Discriminating glioblastoma from solitary brain metastases on 3 Tesla magnetic resonance imaging: the roles of fractional anisotropy and mean diffusivity.

OBJECTIVE: This study determined the diagnostic value of diffusion tensor imaging (DTI) sequences using fractional anisotropy (FA) and mean diffusivity (MD) for discriminating glioblastoma (GBM) from solitary brain metastases (SBM) using 3 Tesla magnetic resonance imaging (MRI). PATIENTS AND METHODS: A retrospective study was conducted, including 40 patients who underwent biopsy or surgery and received a histological diagnosis of GBM or SBM between August 2020 and December 2021. All preoperative examinations were performed on 3 Tesla MRI using conventional and DTI sequences. Three regions of interest (ROIs) were placed to measure a solid tumor component, peritumoral edema, and the opposite normal white matter to evaluate FA and MD values. Parametric and nonparametric statistical tests were used to determine differences between GBM and SBM. The diagnostic value of significantly different parameters between the two tumor entities was analyzed using the receiver operating characteristic (ROC) curve. RESULTS: The FA value for peritumoral edema (eFA) in GBM cases was significantly larger than that in SBM cases (p < 0.05), with no significant difference in MD values. The FA and MD values for the solid tumor component (sFA and sMD, respectively) and the ratio of the sFA value to the FA value of the opposite normal white matter (rFAs/n) in GBM cases were significantly larger than those in SBM cases (p < 0.05). Combining the sFA and sMD values provided the highest area under the ROC curve (AUC) value of 0.96, with a sensitivity, specificity, positive predictive value, and negative predictive value of 85.2%, 100%, 85.2%, and 87.1%, respectively, for distinguishing GBM from SBM. CONCLUSIONS: MRI parameters, including sFA, sMD, eFA, and rFAs/n, are useful for differentiating between GBM and SBM. The combination of sFA and sMD may increase the diagnostic performance of MRI for these two tumor entities.

Discrimination between glioblastoma and solitary brain metastasis: a quantitative analysis based on FLAIR signal intensity.

OBJECTIVE: This study determined the diagnostic performance of fluid-attenuated inversion recovery (FLAIR) signal intensity (SI) in discriminating between glioblastoma (GBM) and solitary brain metastasis (SBM). PATIENTS AND METHODS: We recruited 40 patients with a histologically confirmed diagnosis of GBM or SBM who underwent conventional 3 Tesla magnetic resonance imaging before surgery or biopsy between August 2020 and January 2022. Three regions of interest were placed to assess FLAIR SI: the enhancing region (eFLAIR), the peritumoral region (pFLAIR), and the contralateral normal white matter (nFLAIR). The diagnostic performance of significantly different parameters between the two tumor entities was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: The pFLAIR SI was significantly lower in GBM than in SBM (p < 0.05). The eFLAIR SI and the SI ratio eFLAIR and nFLAIR (e/nFLAIR) were significantly higher in GBM than in SBM (p < 0.05). On ROC curve analysis, the e/nFLAIR ratio provided the highest area under the curve value of 81%, with a sensitivity of 80.8% and a specificity of 85.7%, for distinguishing between the two tumor types. CONCLUSIONS: The eFLAIR, pFLAIR, and e/nFLAIR parameters are useful for differentiating between GBM and SBM.

New trematode species Lecithostaphylus halongi n. sp. (Zoogonidae, Microphalloidea) and Gymnotergestia strongyluri n. sp. (Fellodistomidae, Gymnophalloidea) from beloniform fishes in Vietnam.

