Biochemical assays did not detect any evidence of cytotoxicity at

Biochemical assays did not detect any evidence of cytotoxicity at the concentrations used, apart from a concentration-related increase in cellular heme oxygenase that was also indicated by the genomic analysis. Cell signal pathway enrichment analysis indicated similar responses to both treatments, with concentration-related responses in pathways related to cell adhesion, cytoskeleton remodeling, development (morphogenesis), cell cycle control, and to a lesser extent inflammatory responses.

These cellular responses to arsenic were consistent PLX4032 with those observed in a previous study with primary uroepithelial cells. Benchmark dose analysis also demonstrated similar potency of the two treatments as well as comparable sensitivity of the two cell types. A number of genes C188-9 nmr showing similar concentration-dependent expression across individuals in both bladder and lung cells were identified, including heme oxygenase 1, thioredoxin reductase, DNA damage binding protein 2, and thrombomodulin. The data on human primary lung cells from this study, together with the data from

human primary uroepithelial cells, support a conclusion that biological responses to arsenic by human cells under study conditions are unlikely to occur at concentrations below 0.1 mu M. Environ. Mol. Mutagen. 56:477-490, 2015. (c) 2015 Wiley Periodicals, Inc.”
“The bacterial flagellar motor is a reversible rotary machine that rotates a left-handed helical filament, allowing bacteria to swim toward a more favorable environment. The direction of rotation reverses from counterclockwise (CCW) to clockwise (CW), and vice versa, in response to input from the chemotaxis signaling circuit. CW rotation is normally caused by binding of the phosphorylated response regulator CheY (CheY-P), and strains lacking CheY are typically locked in CCW rotation. The detailed mechanism of switching remains unresolved because it is technically difficult to regulate the level of CheY-P within the concentration range that produces flagellar reversals. Here, we demonstrate that high

hydrostatic pressure can induce CW rotation even in the-absence of CheY-P. Selleck PXD101 The rotation of single flagellar motors in Escherichia coil cells with the cheY gene deleted was monitored at various pressures-and-temperatures. Application of >120 MPa pressure induced a reversal from CCW to CW at 20 degrees C, although at that temperature, no motor rotated CW at ambient pressure (0.1 MPa). At lower temperatures, pressure-induced changes in direction were observed at pressures of <120 MPa. CW rotation increased with pressure in a sigmoidal fashion, as it does in response to increasing concentrations of CheY-P. Application of pressure generally promotes the formation of clusters of ordered water molecules on the surfaces of proteins. It is possible that hydration of the switch complex at high pressure induces structural changes similar to those caused by the binding of CheY-P.

(C) 2011

(C) 2011 www.selleckchem.com/products/AZD8931.html Elsevier BM. and Mitochondria Research Society. All rights reserved.”
“Background: Anemia is almost universal in trauma patients admitted to the intensive care unit (ICU). Hepcidin is a liver-derived peptide that is a negative regulator of iron stores. Hepcidin synthesis is suppressed by erythropoiesis and iron deficiency and upregulated by iron overload and inflammation. Hepcidin has been shown to have an important role in the anemia of chronic inflammatory diseases but has not been previously studied in the setting of trauma. We sought to define the link between traumatic injury, hepcidin, and inflammation.\n\nMethods: One hundred fifty trauma patients admitted to the ICU were

prospectively enrolled in the study. Urine was collected at regular time points for hepcidin measurement. Serum for iron studies and measurement of those cytokines associated with acute inflammation was also collected.\n\nResults: The study population comprised 73% men. Mean age was 46 years, with a median Injury Severity Score (ISS) of 27. The mean lactate level was 2.9 mmol/L, and mean hemoglobin was 12.4 g/dL. More than 50% of patients were anemic on ICU admission, and nearly all were anemic by postinjury day 10. Urinary hepcidin GS-7977 levels were among the highest

reported to date and had a rightward skew. Iron studies confirmed functional iron deficiency. Log hepcidin values were positively correlated with ISS and negatively correlated with admission PaO(2)/FiO(2). Every increase in ISS by

