The objective of this systematic review is to evaluate the benefi

The objective of this systematic review is to evaluate the benefits

and harms of available interventions for HUS and TTP.\n\nSelection Criteria for Studies: MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), the Cochrane Central Register, conference proceedings, and reference lists were searched to find randomized controlled trials (RCTs) of any intervention for HUS or TTP in patients of all ages selected for inclusion for this systematic review.\n\nInterventions: Trials that compared an intervention with placebo, an intervention with supportive therapy, or one or more different interventions for HUS or TTP.\n\nOutcomes: For TTP trials, failure of remission at 2 weeks or less and at 1 month or longer, all-cause mortality rate, and relapse rate. For HUS trials, all-cause mortality, chronic reduced kidney function, and persistent AZD3965 proteinuria or hypertension

at last follow-up.\n\nResults: For TTP in adults, we found 6 RCTs of 331 patients. Two trials compared plasma infusion selleck chemical with plasma exchange using fresh frozen plasma and showed failure of remission at 2 weeks (2 trials, 140 patients; relative risk, 2.87; 95% confidence interval, 1.41 to 5.84), and all-cause mortality (relative risk, 1.91; 95% confidence interval, 1.09 to 3.33) occurred more frequently in the plasma infusion group. Three trials compared plasma exchange using cryosupernatant plasma with plasma exchange using fresh frozen plasma, and a meta-analysis of these trials showed no difference. Seven RCTs in 476 young children with postdiarrheal HUS have been conducted. None of the evaluated interventions (fresh frozen plasma transfusion, heparin with or without urokinase or dipyridamole, Shiga toxin-binding

protein, and steroid) were superior to supportive therapy alone for any outcomes.\n\nLimitations: Limitations of this review include the small number and suboptimal quality of reporting of included trials, possibility of publication bias, small number of participants with atypical HUS, and failure to report results for patients with atypical and typical HUS separately.\n\nConclusions: No additional Thiazovivin datasheet therapy has been shown to increase efficacy over plasma exchange for TTP. No intervention has been shown to be superior to supportive therapy in patients with postdiarrheal HUS.”
“Rief and Hofmann (2009, Nervenarzt 80: 593597) harshly criticise the meta-analysis on the effectiveness of long-term psychodynamic psychotherapy (LTPP) by Leichsenring and Rabung (2008, JAMA 300(13):1551-1565). They find fault with the inclusion of naturalistic studies in addition to randomised clinical trials. Furthermore, they criticise the heterogeneity of the treatments included and the disorders studied. They suspect that a number of RCTs of LTPP with negative results for LTPP have been done and not been published.

Although, in theory, BCTs can amplify each other,

Although, in theory, BCTs can amplify each other, LGX818 the available meta-analyses have not been able to identify specific combinations of techniques that provide synergistic effects. This study overcomes some of the shortcomings in the current methodology by applying classification and regression trees (CART) to meta-analytic data in a special way, referred to as Meta-CART. The aim was to identify particular combinations of BCTs that explain

intervention success. Method: A reanalysis of data from Michie, Abraham, Whittington, McAteer, and Gupta (2009) was performed. These data included effect sizes from 122 interventions targeted at physical activity and healthy eating, and the coding of the interventions into 26 BCTs. A CART analysis

was performed using the BCTs as predictors and treatment success (i.e., effect size) as outcome. A subgroup meta-analysis using a mixed effects model was performed AZD0530 price to compare the treatment effect in the subgroups found by CART. Results: Meta-CART identified the following most effective combinations: Provide information about behavior-health link with Prompt intention formation (mean effect size (g) over bar = 0.46), and Provide information about behavior-health link with Provide information on consequences and Use of follow-up prompts ((g) over bar = 0.44). Least effective interventions were those using Provide feedback on performance without using Provide instruction ((g) over bar = 0.05). Conclusions: Specific combinations of BCTs increase the likelihood of achieving change in health behavior, whereas other combinations decrease this likelihood. Meta-CART successfully identified these combinations and thus provides a viable methodology in the context of meta-analysis.”
“Epidemiological studies have correlated arsenic exposure