In this study we described two new trematode species, Lecithostaphylus halongi n. sp. (Zoogonidae, Lecithostaphylinae) and Gymnotergestia strongyluri n. sp. (Fellodistomidae, Tergestiinae), on the basis of morphological and molecular data. Adult worms of these two species were collected from, respectively, Hemiramphus spp. (Hemiramphidae) and Strongylura strongylura (Belonidae) caught in the coastal waters of Vietnam. Adult worms of L. halongi n. sp. are morphologically close to Lecithostaphylus gibsoni Cribb, Bray & Barker, 1992 ex Abudefduf whitleyi from Heron Island and Lecithostaphylus depauperati Yamaguti, 1970 ex Hemiramphus depauperatus from Hawaii, but differ from these species in having a larger cirrus sac and a different arrangement of vitelline fields. They also differ from Lecithostaphylus brayi Cabañas-Granillo, Solórzano-García, Mendoza-Garfias & Pérez-Ponce de León, 2020 in the 28S ribosomal DNA (rDNA) sequence data at the interspecific level. Adult worms of G. strongyluri n. sp. ex S. strongylura are morphologically similar to Gymnotergestia chaetodipteri, the only previously known species of this genus, described from Chaetodipterus faber in Jamaica. The new species differs from G. chaetodipteri in body shape, testicular arrangement and the size of the pharynx and eggs. The 28S rDNA-based phylogenetic analysis indicates that G. strongyluri n. sp. is closely related to Tergestia spp., rendering Tergestia paraphyletic. Genetic divergence values between G. strongyluri n. sp. and Tergestia spp. are similar to those among species in the genera Tergestia, Steringophorus and Proctoeces. Our molecular results indicate that G. strongyluri n. sp. and Tergestia spp. may belong the same genus, but additional molecular data are needed for the final conclusion.

Correction to: Morphometric and molecular analyses of Carassotrema koreanum park 1938 and Elonginurus mugilus Lu 1995 (Digenea: Haploporidae) Srivastava, 1937 from the Russian Far East and Vietnam.

The original version of this article contained mistake in the accession number found in Table 1. Correct accession numbers are presented here.

Morphometric and molecular analyses of Carassotrema koreanum Park 1938 and Elonginurus mugilus Lu 1995 (Digenea: Haploporidae) Srivastava, 1937 from the Russian Far East and Vietnam.

Adult worms that belong to Carassotrema Park 1938 and Elonginurus Lu, 1955 were found in the intestine of Carassius gibelio Bloch, 1782 from the southern Russian Far East and Mugil cephalus Linnaeus, 1758 from northern Vietnam, respectively. Morphometric parameters, geographic location and host species composition of these worms correspond to Carassotrema koreanum Park 1938, which is a known parasite of cyprinid fish in Korea, Japan and China, and Elonginurus mugilus Lu, 1955, first described from M. cephalus in China. The validity of Carassotrema ginezinskajae Kulakova, Ha Ky, 1976, a synonym of C. koreanum, first described from Spinibarbichthys denticulatus Oshima, 1926 in Vietnam, supported the morphometric data. Phylogenetic analysis based on combined ITS2 ribosomal DNA (rDNA) and 28S rRNA indicated that C. koreanum and E. mugilus belong to the subfamily Waretrematinae and are closely related to the genera Skrjabinolecithum and Parasaccocoelium, respectively. Species similarity, revealed through molecular analysis, agreed with the generic diagnoses for Parasaccocoelium and Elonginurus, as well as for Carassotrema and Skrjabinolecithum.

Morphological and molecular data for species of Lecithaster Lühe, 1901 and Hysterolecithoides Yamaguti, 1934 (Digenea: Lecithasteridae) from fish of East Asia and phylogenetic relationships within the Hemiuroidea Looss, 1899.