10 was associated with a 40% increase in hepcidin. Initial hepcidin levels were positively correlated with duration of anemia.\n\nConclusions: Hepcidin levels rise to extremely high but variable levels after trauma and are positively correlated with ML323 inhibitor injury severity measured by ISS and duration of anemia and negatively correlated with hypoxia. Hepcidin is likely a key factor in the impaired erythropoiesis seen in critically injured trauma patients.”
“Objectives: Bipolar patients frequently relapse within 12 months of their previous mood episode, even in the context of adequate treatment, suggesting that better continuation and maintenance treatments are needed. Based on recent research of the pathophysiology of bipolar disorder, we review the evidence for mitochondrial dysregulation and selected mitochondrial modulators (MM) as potential treatments.\n\nMethods: We reviewed the literature about mitochondrial dysfunction and potential MMs worthy of study that could improve the course of bipolar disorder, reduce subsyndromal symptoms, and prevent subsequent mood episodes.\n\nResults: MM treatment targets mitochondrial dysfunction, oxidative stress, altered brain energy metabolism and the dysregulation of multiple mitochondrial genes in patients with bipolar disorder.

Later, this pattern reversed Duration increased linearly for tho

Later, this pattern reversed. Duration increased linearly for those initially asked to suppress but was short and stable for those who initially monitored. Accounting for change over time and means of measuring recurrence (frequency

vs. duration) may help elucidate past mixed findings, and improve thought suppression research methodology. (C) 2013 Elsevier Ltd. All rights reserved.”
“In congenital Chuvash polycythemia (CP). VHLR200W homozygosity leads to elevated hypoxia inducible factor (HIF) levels at normoxia. CP is often treated by phlebotomy resulting in iron deficiency, permitting us to examine the separate and synergistic P505-15 datasheet effects of iron deficiency and HIF signaling on gene expression. We compared peripheral blood mononuclear cell gene expression profiles of eight VHLR200W homozygotes with 17 wildtype individuals with normal iron status and found 812 up-regulated and 2120 down-regulated genes at false discovery rate of 0.05. Among differential genes we identified LY294002 PI3K/Akt/mTOR inhibitor three major gene regulation modules involving induction of innate immune responses, alteration of carbohydrate and lipid metabolism, and down-regulation of cell proliferation, stress-induced

apoptosis and T-cell activation. These observations suggest molecular mechanisms for previous observations in CP of lower blood sugar without increased insulin and low oncogenic potential. Studies including 16 additional VHLR200W homozygotes with low ferritin indicated that iron deficiency enhanced the induction effect of VHLR200W for 50 genes including hemoglobin

synthesis loci but suppressed the effect for 107 genes enriched for HIF-2 targets. This pattern is consistent with potentiation of HIF-1 alpha protein stability by iron deficiency but a trend for down-regulation of HIF-2 alpha translation by iron deficiency overriding an increase in HIF-2 alpha protein stability. (C) 2013 Elsevier Inc. All rights reserved.”
“Background: Female cancer, especially breast and gynecologic cancers are considered multistage disease, highly influenced by risk and protective factors and/or screening preventive modalities. Consequences of all these factors result in the trend of change over time. Methods: learn more In this comparative study, based on data of national cancer registry of Iran 2004 published by Iranian Ministry of Health, age – standard incidence rate (ASR) according to the world population was calculated in all reported gynecologic and breast cancers. Source of all subjects are pathologic based. In the next step, the calculated ASR of Iran and those of the other countries in 2004 were compared to GLOBOCAN ASR reports of 2008. Results: In Iran ASR of breast cancer 2004 (24.93) changed to 18.4 in 2008. Ovarian cancer ASR of 2004, 3.07 was 3.1 in 2008. Endometrial cancer ASR in 2004 (2.29) was 1.7 in 2008. Cervical cancer ASR of 1.71 in 2004 was 2.2 in 2008. Conclusions: In Iran incidence trend of breast and endometrium are decreasing in the same direction of USA and Australia.