with cancer, skin diseases, and adverse developmental outcomes such as spontaneous abortions, neonatal mortality, low birth weight, and delays in the use of musculature. www.selleckchem.com/products/stattic.html The current study used C2C12 mouse myoblast cells to examine whether low concentrations of arsenic could alter their differentiation into myotubes, indicating that arsenic can act as a developmental toxicant. Myoblast cells were exposed to 20 nM sodium arsenite, allowed to differentiate into myotubes, and expression of the muscle-specific transcription factor myogenin, along with the expression of tropomyosin, suppressor of cytokine signaling 3 (Socs3), prostaglandin 12 synthesis (Ptgis), and myocyte enhancer 2 (Mef2), was investigated using QPCR and immunofluorescence. Exposing C2C12 cells to 20 nM sodium arsenite delayed the differentiation process, as evidenced by a significant reduction in the number of multinucleated myotubes, a decrease in myogenin mRNA expression, and a decrease in the total number of nuclei expressing myogenin protein. The expression of mRNA involved in myotube formation, such as Ptgis and Mef2 mRNA, was also significantly reduced by 1.

(C) 2010 Elsevier Ltd All rights reserved “
“In an effort t

(C) 2010 Elsevier Ltd. All rights reserved.”
“In an effort to improve the stability of labile lactone ring and water solubility of camptothecin, five novel spin-labeled camptothecin derivatives were synthesized in quantitative

yield by a simple modification of the carbodiimide method using the combination of scandium triflate (Sc(OTf)(3)) and 4-dimethylaminopyridine (DMAP), and the in vitro pharmacokinetic determination of the lactones of representative compound 13a showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compound camptothecin. Also, the in vitro cytotoxicity of compounds 13a-13e against human bladder cancer T-24 showed either similar or better activity than that of the parent drug, camptothecin, and clinically available drug, irinotecan. NU7441 molecular weight (C) 2008 Elsevier

Masson SAS. All rights reserved.”
“Context. Religious coping is important for end-of-life treatment preferences, advance care planning, adjustment to stress, and quality of life. The currently AZD9291 in vitro available religious coping instruments draw on a religious and spiritual background that presupposes a very specific image of God, namely God as someone who personally interacts with people. However, according to empirical research, people may have various images of God that may or may not exist simultaneously. It is unknown whether one’s belief in a specific image of God is related to the way one copes with

a life-threatening disease.\n\nObjectives. To examine the relation between adherence to a. personal, a nonpersonal, and/or an unknowable image of God and coping Selleck NCT-501 strategies in a group of Dutch palliative cancer patients who were no longer receiving antitumor treatments.\n\nMethods. In total, 68 palliative care patients completed and returned the questionnaires on Images of God and the COPE-Easy.\n\nResults. In the regression analysis, a nonpersonal image of God was a significant positive predictor for the coping strategies seeking advice and information (beta = 0.339, P < 0.01), seeking moral support (beta = 0.262, P < 0.05), and denial (beta = 0.26, P < 0.05), and a negative predictor for the coping strategy humor (beta = -0.483, P < 0.01). A personal image of God was a significant positive predictor for the coping strategy turning to religion (beta = 0.608, P < 0.01). Age was the most important sociodemographic predictor for coping and had negative predictive value for seeking advice and information (beta = -0.268, P < 0.05) and seeking moral support (beta = -0.247, P < 0.05).\n\nConclusion.


“Is complexity growth the result of a continuous process o


“Is complexity growth the result of a continuous process or a sudden breakthrough? An increased energy density rate is the effect or the cause of a complexity leap? Should we approach complexity change by the perspective of components

behaviour or system’s space geometry? In this work we address some of the questions regarding the theoretical approach to complexity selleck kinase inhibitor change. For this purpose a case study drawn by the productive structure and the transport system is considered. We would like here to propose an example in which the system structure is reshaped in a more energy intensive fashion as to increase the components’ interactions due to a symmetry rupture in the space. Flows throughout the system are thereby incremented in a discontinuous way by a complexity leap. In the case study, we analyze how the productive system evolved its structure, between 1970s and 1990s, to increase interactions among its parts and thus further develop the transport sub-system. A two-stage shift has been considered:

