“The idea that diversity begets the functioning and stabil


“The idea that diversity begets the functioning and stability of ecosystems has been intensely examined in terrestrial habitats, yet these relationships remain poorly studied in the marine realm. Theoretical and empirical work suggest that diversity enhances the stability of communities, but decreases the stability of populations. This is because compensatory dynamics, such as when one species decreases while another increases, stabilise the community as long as species richness increases the variety of responses to the environment. In an observational field study, the temporal variability in species abundance was used as a measure of stability that was compared among 5 intertidal

sites of naturally different species richness. Percent coverage of macrobenthic species was estimated every 6 mo for 2 yr. Stability Selleck RepSox in total community coverage was a negative but curvilinear function of species richness. In addition, the stability of single populations (averaged

over all species) fluctuated across the species richness gradient, without showing the predicted negative pattern. CCI-779 molecular weight We found no evidence for increasing compensatory dynamics with increasing species richness, suggesting that the variety of responses to environmental changes was unrelated to diversity. Diversity-stability relationships in natural communities may be more complex than those predicted by theory and manipulative experiments.”
“MiR-106b

is overexpressed in various types of cancers and is associated with the regulation of the carcinogenic processes. Using RT-PCR, we have identified overexpression of miRNA-106b in various melanoma cell lines (A375, Hs294t, SK-el28, SK-Mel 119, Mel 1241, Mel 1011 and Mel 928) as compared to its expression in normal human epidermal melanocytes (NHEM). The overexpression of miR-106b in melanoma cells (A375, Hs294t) was associated with greater cell proliferation capacity than NHEM. Treatment of A375 and Hs294t cells with anti-miR-106b resulted in inhibition of cell proliferation as well as G1-phase arrest. We determined the effects of grape seed proanthocyanidins (GSPs) on the expression of miRNA-106b and its underlying molecular targets. Treatment of A375 and Hs294t DNA Damage inhibitor cells with GSPs resulted in suppression of the levels of miRNA-106b, cytotoxicity, G1-phase arrest and reactivation of p21/WAF1/Cip1. Dietary GSPs significantly inhibited growth of A375 melanoma cell tumor xenografts in nude mice, which was associated with reduction in the levels of miRNA-106b, tumor cell proliferation and increases in the levels of p21/WAF1/Cip1 protein. These studies suggest that miRNA-106b plays a crucial role in melanoma growth and that GSPs act as an inhibitor of miR-106b thereby blocking melanoma growth in vitro and in vivo models.”
“HEV generally causes a self-limited acute infection and treatment remains supportive.


“To investigate the effect of Buyang Huanwu Decoction (BYH


“To investigate the effect of Buyang Huanwu Decoction (BYHWD) on estradiol (E-2) and Liproxstatin-1 chemical structure estradiol receptor (ER) in serum and brain in ovariectomized rats after middle cerebral artery occlusion (MCAO). Adult female rats were ovariectomized and focal cerebral ischemic was induced by MCAO. Rats were randomly divided into normal, ovariectomy (OVX), MCAO, OVX+MCAO, OVX+MCAO+E-2, and OVX+MCAO+BYHWD group. Rats were administered BYHWD 5 g/kg daily, estradiol valerate 500 mu g/kg per day or distilled water for 7 consecutive days. Neuronal function and infarct volume were measured on day

7 after artery occlusion, and E-2 and ER concentration in serum and brain were checked by enzyme-linked immunosorbent assay. BYHWD significantly improved the neurological behavior, reduced the infarction volume, increased E-2 concentration

in serum and brain, and increased ER concentration in the brain in ovariectomized rats after MCAO. The neuroprotective effects of BYHWD are associated with estrogen and its receptor.”
“Introduction: Klebsiella pneumonia (KP) is related to a metastatic phenomenon from the originally affected primary organ. About 28% of patients with pyogenic https://www.selleckchem.com/products/bix-01294.html liver abscess arising from KP suffer from metastatic complications. This study was done to define the clinical features of KP-induced prostate abscess. Methods: A total of 14 patients were diagnosed with prostate abscess based on clinical, laboratory examination and abdominopelvic computed tomography (CT) scan from 2007 to 2013. Results: Among these 14 patients, KP was the dominant causative microorganism in 6 patients Navitoclax (42.9%), followed by Esherchia coli in 2, Pseudomonas aeroginosa in 1, methicillin-resistant Staphyolcoccus aureus in 1, and no growth in either the urine or blood culture in 4. Four (66.7%) of the 6 KP induced-prostate abscess had other concurrent abscess sites besides the prostate: liver in 3, kidney in 1, and perianal area with endogenous endophthalmitis that ended in loss of vision in 1 patient. Conclusions: We report on the clinical features of KP-induced prostate abscess based on a small number of patients, which is the main limitation