Treatment of MPE is moving toward less interventional approaches

Treatment of MPE is moving toward less interventional approaches that can manage patients in ambulatory settings thereby decreasing cost, discomfort, and time away from home for inpatient care.”
“This study was performed to determine isotherm and kinetic adsorption

of boron from synthetic wastewater using limestone as a low cost adsorbent. Boron adsorption was performed at optimum condition at pH range of 6-8, contact time of 90 min and limestone dosage of 240 g/L where the boron removal was achieved at 40%. Adsorption isotherm Selleck Nocodazole of boron on limestone was more representative by Freundlich model (R-2 = 0.91) rather than Langmuir model (R-2 = 78) indicated that multilayer adsorption was dominance. The kinetic study indicated that the adsorption of boron on limestone well obeyed pseudo-first order model (R-2 = 0.780), pseudo-second order (R-2 = 0.987), Elovich (R-2 = 0.931) and Intra-particle model (R-2 = 0.960). Chemically adsorption mechanisms were dominant in this study based on the highest R-2 for pseudo-second order model.”
“Most temperate woody plants have a winter chilling requirement to prevent budburst during midwinter periods of warm weather. The date of spring

budburst is dependent on both chilling and forcing; modeling this date is an important part of predicting potential effects of global warming on trees. There is no clear evidence from the literature that the CX-6258 curves of chilling or forcing effectiveness differ by species so we combined our data and published information to develop new curves on the effectiveness of temperature for chilling and forcing. The new curves predict effectiveness over a wide range of temperatures and we suggest both functions may be operating at the same time. We present experimental data from 13 winter environments for 5 genotypes of Douglas-fir (Pseudotsuga menziesii var. menziesii) and use them to test various assumptions of starting and stopping dates for accumulating chilling

and forcing units and the relationship between budburst and the accumulation of chilling and forcing units. Chilling started too early to be effective in one treatment but the other 12 environments resulted in budburst from many combinations of chilling and forcing. Previous reports have suggested benefits selleck compound or cancellations of effects from alternating day/night or periodic temperatures. Our simple models do not include these effects but nevertheless were effective in predicting relationships between chilling and forcing for treatments with a wide range of conditions. Overall, the date of budburst changed only slightly (+1 to -11 days) across a wide range of treatments in our colder test environment (Olympia, WA, USA) but was substantially later (+29 days) in the warmest treatment in our warmer environment (Corvallis, OR, USA).

Conclusion(s): This study describes for the first time that t

\n\nConclusion(s): This study describes for the first time that transferable quality blastocysts derived from infertile patients (male factor infertility and polycystic ovaries) possess aberrant miRNA profiles. With growing evidence indicating the importance of miRNAs during development, an association selleckchem may exist with human infertility. (Fertil Steril (R) 2010; 93: 2374-82. (C)2010 by American Society for Reproductive Medicine.)”
“The application of aqueous two-phase extraction for the downstream processing of lipase has been exploited. The influence of

system parameters such as phase forming salts, molecular weight of the phase forming polymer, system pH, tie line length, and phase volume ratio on the partitioning behavior of lipase was evaluated. The aqueous two-phase system consisting of PEG6000 and disodium

phosphate (Na(2)HPO(4)) resulted in one-sided partitioning of lipase with partition coefficient 0.11, activity recovery 116%, and purification factor of 2.25. Further, the purity of lipase was increased to 3.59-fold using multi-stage extractions.”
“In the past two far-view displays, which showed vital signs, trends, alarms, infusion pump status, and therapy support indicators, were developed and assessed by critical care nurses (Gorges et al. in Dimens Crit Care Nurs. 30(4):206-17, 2011). The aim of the current study is to assess the generalizability

of these findings to physicians. The first aim is to test whether an integrated far-view display, designed to be readable from 3 to 5 m, enables critical care buy VX-680 ARN-509 manufacturer physicians to more rapidly and accurately (1) recognize a change in patient condition; (2) identify alarms; and (3) identify near-empty infusion pumps, than a traditional patient monitor and infusion pump. A second aim is to test if the new displays reduce the mental workload required for this decision making. Fifteen critical care fellow physicians (median age of 34 years, with 2-8 years of ICU experience) were asked to use the three displays to compare the data from two patients and decide which patient required their attention first. Each physician made 60 decisions: 20 with each of the two far-view displays and 20 decisions with a standard patient monitor next to an infusion pump. A 41 and 26 % improvement in decision accuracy was observed with the bar and clock far-view displays, respectively. Specifically, the identification of near empty infusion pumps, a task normally performed by nurses, and patients with a single alarm were better with the new displays. Using the bar display physicians made their decision 12 % faster than when using the control display, a median improvement of 2.1 s. No significant differences were observed in measured workload.