the fordian and the post-fordian productive structure. The second structure, given the same amount of parts, has been shown to increase the degree of freedom (path AZD8931 order length and path diversity) of the system. The underlying evolutionary pattern is then analyzed. This evolutionary pattern relies on the hypothesis that thermodynamic evolutionary systems are characterized by an ever growing influx of energy driven into the system by self-catalytic processes that must find their way through the constraints of the system. The system initially disposes of the energy by expanding, in extent and in the number of components, up to saturation due to inner or outer constraints. The two counteractive forces, constraints and growing energy flux, expose the system to new gradients. Every new (spatial) gradient upon the system

represents a symmetry rupture in the components’ space. By exploring a new gradient, the system imposes further restrictions on its components and increases its overall degree of freedom. The counteractive effects of reduction/increase of degree Ricolinostat price of freedom concern two different hierarchical levels and occur at two different space and time scales. (C) 2009 Elsevier B.V. All rights reserved.”
“Aims: Cisplatin (CDDP) is a platinum-based drug that is widely used in cancer chemotherapy, but the development of resistance in tumor cells is a major weakness of these treatments. Several mechanisms have been proposed to explain cisplatin resistance, and disruption of certain cellular pathways could modulate drug sensitivity to cisplatin. A lower level of cross-resistance to cisplatin leads to better outcomes in clinical use. Main methods: Cross-resistance was assessed using cisplatin resistant lung cancer cell line A549/CDDP.

Materials and Methods: In vitro investigation of angiogenesis

\n\nMaterials and Methods: In vitro investigation of angiogenesis was conducted utilizing HUVEC cells in Matrigel. Endothelial tubule formation assays were divided into four groups: Control, Radiated, Radiated + Low-Dose TH-302 DFO and Radiated + High-Dose DFO. Tubule formation was quantified microscopically and video recorded for the four groups simultaneously during the experiment.

In vivo, three groups of Sprague-Dawley rats underwent external fixator placement and fracture osteotomy of the left mandible. Two groups received pre-operative fractionated radiotherapy, and one of these groups was treated with DFO after fracture repair. After 40 days, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics.\n\nResults: In vitro, endothelial Selleck 3-deazaneplanocin A tubule formation assays demonstrated that DFO mitigated the deleterious effects of radiation on angiogenesis. Further, high-dose DFO cultures appeared to organize within 2 h of incubation and achieved a robust network that was visibly superior to all other experimental groups in an accelerated fashion. In vivo, animals subjected to a human equivalent dose of radiotherapy (HEDR) and left mandibular fracture demonstrated quantifiably diminished mu CT metrics of vascular density, as well as a 75% incidence of associated non-unions. The addition of

DFO in this setting markedly improved selleck screening library vascularity as demonstrated with 3D angiographic modeling. In addition, we observed an increased incidence of bony unions in the DFO treated group when compared to radiated fractures without treatment (67% vs. 25% respectively).\n\nConclusion: Our data suggest that selectively targeting angiogenesis with localized DFO injections is sufficient to remediate the associated severe vascular diminution resulting from a HEDR. Perhaps the most consequential and clinically relevant finding was the ability to reduce the incidence of non-unions in a model

where fracture healing was not routinely observed. (C) 2012 Elsevier Inc. All rights reserved.”
“We recently identified LY2033298 as a novel allosteric potentiator of acetylcholine (ACh) at the M-4 muscarinic acetylcholine receptor (mAChR). This study characterized the molecular mode of action of this modulator in both recombinant and native systems. Radioligand-binding studies revealed that LY2033298 displayed a preference for the active state of the M-4 mAChR, manifested as a potentiation in the binding affinity of ACh (but not antagonists) and an increase in the proportion of high-affinity agonist-receptor complexes. This property accounted for the robust allosteric agonism displayed by the modulator in recombinant cells in assays of [S-35]GTP gamma S binding, extracellular regulated kinase 1/2 phosphorylation, glycogen synthase kinase 3 beta phosphorylation, and receptor internalization.

