a complete mixing of phenotypes. We show that in the

cichlid Eretmodus cyanostictus size-assortative mating ensues, because individuals of weaker competitive ability SB203580 molecular weight ignore high-quality but strongly competed habitat patches. Previous studies showed that in E.cyanostictus, size-based mate preferences are absent. By field and laboratory experiments, here we showed that (i) habitat quality and body size are correlated in this species; (ii) territories with more stone cover are preferred by both sexes in the absence of competition; and (iii) smaller fish prudently occupy vacant territories of worse quality than do larger fish. Prudent habitat choice is likely to be a widespread mechanism of assortative mating, as both preferences for and dominance-based access to high-quality habitats are generic phenomena in animals.”
“INTRODUCTION: Activation of renal sympathetic nerves is associated with the development of hypertension. Catheter-based renal sympathetic denervation with radiofrequency energy ablation is a new promising treatment option for resistant hypertension. We here report the first Danish experiences and results with this technique.\n\nMATERIAL AND METHODS: Nine patients with resistant hypertension and a day-time 24-hour ambulatory blood pressure (BP) of 152/89 mmHg +/- 10/10 (standard deviation) mmHg despite treatment with 5.4 +/- 1.

In this study, two types of relays are considered Conventional a

In this study, two types of relays are considered. Conventional amplify and forward relays AZD8055 manufacturer in which all relays amplify their received signal and forward it to the destination in a round-robin fashion. In addition, decode and forward relays in which the relays that correctly detect the source signal will forward the corresponding fading gain to the destination in pre-determined orthogonal time slots are studied. The optimum decoder for both communication systems is derived and performance analysis are conducted. The exact average bit error probability (ABEP) over Rayleigh fading channels is obtained in closed-form for a source equipped

with two transmit antennas and arbitrary number of relays. Furthermore, simple and general asymptotic expression for the ABEP is derived and analyzed. Numerical results are also provided, sustained by simulations which corroborate the exactness see more of the theoretical analysis. It is shown that both schemes perform nearly the same and the advantages and disadvantages

of each are discussed.”
“Development of assays to screen milk for economically motivated adulteration with foreign proteins has been stalled since 2008 due to strong international reactions to the melamine poisoning incident in China and the 4 surveillance emphasis placed on low molecular weight nitrogen-rich adulterants. New screening assays are still needed to detect high molecular weight foreign protein adulterants and characterize this understudied potential risk. A rapid turbidimetric method was developed to screen milk powder for adulteration with insoluble plant proteins. Milk powder samples spiked with 0.03-3% by weight of soy, pea, rice, and wheat protein isolates were

extracted in 96-well plates, and resuspended pellet solution absorbance was measured. Limits of detection ranged from 100 to 200 mu g, or 0.1-0.2% of the sample weight, and adulterant pellets were visually apparent even at similar to 0.1%. Extraction recoveries ranged from 25 to 100%. Assay sensitivity and simplicity indicate that it would be ideally suitable to rapidly screen milk samples in resource selleck chemicals poor environments where adulteration with plant protein is suspected.”
“BackgroundAlopecia areata (AA) is a common dermatological problem that manifests as sudden loss of hair without any inflammation or scarring. Various cytokines are implicated in the pathogenesis of this disease. Macrophage migration inhibitory factor (MIF) is located at an upstream position in the events leading to the possible dysregulated immuno-inflammatory responses, and the high level of this cytokine in AA may suggest a role of MIF in the pathogenesis of AA. MethodsThis case-control study was carried out on 31 AA patients with different grades of severity and 15 apparently healthy subjects. Serum MIF level was measured by ELISA, and was correlated with the clinical severity of the disease using SALT (severity of alopecia tool) scoring system.

The lowest dose of CLON injected into the

MnR decreased t

The lowest dose of CLON injected into the

MnR decreased the total risk assessment (TRA) frequency, an ethological parameter of anxiolytic-like effect, but did not change feeding behavior. The highest dose of CLON injected into the MnR increased the TRA frequency, an anxiogenic-like effect. Similar result was observed after CLON injected into the Pn and mRt at the highest dose. In addition, clonidine at the highest dose caused hyperphagy accompanied by a reduction in the latency to start eating and an increase in feeding frequency when injected into the MnR but not in the Pn or mRt. These data indicate that MnR alpha(2)-adrenergic receptors participate in the control of anxiety-like and feeding behaviors, probably decreasing the facilitatory influence on MnR serotonergic neurons. The present results click here suggest that

these behaviors involve independent neural pathways. (C) 2010 Elsevier B.V. All rights reserved.”
“Cold shock domain proteins (CSPs) are highly conserved from bacteria to higher plants and animals. Bacterial cold shock proteins function as RNA chaperones by destabilizing RNA secondary structures and promoting translation as an adaptative mechanism to low temperature stress. In animals, cold shock domain proteins exhibit broad functions related to growth and development. In order to understand better the function of CSPs in planta, detailed analyses were performed for 123 Arabidopsis selleck chemicals thaliana CSPs (AtCSPs) on the transcript and protein levels using an extensive series of tissue harvested throughout developmental stages within the entire life cycle of Arabidopsis. On both the transcript and protein levels, AtCSPs were enriched in shoot apical meristems and siliques. Although all AtCSPs exhibited similar expression patterns, AtCSP2 was the most abundantly expressed gene. In situ hybridization analyses were also used to confirm Panobinostat mouse that AtCSP2 and AtCSP4 transcripts accumulate in developing embryos and shoot apices. AtCSPs

transcripts were also induced during a controlled floral induction study. In vivo ChIP analysis confirmed that an embryo expressed MADS box transcription factor, AGL15, interacts within two AtCSP promoter regions and alters the respective patterns of AtCSP transcription. Comparative analysis of AtCSP gene expression between Landsberg and Columbia ecotypes confirmed a 1000-fold reduction of AtCSP4 gene expression in the Landsberg background. Analysis of the AtCSP4 genomic locus identified multiple polymorphisms in putative regulatory cis-elements between the two ecotypes. Collectively, these data support the hypothesis that AtCSPs are involved in the transition to flowering and silique development in Arabidopsis.”
“Background Despite early repair, patients with aortic coarctation (CoA) continue to have a reduced life expectancy due to the development of late complications.