of our study. We believe that if the causative organism of a prostate abscess was KP, more workup would be needed to rule out the presence of an abscess in other organs, especially in the liver. Abdominopelvic CT scan would be a proper imaging modality.”
“Several studies have indicated a strong association between asthma and aspiration of stomach contents. However, the complex association between these inflammatory processes has not been studied extensively in animal models. In the present study, we developed an animal model to evaluate the inflammatory cell, chemokine, and airway responses to asthma complicated by aspiration. The model was produced by sensitizing mice to cockroach allergens from house-dust extracts.

5-92 5) and 88 5% (95% CI: 69 8-97 6), respectively Conclusio

5-92.5) and 88.5% (95% CI: 69.8-97.6), respectively.\n\nConclusions:\n\nUsing of AhpC antigen for diagnosis of H. pylori infection is a useful noninvasive method, accurate in adolescents and children,

and can be used for the development of a stool antigen detection kit for H. pylori.”
“The high throughput screening mammalian neocortex displays significant plastic rearrangement in response to altered sensory input, especially during early postnatal development. It is believed that cyclic AMP-response element-binding (CREB) plays an important role in orchestrating the molecular events that guide neuroplastic change, although the details of its genomic targets during normal postnatal development or in response to sensory deprivation remain unknown. Here, we performed CREB chromatin immunoprecipitation (ChIP) from monkey area V1 tissue and hybridized enriched DNA fragments to promoter microarrays (ChIP chip analysis). Our goal was to determine and categorize the CREB regulon in monkey area V1 at two distinct developmental stages (peak of critical period vs. adulthood) and after 5 days of monocular enucleation (ME) at both ages. GDC-0973 molecular weight Classification of enriched candidates showed that the majority of isolated promoter loci (n = 795) were common to all four conditions. A particularly interesting group of candidates (n = 192) was specific to samples derived from enucleated

infant area V1. Gene ontology analysis of CREB targets during early postnatal development showed a subgroup of genes implicated in cytoskeleton-based structural modification. Analysis of messenger RNA expression (quantitative real-time-polymerase chain reaction) of candidate genes showed striking differences Pitavastatin research buy in expression profiles between infant and adult area V1 after ME. Our study represents the first extensive genomic analysis of CREB DNA occupancy in monkey neocortex and provides new insight into the multifaceted transcriptional role of CREB in guiding neuroplastic change.”
“Objective: To evaluate in vitro antioxidant and apoptotic activities of Cyperus rotundas (C. rotundas). Methods: The phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C. rotundas

aerial part were determined. In addition, these extracts were also investigated for their cytotoxic and apoptotic activities. The major compound of the methanol extract was isolated. Both methanol and aqueous extracts (300, 150, and 50 mu g/mL) were evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay system. However, 16, 8, and 4 mg/mL of each extract were tested to investigate their OH center dot formation scavenging potential. Aqueous extract (800, 400, and 200 mu g/mL) and methanol extract (350, 175, and 88 mu g/mL) were tested against lipid peroxidation, induced by 75 mu M H2O2. The cytotoxicity (by MTT assay) and cell DNA fragmentation of both extracts were evaluated towards K562 and L1210 cell lines.

These indices were correlated with the percentage of children mee

These indices were correlated with the percentage of children meeting clinic referral wait time targets and receiving surgery within the Pediatric Canadian Access Targets for Surgery. RESULTS: Across all SES quintiles, 33% of children exceeded their referral wait time targets, and 28% of children exceeded their surgical wait time targets. Indices of material or social deprivation

and age did not correlate with the time from referral to clinic consultation (P = .54, .40, and .58, click here respectively). Gender was statistically significant (P smaller than .001), but the difference was small (odds ratio = 0.87 for girls). Distance was also statistically significant (P = .005), and these differences translate into clinically meaningful differences in meeting wait time targets. Regarding completion of surgical procedures, material deprivation, distance, Blasticidin S nmr and gender did not correlate with longer wait times for surgery (P = .44, .09, .59, respectively). Social deprivation was statistically significant (P = .02) but not clinically significant. Increasing patient age was significantly associated with increased proportion of out-of-window wait times (P smaller than .001). SES did not affect the timeliness of completion of surgery even when the urgency of the surgery (priority level based on diagnosis) was considered.