Four representatives of the genus Lecithaster and one representative of the genus Hysterolecithoides were found during investigation of the trematode fauna of fish species in Vietnamese, Japanese and eastern coastal waters of the Russian Far East. Based on morphometric data, adult trematodes from Vietnamese Strongylura strongylura and Russian Acanthogobius flavimanus were identified as Lecithaster confusus, trematodes from Vietnamese Hemirhamphus marginatus as L. sayori and from osmerid fishes as L. salmonis. Further, a single specimen of Lecithaster sp. and representatives of Hysterolecithoides epinepheli were found in Vietnamese Siganus fuscescens. Morphological and molecular data, including 18S ribosomal DNA (rDNA) V4 fragment, 28S rDNA D1-D3 fragment, internal transcribed spacers (ITS) and a mitochondrial COI gene fragment were analysed for Lecithaster spp. The results revealed that L. sayori and L. salmonis are not synonyms of L. stellatus and L. gibbosus, respectively, but that Hysterolecithoides frontilatus and H. guangdongensis are junior synonyms of H. epinepheli. The 28S-rDNA-based phylogenetic tree of Hemiuroidea showed a distinct position for the genus Lecithaster with internal differentiation into three subclades, including L. confusus, L. sayori and Lecithaster sp. within the first subclade, L. mugilis and L. sudzuhensis within the second subclade and L. salmonis and L. gibbosus within the third subclade. Bayesian phylogenetic reconstructions of Hemiuroidea showed four clades for members of Hemiuridae and Lecithasteridae. The first clade consisted of Hemiuridae representatives and the second clade represented the genus Lecithaster. The third clade included genera Aponurus and Lecithophyllum (Lecithasteridae) and the fourth clade combined members of lecithasterid Quadrifoliovariinae and Hysterolecithinae and hemiurid Opisthadeninae and Bunocotylidae with high statistical support.

Litsea cubeba leaf essential oil from Vietnam: chemical diversity and its impacts on antibacterial activity.

The threat of bacterial resistance to antibiotics has created an urgent need to develop new antimicrobials. The aim of this study was to characterize the chemical diversity of Litsea cubeba leaf essential oil (EO) and its impacts on the antibacterial activity against pathogenic bacteria. Essential oils collected from seven provinces in North Vietnam (n = 25) were characterized by their high content in either 1,8-cineole or linalool. Linalool-type EOs were more effective against the eight bacterial strains tested than 1,8-cineole-type. Oil samples, LC19 (50% 1,8-cineole) and BV27 (94% linalool), were selected to investigate their antibacterial mechanisms against Escherichia coli. A strong bactericidal effect was observed after 4 and 2 h of exposure respectively. Microscopic analysis of treated E. coli cultures clearly showed that EOs caused changes in cell morphology, loss of integrity and permeability of the cell membrane, as well as DNA loss. However, the effects of both EOs were distinct. LC19 mostly affected cell membrane, led to a significant cell filamentation rate and altered cell width, whereas BV27 damaged cell membrane integrity leading to cell permeabilization and altered nucleoid morphology with the appearance of spot and visibly altered compaction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study aimed to characterize the chemical diversity of Litsea cubeba leaf essential oil (EO) and its impacts on its antibacterial activity. Two major chemotypes (1,8-cineole or linalool rich) were identified in North Vietnam and both were bactericidal against several pathogenic bacteria. A distinct inhibitory effect of EO samples on Escherichia coli was observed. 1,8-cineole-rich sample (LC19) affected cell membrane, led to cell filamentation and perturbation of cell width, while the linalool-rich one (BV27) induced damages in the cell membrane and changes in the nucleoid morphology. The study demonstrates the importance of considering chemotype variations in terms of chemical composition as well as the mode of action.

Advanced capabilities for materials modelling with Quantum ESPRESSO.

Quantum EXPRESSO is an integrated suite of open-source computer codes for quantum simulations of materials using state-of-the-art electronic-structure techniques, based on density-functional theory, density-functional perturbation theory, and many-body perturbation theory, within the plane-wave pseudopotential and projector-augmented-wave approaches. Quantum EXPRESSO owes its popularity to the wide variety of properties and processes it allows to simulate, to its performance on an increasingly broad array of hardware architectures, and to a community of researchers that rely on its capabilities as a core open-source development platform to implement their ideas. In this paper we describe recent extensions and improvements, covering new methodologies and property calculators, improved parallelization, code modularization, and extended interoperability both within the distribution and with external software.