These data suggested that AGTRL1 did not contribute much to the a

These data suggested that AGTRL1 did not contribute much to the atherosclerosis of the coronary artery. Journal of Human Genetics (2009) 54, 554-556; doi:10.1038/jhg.2009.78; published online 14 August 2009″
“hPEBP4 (human phosphatidylethanolamine-binding protein 4) has been identified to be able to potentiate the resistance of breast, prostate, and ovarian cancers, with the preferential expression of hPEBP4, to

tumor necrosis factor-alpha Trichostatin A manufacturer (TNF-alpha) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, suggesting that inhibitors targeting the anti-apoptotic protein hPEBP4 may be useful to increase the sensitivity of hPEBP4-expressing cancer cells to TNF-alpha or TRAIL-induced apoptosis. By structure-based virtual screening and following surface plasmon resonance-based binding assay, seven small

compounds were found to potently bind with hPEBP4. The hit compounds were further functionally screened for their ability to inhibit cancer cell growth, and one small compound, IOI-42, find more was identified to be able to promote TNF-alpha-mediated growth inhibition of MCF-7 breast cancer cells. IOI-42 could potentiate TNF-alpha-induced apoptosis of MCF-7 cells by inhibiting hPEBP4 and could suppress anchorage-independent cell growth of MCF-7 cells. We further demonstrated that IOI-42 could reduce the endogenous association of hPEBP4 with Raf-1/MEK1 and enhance the activation of ERK1/2 and JNK while inhibiting Akt activation. Furthermore, IOI-42 also promoted TRAIL-induced cell apoptosis of prostate cancer cells. Taken together, our data suggest that IOI-42, as the first chemical inhibitor of anti-apoptotic protein hPEBP4, may serve as a potential anti-tumor drug by sensitizing tumor cells to apoptotic inducers.”
“Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases,

which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ataxin-3. Ataxin-3 selleck is mainly localized in the cytoplasm: however, one hallmark of SCA3 is the formation of ataxin-3-containing protein aggregates in the nucleus of neurons. Currently, it is not known how mutant ataxin-3 translocates into the nucleus.\n\nWe performed localization assays of recently proposed and novel potential signals, functionally confirmed the activity of a nuclear localization signal, identified two novel nuclear export signals (NES 77 and NES 141), and determined crucial amino acids. In addition, we demonstrate the relevance of the identified signals for the intracellular localization of the N- and C-terminus of ataxin-3. Our findings stress the importance of investigating the mechanisms, which influence the intracellular distribution of ataxin-3 during the pathogenesis of SCA3. (C) 2009 Elsevier Inc. All rights reserved.

The addition of Mg-GTP to MobA loaded with bis-Mo-MPT resulted in

The addition of Mg-GTP to MobA loaded with bis-Mo-MPT resulted in formation and release of the final bis-MGD product.

This cofactor was fully functional and reconstituted the catalytic activity of apo-TMAO reductase (TorA). We propose a reaction sequence for bis-MGD formation, which involves 1) the formation of bis-Mo-MPT, 2) the addition of two GMP units to form bis-MGD on MobA, and 3) the release and transfer Apoptosis Compound Library solubility dmso of the mature cofactor to the target protein TorA, in a reaction that is supported by the specific chaperone TorD, resulting in an active molybdoenzyme.”
“To better understand how elevated androgen levels regulate food intake and obesity in females, we treated ovariectomized female mice with dihydrotestosterone (DHT) (non-aromatazable androgen), measured food intake and body weight, and evaluated physiological changes in liver function, glucose tolerance, and leptin resistance. DZNeP datasheet Ovariectomized mice were treated with DHT or placebo. Mice were then fed a high fat diet under free-feeding or pair-feeding conditions for 3 months. We found that when DHT-treated ovariectomized mice had free access to food (free-feeding), they had increased food intake and higher body weight compared with control animals. These mice also had a significantly greater accumulation of fat in the liver and exhibited increased fasting glucose, impaired glucose tolerance,

and resistance to leptin. However, when these

mice were placed on a restricted diet and fed the same caloric amounts as controls (pair-feeding), their body weight increased at the same rate as control animals. This suggests that androgen regulates food intake through altered leptin sensitivity, and this increase of food intake could significantly contribute to an obesity phenotype. In summary, we demonstrated a role for androgen in the regulation of food intake and weight gain in females using a mouse model. This model will be useful Entinostat to further elucidate the role of elevated androgen in females. (C) 2013 Elsevier Ltd. All rights reserved.”
“Gold nanorods (GNRs), which strongly absorb near-infrared (NIR) light, have shown great potential in fields of biomedical application. These include photothermal therapy, molecular imaging, biosensing, and gene delivery, especially for the treatment of diseased tissues such as cancer. These biomedical applications of GNRs arise from their various useful properties; photothermal (nanoheater) properties, efficient large scale synthesis, easy functionalization, and colloidal stability. In addition, GNRs do not decompose and have an enhanced scattering signal and tunable longitudinal plasmon absorption which allow them to be used as a stable contrast agent. Therefore, GNRs are also promising theranostic agents, combining both tumor diagnosis and treatment.