CONCLUSIONS: SES does not predict the timeliness of delivery for pediatric surgical services.”
“Objective. The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity. Methods. Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label see more adalimumab + MTX. Patients

were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission. Results. Of 333 patients assessed, 278 (137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks (mean delta mTSS at week 52 = 2.56 vs 3.30, P smaller than 0.001). Conclusion.

With the application of the optimized protocol, four carnation cu

With the application of the optimized protocol, four carnation cultivars (‘Master’, ‘Calibra’, ‘Lamour’ and ‘Ofcar’) achieved regrowth percentage after cryopreservation ranging from 41 to 73 %. Ultrastructural observations investigated by using transmission electron microscopy showed that the cells encountered the stress during cryopreservation and the main MLN4924 molecular weight damages occurred during the dehydration step. For surviving cells, the most of the damaged cells could be repaired after recovery growth. This modified protocol will aid in the

long-term conservation of carnation germplasm and the ultrastructural studies will benefit for understanding the damage and recovery of the cells during cryopreservation.”
“Myo-inositol is important for Streptomyces growth and morphological differentiation. Genomic sequence analysis revealed a myo-inositol catabolic gene cluster in Streptomyces coelicolor. Disruption of the corresponding genes

in this cluster abolished the bacterial growth on myo-inositol as a single carbon source. The transcriptions of these genes were remarkably enhanced by addition of myo-inositol in minimal medium. A putative regulatory gene SCO6974, encoding a GntR family protein, is situated in the cluster. Disruption of SCO6974 significantly enhanced the transcription of myo-inositol catabolic genes. SCO6974 was shown to interact with the promoter regions of myo-inositol catabolic genes using electrophoretic mobility shift Citarinostat price assays. DNase I footprinting assays demonstrated that SCO6974 recognized a conserved palindromic sequence (A/T)TGT(A/C)N(G/T)(G/T)ACA(A/T). Sotrastaurin Base substitution of the conserved sequence completely abolished the binding of SCO6974 to the targets demonstrating that SCO6974 directly represses the transcriptions of myo-inositol catabolic genes. Furthermore, the disruption

of SCO6974 was correlated with a reduced sporulation of S. coelicolor in mannitol soya flour medium and with the overproduction of actinorhodin and calcium-dependent antibiotic. The addition of myo-inositol suppressed the sporulation deficiency of the mutant, indicating that the effect could be related to a shortage in myo-inositol due to its enhanced catabolism in this strain. This enhanced myo-inositol catabolism likely yields dihydroxyacetone phosphate and acetyl-CoA that are indirect or direct precursors of the overproduced antibiotics.”
“To investigate the effect of Auditory, Tactile, Visual and Vestibular stimulus (ATVV) on neuromotor development in preterm infants.\n\nFifty preterm infants born at 28-36 wk with a birth weight ranging from 1,000-2,000 g were recruited for the study. They were block randomized into a control group (n = 25) and study group (n = 25). New Ballard score was used for the baseline measurement of neuromaturity in both groups.

In our study, we included patients virologically suppressed ( big

In our study, we included patients virologically suppressed ( bigger than = 1 year), on antiretroviral therapy, without concomitant major neurocognitive confounders, receiving boosted lopinavir or darunavir as monotherapy (n=96) or as triple therapy with two nucleoside reverse transcriptase inhibitors (n=95). All patients underwent a comprehensive neuropsychological test battery (14 neuropsychological measures, covering seven domains). Both groups were compared in average score distributions and rates of neuropsychological

deficits. Similar comparisons were conducted only for patients with neurocognitive impairment. In the adjusted analysis, we found only small differences between groups in the entire sample: better verbal learning (p=0.02; d=0.28) and verbal recall scores (p smaller than TH-302 research buy 0.01; d=0.25) in patients on boosted protease inhibitor monotherapy and slightly better

motor skills with dominant hand (p=0.02; d=0.23) scores in patients on triple therapy. No greater proportion of deficits in the protease inhibitor monotherapy group was found in any neuropsychological measure. In neurocognitively impaired patients, we found similar outcomes in verbal learning, verbal recall, and motor skills with dominant hand but with larger effect sizes. Close similarities in the neurocognitive pattern between groups question the clinical relevance of the number of neuroactive see more drugs included in the regimen. These results also suggest that peripheral viral load control may be a good indicator of brain protection.”
“Background: The use of acellular dermal matrices has become increasingly popular in immediate and delayed tissue expander/implant-based breast reconstruction. However, it is unclear whether their use is associated with increased postoperative complication rates. Using the American College of Surgeons National Surgical Quality Improvement Program database, the authors assessed baseline differences in demographics