Antibacterial activity of Litsea cubeba (Lauraceae, May Chang) and its effects on the biological response of common carp Cyprinus carpio challenged with Aeromonas hydrophila.

AIMS: The aims of this study were to characterize the antibacterial activity and the chemotype of Litsea cubeba leaf essential oil (EO) harvested in North Vietnam and to investigate the biological effects induced by the leaf powder on growth, nonspecific immunity and survival of common carp (Cyprinus carpio) challenged with Aeromonas hydrophila. METHODS AND RESULTS: The EO showed the prevalence of linalool (95%, n = 5). It was bactericidal against the majority of tested strains, with minimum inhibitory concentrations ranging from 0·72 to 2·89 mg ml(-1) (Aer. hydrophila, Edwarsiella tarda, Vibrio furnissii, Vibrio parahaemolyticus, Streptococcus garvieae, Escherichia coli, Salmonella Typhimurium). The fish was fed with 0 (control), 2, 4 and 8% leaf powder supplementation diets for 21 days. Nonspecific immunity parameters (lysozyme, haemolytic and bactericidal activities of plasma) were assessed 21 days after feeding period and before the experimental infection. Weight gain, specific growth rate and feed conversion ratio were improved by supplementation of L. cubeba in a dose-related manner, and a significant difference appeared at the highest dose (8%) when compared to the control. The increase in plasma lysozyme was significant for all the treated groups. Haemolysis activity was higher for the groups fed with 4 and 8% plant powder. Antibacterial activity increased significantly for the 8% dose only. CONCLUSIONS: Litsea cubeba leaf powder increased nonspecific immunity of carps in dose-related manner. After infection with Aer. hydrophila, survivals of fish fed with 4 and 8% L. cubeba doses were significantly higher than those fed with 2% dose and the control. SIGNIFICANCE AND IMPACT OF THE STUDY: A range of 4-8% L. cubeba leaf powder supplementation diet (from specific linalool-rich chemotype) can be used in aquaculture to reduce antibiotic burden and impacts of diseases caused by Aer. hydrophila.

Reduced turn-around time for Mycobacterium tuberculosis drug susceptibility testing with a proportional agar microplate assay.

Multidrug-resistant tuberculosis is a major issue worldwide; however, accessibility to drug susceptibility testing (DST) is still limited in developing countries, owing to high costs and complexity. We developed a proportion method on 12-well microplates for DST. The assay reduced the time to results to <12 days and <10 days when bacterial growth was checked with the naked eye or a microscope, respectively. Comparison with the Canetti-Grosset method showed that the results of the two assays almost overlapped (kappa index 0.98 (95% CI 0.91-1.00) for isoniazid, rifampicin, streptomycin; and kappa index 0.92 (95% CI 0.85-0.99) for ethambutol). The sequencing of genes involved in drug resistance showed similar level of phenotype-genotype agreement between techniques. Finally, measurement of the MICs of rifampicin and ethambutol suggests that the currently used critical ethambutol concentration should be revised, and that the current molecular drug susceptibility tests for rifampicin need to be re-evaluated, as in vitro rifampicin-sensitive isolates could harbour drug resistance-associated mutation(s).

Synthesis of and evaluation of lipid A modification by 4-substituted 4-deoxy arabinose analogs as potential inhibitors of bacterial polymyxin resistance.

Three sets of novel 4-deoxy-l-arabinose analogs were synthesized and evaluated as potential inhibitors of the bacterial resistance mechanism in which lipid A, on the outer membrane, is modified with 4-amino-4-deoxy-l-arabinose (l-Ara4N). One compound diminished the transfer of l-Ara4N onto lipid A. These results suggest that small molecules might be designed that would effect the same reversal of bacterial resistance observed in genetic knockouts.

Postnatal ontogeny of skeletal muscle protein synthesis in pigs.