I first developed an experimental system to analyze promoter acti

I first developed an experimental system to analyze promoter activity in primary cultured neuronal cells. Particularly focusing on the transcription regulation of the brain-derived neurotrophic factor (BDNF) gene (Bdnf), I found that the interaction of the cAMP response element-binding protein (CREB) with the CRE sequence is important for the activity-dependent activation of the Bdnf promoter. In addition, this activity-dependent transcriptional regulation occurs in cultured neurons stimulated with excitatory GABAergic inputs, which plays a critical role in promoting the step of neuronal differentiation. Finally, I found that stimulation of the G-protein coupled receptor (GPCR) Fer-1 inhibitor effectively

activates Bdnf promoter IV through selective activation of the calcineurin pathway, irrespective of the type of GPCR if the protein kinase A or C pathway is activated.

This induction mechanism appears important to understand intracellular mechanisms evoked via simultaneous GKT137831 Immunology & Inflammation inhibitor neurotransmission of excitatory and modulatory inputs into neurons of the brain.”
“Tian N, Moore RS, Phillips WE, Lin L, Braddy S, Pryor JS, Stockstill RL, Hughson MD, Manning RD Jr. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension. Am J Physiol Regul Integr Comp Physiol 295: R1858-R1865, 2008. First published October 15, 2008; doi:10.1152/ajpregu.90650.2008.-The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7- to 8-wk-old Dahl buy PCI-34051 salt-sensitive ( S) or R/Rapp strain rats were maintained for 5 wk on a high sodium ( 8%) or high sodium + apocynin ( 1.5 mmol/l in drinking water). Arterial and venous catheters were implanted on day 21. By day 35 in the high-Na S rats, mRNA expression of renal cortical gp91phox, p22phox, p47phox, and p67phox NADPH subunits in

S rats increased markedly, and treatment of high-Na S rats with the NADPH oxidase inhibitor apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time, in apocynin-treated S rats 1) renal cortical GSH/GSSG ratio increased, 2) renal cortical O(2)(center dot-) release and NADPH oxidase activity decreased, and 3) renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/ macrophage infiltration, and apocynin, but not the xanthine oxidase inhibitor allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation, which lead to decreases in renal hemodynamics, renal cortical damage, and increases in arterial pressure.

A46 binds to MyD88, Mal/TIRAP, TRIF and TRAM and suppresses the a

A46 binds to MyD88, Mal/TIRAP, TRIF and TRAM and suppresses the activation of NF-kappa B and interferon regulatory factors. Each of these cytosolic adaptors Selleck PLX3397 has a TIR domain that is critical for oligomerization during signaling. Although the structure of A46 is unknown, it has alternatively been described as an alpha/beta-fold TIR domain, or an all alpha-helical Bcl-2 fold. Here we provide experimental evidence that the C-terminus of A46 adopts a dimeric alpha-helical structure, and that this segment retains the ability to interact with monomeric Mal. Furthermore, a peptide fragment

of A46 termed VIPER, previously shown to retain the biological properties of the full-length protein, does not interact with Mal in vitro. In summary, we provide for the first time a biophysical analysis of the binding of a poxvirus protein to a TIR domain-containing Selleck Selisistat adaptor molecule. (C) 2011 Elsevier Ltd. All rights reserved.”
“This study aimed to identify the optimal neural progenitor cell transplantation time for spinal cord injury in rats via the subarachnoid space. Cultured neural progenitor cells from 14-day embryonic rats, constitutively expressing enhanced green fluorescence protein, or media alone, were injected into the subarachnoid space of adult rats at 1 hour (acute stage),