43%) had colorectal cancer during the 5-year follow-up period: 15

43%) had colorectal cancer during the 5-year follow-up period: 15 (5.45% of those with cryptogenic PLA) and 25 from the comparison group (1.82% of the comparison group). After adjusting for patients’ age, sex, monthly income, level of urbanization and geographical location, the hazard of colorectal cancer during the 5-year period was 3.36 times greater for patients

with cryptogenic PLA than for the comparison group [95% confidence interval (CI) = 1.72-6.56, P < 0.001]. The adjusted hazard of colorectal cancer during the 5-year follow-up period was 5.54 times higher for cryptogetic PLA patients with diabetes GW786034 in vivo (95% CI = 2.11-14.56, P < 0.001) than the comparison group and 2.64 times higher among PLA patients without diabetes (95% CI = 1.19-5.85, P < 0.05). Conclusions: We conclude that cryptogenic PLA is an alarm that may signal colorectal cancer, especially among female patients with diabetes.”
“Women with congenital adrenal hyperplasia

(CAH) caused by steroid 21-hydroxylase deficiency show reduced fertility, especially with the salt-wasting form. A 27-year-old pregnant woman with this disease PLX4032 underwent laparotomy and oophorectomy to remove a multilocular ovarian tumor at 14 weeks of pregnancy. This proved to be a mucinous cystadenoma. Toward the third trimester, she presented with marked elevations of 17 alpha-hydroxyprogesterone and plasma renin activity. Careful management of endocrine and body fluid homeostasis allowed her to give birth to a healthy female infant with normal external genitalia. This case illustrates endocrinological parameters during pregnancy in a woman with classical salt-wasting CAH.”
“Combined lesser scaup (Aythya affinis) and greater scaup ( A. marila) populations have declined steadily from the 1970s. Accompanying the population

decline have been two shifts in lesser scaup demographics: a decrease in the proportion of young birds and an increase in male to female ratio. In addition, there are concerns about potential effects of contaminants and trace elements. These metals may influence the stress response Vorinostat ic50 and corticosterone secretion. We examined impacts of cadmium, selenium and mercury on the stress response in relation to social status in male lesser scaup near Yellowknife, NWT May to June 2004 and 2005. Kidney cadmium and liver selenium and mercury ranged 0.78-93.6, 2.12-9.64, and 0.56-3.71 mu g/g, dry weight, respectively. Results suggest that corticosterone release may be influenced by complex contaminant interactions in relation to body condition and body size. When cadmium was high and birds were in good body condition, there was a negative relationship between liver selenium and corticosterone (R-2 = 0.60, n = 10, P = 0.008) but not in birds with poor body condition (R-2 = 0.07, n = 9, P = 0.50). Unfortunately we were unable to draw any conclusions about metals and social status in relation to corticosterone or glucose and T-4.

The RAI-MH includes a breadth of information on symptoms, functio

The RAI-MH includes a breadth of information on symptoms, functioning, socio-demographics, and service utilization. Potential MHQIs were derived by examining the empirical patterns of improvement and incidence in depressive symptoms and cognitive performance across facilities in both sets of data. A prevalence indicator was also constructed to compare restraint use. Logistic regression was used to evaluate risk adjustment of MHQIs using patient case-mix index scores derived from the RAI-MH System

for Classification of Inpatient Psychiatry.\n\nResults: Subscales from the RAI-MH, the Depression Severity Index (DSI) and this website Cognitive Performance Scale (CPS), were found to have good reliability and strong convergent validity. Unadjusted rates of five MHQIs based on the DSI, CPS, and restraints