and comorbidities with and without acellular dermal matrix and determined whether postoperative complication rates varied. Methods: GW4869 concentration Using the national surgical database (2005 to 2011), tissue expander/implant-based breast reconstruction cases were extracted using Current Procedural Terminology codes. Differences in preoperative demographics and comorbidities were assessed using chi-square and t test analysis using SPSS. The authors analyzed variations in complication rates and determined whether demographics and comorbidities affected outcomes using multivariate logistical analysis. A post hoc power study was calculated. Results: Of 19,100 cases, 3301 involved acellular dermal matrix use. Overall complication rates were not statistically significant (acellular dermal matrix, 5.3 percent; non-acellular dermal matrix, 4.9 percent; p = 0.396). Several risk factors were statistically significant associated factors of complications.

Activation

Activation check details of the NK3R appears to recruit multiple pathways, including acetylation, and possibly histone deactylases, histone methylases, or DNA methylases to affect chromatin structure and gene expression. (C) 2012 Elsevier Inc. All rights reserved.”
“The depletion of cholesterol from membranes, mediated by beta-cyclodextrin (beta-CD) is well known and documented,

but the molecular details of this process are largely unknown. Using molecular dynamics simulations, we have been able to study the CD mediated extraction of cholesterol from model membranes, in particular from a pure cholesterol monolayer, at atomic resolution. Our results show that efficient cholesterol extraction depends on the structural distribution of the CDs on the surface of the monolayer. With a suitably oriented dimer, cholesterol is extracted spontaneously on a nanosecond time scale. Additional free

energy calculations reveal that the CDs have a strong affinity to bind to the membrane surface, and, by doing so, destabilize the local packing of cholesterol molecules making their extraction favorable. Our results have implications for the interpretation of experimental measurements, and may help in the rational design of efficient CD based nano-carriers.”
“The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous Selleck LY2603618 chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml).\n\nIn monolayers and 3-D Minusheet culture

chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the selleck pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 +/- 0.8 mu g/10(6) cells; mean +/-, SEM, but remained considerably lower than in monolayer cultures with/without Spongostan.\n\nOur results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days.

Single point mutations enhance the amyloidogenicity of TTR, causi

Single point mutations enhance the amyloidogenicity of TTR, causing familial amyloid cardiomyopathy, familial amyloid polyneuropathy,

and central nervous system selective amyloidosis. To date, nearly 200 X-ray crystal structures of TTR and their complexes have been solved. They have provided potential insights into its structure-function relationships with molecular partners, and its interactions with small molecule ligands that inhibit tetramer destabilization and amyloid formation. This review will focus on the key findings of the structural studies of TTR that provided atomic level description of its architecture, the mechanistic role of structural components involved in its function and misfolding, and the progress and limitations towards the design of selective inhibitors for TTR amyloidoses.”
“A diagnosis of invasive candidiasis can be achieved using conventional approaches (microscopy, Culture, serology), as well as new methods, including Selisistat molecular weight MEK inhibitor cancer antigen detection and polymerase chain reaction (PCR) assays. Most of the conventional approaches lack sensitivity, especially for obtaining a diagnosis of invasive candidiasis in immunocompromised patients. Antigen detection and PCR assays represent a valid alternative, in terms of their high potential sensitivity and specificity, but these

procedures still need to be standardized and evaluated in a large number of patients.”
“Marine Protected Areas MPA have been widely used over the last 2 decades to address human impacts on marine habitats within an ecosystem management context. Few studies have quantified recovery of temperate rocky reef communities following the cessation of scallop dredging or demersal trawling. This is critical information for the future management of these habitats to contribute towards conservation and fisheries targets.