7 days (subacute stage) and 28 days (chronic stage) after contusive spinal cord injury. Results showed that grafted neural progenitor cells migrated and aggregated around the blood vessels of the injured region, and infiltrated the spinal cord parenchyma along the tissue spaces in the acute stage transplantation group. However, this was not observed

in subacute and chronic stage transplantation groups. O4- and glial fibrillary acidic protein-positive cells, representing oligodendrocytes and astrocytes respectively, were detected in the core of the grafted cluster attached to the cauda equina pia surface in the chronic stage transplantation group 8 weeks after transplantation. Both acute and subacute stage transplantation groups were negative for O4 and glial fibrillary acidic protein cells. Basso, Beattie and Bresnahan scale score comparisons indicated that rat hind limb locomotor activity showed better recovery after acute stage selleck transplantation than after subacute and chronic transplantation. Our experimental findings suggest that the subarachnoid route could be useful for transplantation of neural progenitor cells at the acute stage of spinal cord injury. Although grafted cells survived only for a short time and did not differentiate into astrocytes or neurons, they were able to reach the parenchyma of the injured spinal cord and improve neurological function in rats. Transplantation efficacy was enhanced at the acute stage in comparison with subacute and chronic stages.

To determine if brief interventions could be used successfully by

To determine if brief interventions could be used successfully by nurses in the clinical setting.\n\nBackground.\n\nAustralian adolescents are consuming risky levels of alcohol in ever increasing numbers. The fiscal, health-related and social costs of this alcohol misuse are rising at an alarming rate and must be addressed as a matter of priority. Brief interventions have been used with some success for adult SNX-5422 datasheet problem drinkers in the clinical setting. Brief interventions delivered in the clinical setting by nurses who are ‘on the scene’ are therefore a potential strategy to redress the epidemic of adolescent

alcohol misuse.\n\nDesign.\n\nLiterature review.\n\nMethods.\n\nMultiple databases were searched to locate randomised controlled trials published within the past 10 years, with participants

aged 12-25 years. Included studies used brief intervention strategies specific to alcohol reduction. Fourteen studies met these criteria and were reviewed.\n\nResults.\n\nA range of check details different interventions, settings, participant age-ranges and outcome measures were used, limiting generalisability to the studied populations. No trials were carried out by nurses and only one took place in Australia. Motivational interviewing (one form of brief intervention) was partially successful, with the most encouraging results relating to harm minimisation. Long-term follow-up trials using motivational interviewing reported significant reductions in alcohol intake and harmful effects, but this may be partially attributed to a normal maturation trend to a steady reduction in alcohol consumption.\n\nConclusions.\n\nNo single intervention could be confidently recommended due to confounding evidence. However, successful elements of past studies warrant further investigation. These include face-to-face, one-session, motivational interviewing-style brief interventions, focusing on harm minimisation and all with long-term follow-up.\n\nRelevance

to clinical practice.\n\nThe introduction of brief interventions in the hospital setting has the potential to address the epidemic of adolescent alcohol misuse. Nurses are well placed to deliver BI-6727 these interventions, but a standardised approach is required to ensure consistency. Further research is urgently needed to ensure clinical practice is based on the best available evidence and to ensure findings are more relevant to Australian adolescents and to nurses in a clinical setting.”
“In this article is evaluating the relationship between the level of creativity and variables which affect unemployment such as age, gender and period of unemployment. The creativity were explored using a sample consisted on 140 unemployed people. The results derived by application of different statistical analysis, using quantitative methodology of descriptive character, indicated that the studied mediating variables do not show any significant incidence in the creativity of people unemployed.

(C) 2013 Elsevier GmbH All rights reserved “
“This paper is

(C) 2013 Elsevier GmbH. All rights reserved.”
“This paper is devoted to the equilibrium shapes of rotating liquid drops. Families of axisymmetric shapes are found using a perturbation technique for the governing nonlinear equation. Bifurcation and turning points are located by applying a special type of Hermite-Pade approximation. (C) 2013 Elsevier Inc. All rights reserved.”
“BACKGROUND:

Disparities in healthcare for the elderly are understudied, despite the increasing proportion of patients over 80 years of age. Advanced age is a principal risk factor for colorectal adenocarcinoma, but there are few data to guide treatment in the elderly patient population.\n\nMETHODS: We performed a retrospective review of prospectively gathered data on 10,433 patients diagnosed with primary colon tumors between 1998 and 2004. We compared demographics, stage at diagnosis, and initial treatment between Selleckchem Captisol patients Younger than 80 years and

those age 80 years or older.\n\nRESULTS: Patients who were >= 80 years old find more made up 30% of the database. Older patients were less likely to have colectomy for advanced or metastatic disease than younger patients. Patients who were >= 80 years of age had fewer lymph nodes removed than younger patients (11 vs 10, P <.01). Older patients were significantly less likely to receive chemotherapy for every stage of colon cancer than younger patients. When older patients did get chemotherapy, it was more likely to be with a single agent. Multivariate analysis revealed that predictors of receiving chemotherapy for patients >= 80 years of age include living in an urban county, younger age, and worse stage at diagnosis.\n\nCONCLUSIONS: Older patients make up a large portion of the patients treated for colon cancer

and are treated less aggressively. While some of the treatment difference may be explained by medical factors, demographic factors affect treatment decisions as well. (C) 2009 Elsevier Inc. All rights reserved.”
“In pregnant rats, a significant decrease in myometrial relaxin family peptide receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for activation of myometrial contractions, occurs in late gestation and during spontaneous labor. This coincides with BIIB057 molecular weight the highest level of circulating relaxin and a decrease in progesterone. We investigated the potential regulatory role of these two systemic factors on myometrial RXFP1 expression by examining the effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin (MCA1) in pregnant rats. Rats were injected with RU486 on Gestational Day (GD) 7, 16, or 19 and were killed on GD 8, 17, or 20. RU486 caused a significant reduction in myometrial RXFP1. Plasma progesterone and 17beta-estradiol levels were increased in RU486-treated animals compared with controls.

(C) 2012 Elsevier B V All rights reserved “
“Vertebrates ha

(C) 2012 Elsevier B.V. All rights reserved.”
“Vertebrates have succeeded to inhabit almost every ecological niche due in large part to the anatomical diversification of their jaw complex. As a component of the feeding apparatus, jaw muscles carry a vital role for determining the mode of feeding. Early patterning of Saracatinib Angiogenesis inhibitor the jaw muscles has been attributed to cranial neural crest-derived mesenchyme, however, much remains to be understood about the role of nonneural crest tissues in the evolution and diversification of jaw muscle morphology. In this study, we describe the development of trigeminal motor neurons in a parrot species with the uniquely shaped jaw muscles and compare its developmental pattern to that

in the quail with the standard jaw muscles to uncover potential roles of nervous tissue in the evolution of vertebrate jaw muscles. In parrot embryogenesis, the motor axon bundles are detectable within the muscular tissue

LY2606368 only after the basic shape of the muscular tissue has been established. This supports the view that nervous tissue does not primarily determine the spatial pattern of jaw muscles. In contrast, the trigeminal motor nucleus, which is composed of somata of neurons that innervate major jaw muscles, of parrot is more developed compared to quail, even in embryonic stage where no remarkable interspecific difference in both jaw muscle morphology and motor nerve branching pattern is recognized. Our data suggest that although nervous tissue may not have a large influence on initial patterning of jaw muscles, it may play an important role in subsequent growth and

maintenance of muscular tissue and alterations in cranial nervous tissue development may underlie diversification of jaw muscle morphology. J. Morphol. 275:191-205, 2014. (c) 2013 Wiley Periodicals, Inc.”
“Using the perturbation approach, we have calculated the donor impurity related photoionization cross-section in a quantum dot under different temperature and hydrostatic pressure conditions. Our calculation have revealed the dependence of the photoionization cross-section on the confinement strength, ASP2215 research buy temperature and hydrostatic pressure. (C) 2011 Elsevier Ltd. All rights reserved.”
“The primary aim of the present study was to assess the gray scale intravascular ultrasound (IVUS) findings that might be associated with late drug-eluting stent restenosis. The study included 47 patients (54 lesions) who had undergone either baseline IVUS-guided stent implantation or IVUS-guided repeat stenting to treat in-stent restenosis and then had IVUS follow-up data for >= 1.5 years afterward without any intervening procedures. The left anterior descending artery was the culprit in 59% of cases, and 50% of the lesions were at bifurcation sites. Quantitative and qualitative IVUS analyses showed a decreased minimum lumen area at follow-up from 6.0 +/- 1.8 to 3.8 +/- 1.