showed substantial variation among facilities in both sets of data. For instance, there was a 29.3% difference between the first and third quartile facility rates of improvement in cognitive performance. The case-mix index score was significantly related to MHQIs for cognitive performance and restraints but CX-6258 chemical structure had a relatively small impact on adjusted rates/prevalence.\n\nConclusions: The RAI-MH is a feasible assessment system for deriving MHQIs. Given the breadth of clinical content on the RAI-MH there is an opportunity to expand the number of MHQIs beyond indicators of depression, cognitive performance, click here and restraints. Further research is needed to improve risk adjustment of the MHQIs for their use in mental health services report card and benchmarking activities.”
“Pectins are complex polysaccharides that are essential components of the plant cell wall. In this study, a novel putative Arabidopsis

S-adenosyl-L-methionine (SAM)-dependent methyltransferase, termed QUASIMODO 3 (QUA3, At4g00740), has been characterized and it was demonstrated that it is a Golgi-localized, type II integral membrane protein that functions in methylesterification of the pectin homogalacturonan (HG). Although transgenic Arabidopsis seedlings with overexpression, or knock-down, of QUA3 do not show altered phenotypes or changes in pectin methylation, this enzyme is highly expressed and abundant in Arabidopsis suspension-cultured cells. In contrast, in cells subjected to QUA3 RNA interference (RNAi) knock-down there is less pectin methylation as well as altered composition and assembly of cell wall polysaccharides. Taken together, these observations point to a Golgi-localized QUA3 playing an essential role in controlling pectin methylation and cell wall biosynthesis in Arabidopsis suspension cell cultures.”
“Introduction: The face is the central point of the physical features; it transmits expressions and emotions, communicates feelings and allows for individual identity.

On the other hand, TIMP1 was expressed more often in decidual

On the other hand, TIMP1 was expressed more often in decidual

cells than in cancer stromal cells. Immunostaining for TIMP2 was more extensive and intense both in trophoblastic and decidual cells than in cancer parenchymal and stromal cells, respectively. The reduced expression of TIMP2 in metastatic carcinomas by comparison with non-metastatic gestation specimens underlines its importance in cancer invasion and migration. On the other hand, TIMP1 was more expressed in decidua than cancer stroma, but at the same time showed no statistically significant difference between cancer parenchyma and trophoblasts, highlighting its multifunctional activity in cancer Crenigacestat progression.”
“Bacterial sialidases are a group of glycohydrolases that are known to play an important role in invasion of host cells and tissues. In this study, we examined in a model of Japanese flounder (Paralichthys olivaceus) the potential function of NanA, a sialidase from

selleck chemicals the fish pathogen Edwardsiella tarda. NanA is composed of 670 residues and shares low sequence identities with known bacterial sialidases. In silico analysis indicated that NanA possesses a sialidase domain and an autotransporter domain, the former containing five Asp-boxes, a RIP motif, and the conserved catalytic site of bacterial sialidases. Purified recombinant NanA (rNanA) corresponding to the sialidase domain exhibited glycohydrolase activity against sialic acid substrate in a manner that is pH and temperature dependent. Immunofluorescence microscopy showed binding of anti-rNanA antibodies to E. tarda, suggesting that NanA was localized on cell surface. Mutation of nanA caused drastic attenuation in the ability of E. tarda to disseminate into and colonize fish tissues and to induce mortality in infected fish. Likewise, cellular study showed that the nanA mutant was significantly impaired in the infectivity against cultured flounder cells. Immunoprotective analysis showed that rNanA in the form of a subunit vaccine conferred effective protection upon flounder against lethal E. tarda

challenge. rNanA vaccination induced the production LY3039478 concentration of specific serum antibodies, which enhanced complement-mediated bactericidal activity and reduced infection of E. tarda into flounder cells. Together these results indicate that NanA plays an important role in the pathogenesis of E tarda and may be exploited for the control of E. tarda infection in aquaculture. (C) 2012 Elsevier Ltd. All rights reserved.”
“The objective of this study was to evaluate the effect of wax concentration (0.5 and 1%), cooling rate (0.1, 1, and 10 degrees C/min), and high-intensity ultrasound (HIU) on the crystallization behavior of beeswax (BW) in six different edible oils. Samples were crystallized at 25 degrees C with and without HIU.