The Lyme Bay MPA, in south west UK, has excluded towed demersal fishing gear from 206 km(2) of sensitive reef habitat using a Statutory Instrument since July 2008. To assess benthic recovery in this MPA we used a flying video array to survey macro epi-benthos annually from 2008 to 2011. 4 treatments (the New Closure, previously voluntarily Closed Controls and Near or Far Open to fishing Controls) were sampled to test a recovery hypothesis Proteasome inhibitor that was defined as ‘the New Closure becoming more similar to the Closed Controls and less similar to the Open Controls’. Following the cessation of towed demersal fishing, within three years positive responses were observed for species richness, total abundance, assemblage composition and seven of 13 indicator taxa. Definitive evidence of recovery was noted for species richness and three of the indicator taxa (Pentapora fascialis, Phallusia mammillata and Pecten maximus). While it is hoped that MPAs, which exclude anthropogenic disturbance, will allow functional restoration of goods and services provided by benthic communities, it is an unknown for temperate reef systems.

CONCLUSIONS The correlation between structure and function i

\n\nCONCLUSIONS. The correlation between structure and function is stronger in FDF and FDT compared with SAP. Correlations are strongest in temporal areas where glaucomatous damage tends to occur first. A better understanding of the structure-function

relationship should allow for improved detection and management of glaucoma patients. (Invest Ophthalmol Vis Sci. 2012; 53: 7553-7559) DOI:10.1167/iovs.12-10892″
“Currently available crosslinking methods for electrospun collagen nanofibers do not preserve the fibrous architecture over prolonged periods of time. In addition, electrospinning of collagen often involves solvents that lead to extensive protein denaturation. In this study, we demonstrate the advantage of acetic acid over 1,1,1,3,3,3 hexafluoroisopropanol (HFP) in preventing collagen denaturation. A novel photochemical https://www.selleckchem.com/products/SB-203580.html crosslinking method using rose bengal as the photoinitiator is also introduced. Using circular dichorism analyses, we demonstrate the fraction of collagen helical structure to

be significantly greater in acetic acid-spun fibers than HFP-spun fibers (28.9 +/- 5.9% vs. 12.5 +/- 2.0%, p < 0.05). GNS-1480 By introducing 0.1% (w/v) rose bengal into collagen fibers and subjecting these scaffolds to laser irradiation at a wavelength of 514 nm for 100 sec, biodegradable crosslinked scaffolds were obtained. Scaffold degradation as evaluated by soaking crosslinked collagen scaffolds in PBS at 37 degrees C, indicated a mass loss of 47.7 +/- 7.4% and 68.9 +/- 24.7% at day 7 and day 15, respectively. However, these scaffolds retained fibrous architecture for at least 21 days under physiological conditions. Neural stem cell line, C17.2, cultured on crosslinked collagen scaffolds proliferated after 7 days by forming a confluent layer of cells with extensive cellular projections that were indicative of neurite outgrowth. Taken together, these findings support the potential of acetic acid-electrospun photochemical crosslinked collagen nanofibers for neural tissue engineering. (C) 2010 Wiley Periodicals,

Inc. J Biomed Mater Res Part A: 95A: 276-282, 2010.”
“Every year about selleck chemicals 7 million people die from of various types of cancer, making this disease responsible for 12.5% of deaths worldwide. Consequently, there is an overwhelming demand to develop new, more potent and effective, anticancer drugs. Natural products represent the most valuable source with inexhaustible reserves, in which the researchers work could identify novel active agents that may serve as the leads and scaffolds for transformation into desperately needed efficacious drugs. This paper is devoted to reviewing some of the most outstanding achievements in the application of natural products as models and precursors for anticancer agents published in the post 2000 literature.

Current American Heart Association guidelines recommend standardi

Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Design: Randomized interventional study.

Setting: Preclinical animal laboratory. Subjects: Twenty-four 3-month-old female swine. MK-1775 ic50 Interventions: After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Measurements and Main Results: Forty-five-minute survival was higher in the coronary perfusion

pressure-20 VX 809 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 p53 inhibitor mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p smaller than 0.01). Total epinephrine dosing and defibrillation attempts were not different. Conclusions: Hemodynamic directed resuscitation targeting coronary perfusion pressures greater

than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival, when compared to resuscitation with depth of compressions guided to 33 mm or 51 mm and standard American Heart Association vasopressor dosing.”
“Background: This study aims to review our surgical results of elastofibroma dorsi. Methods: Between January 2005 and December 2012, a total of 42 patients (33 females, 9 males; mean age 59.7 years; range 31 to 77 years) who were operated in our clinic were included. All patients were admitted with complaints of pain, swelling or limited range of motions of the shoulder range except two cases who underwent thoracotomy for other reasons. Twenty three patients (55%) had bilateral tumors. All patients were operated. Results: Postoperative complications were seroma in six patients, pneumothorax in one and local recurrence in one at eight months.