The neonatal period is characterized by rapid growth and elevated rates of synthesis and accretion of skeletal muscle proteins. The fractional rate of muscle protein synthesis is very high at birth and declines rapidly with age. The elevated capacity for muscle protein synthesis in the neonatal pig is driven by the high ribosome content and, together with an increased efficiency of the translation process, promotes accelerated protein synthesis rates. Feeding profoundly stimulates muscle protein synthesis in neonatal pigs and the response decreases with age. The feeding-induced stimulation of muscle protein synthesis is modulated by an enhanced sensitivity to the postprandial increase in insulin and amino acids. The developmental decline in the response to insulin and amino acids parallels a marked decrease in the feeding-induced activation of translation initiation factors that regulate the binding of mRNA to the 40S ribosomal complex. The abundance and activation of many known positive regulators of the nutrient- and insulin-signaling pathways that are involved in translation initiation are high, whereas those of many negative regulators are low in skeletal muscle of younger pigs. Thus, the activation and(or) abundance of the positive regulators, such as the insulin receptor, insulin receptor-substrate-1, phosphoinositide-3 kinase, phosphoinositide-dependent kinase-1, protein kinase B, mammalian target of rapamycin, raptor, ribosomal protein S6 kinase-1, eukaryotic initiation factor (eIF) 4E-binding protein 1, and eIF4E associated with eIF4G, are greater in 7-d-old pigs than in 26-d-old pigs. The activation of negative regulators, including protein tyrosine phosphatase-1B, phosphatase and tensin homologue deleted on chromosome 10, protein phosphatase 2A, and tuberous sclerosis complex 1/2, are lower in 7-d-old pigs than in 26-d-old pigs. Thus, the developmental decline in the stimulation of skeletal muscle protein synthesis by insulin and amino acids is due in part to the developmentally related decrease in the activation of the signaling pathways that lead to translation initiation.

Quality of life in a random sample of community dwelling older patients with essential tremor.

STUDY OBJECTIVE - Nested case-control study aimed to assess the quality of life of community dwelling participants aged 65 years or over with newly diagnosed Essential Tremor (ET). METHODS AND RESULTS - Thirty-two participants with newly diagnosed ET and 32 age and gender matched controls were administered the Rand-SF36 quality of life questionnaire. Medical co-morbidities were also assessed in the two groups. Results - Participants with ET had significantly lower scores in the physical function, role limitation because of physical function, role limitation as a result of emotional problem, pain, and energy/vitality subscales of the Rand-SF36 when compared with controls. CONCLUSIONS - Older patients with newly diagnosed ET have poorer quality of life than their community dwelling counterparts without ET.

Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy.

BACKGROUND: We aimed to investigate the associations between androgen status and markers of liver disease severity and to determine the effect of interferon-alpha (IFN-alpha) treatment on sex hormone levels in the context of hepatitis C infection. METHODS: We audited liver biopsy and sex hormone data from 35 men with chronic hepatitis C and a separate group of 11 men with hepatitis C who received IFN-alpha treatment at Fremantle Hospital. RESULTS: We found that men with low fibrosis scores (0-2) on the modified Knodell histological activity index were more likely to have lower sex hormone-binding globulin (SHBG) levels (38.2 +/- 13.2 vs 66.6 +/- 43.3 nmol/L, P < 0.001) and higher free testosterone levels (380.4 +/- 102.0 vs 255.9 +/-83.0 pmol/L, P = 0.01) than those with higher fibrosis scores (3-6). SHBG directly correlated with fibrosis scores (r = 0.37, P = 0.032). Free testosterone levels inversely correlated with liver fibrosis scores (r = -0.43, P = 0.011). A transient reduction in total testosterone of 5.7 +/- 4.2 nmol/L (P = 0.014) occurred within the first 6 months of IFN-alpha therapy although free testosterone was unaffected. CONCLUSION: More severe liver disease was associated with lower free testosterone and higher SHBG. IFN-alpha therapy reduced total testosterone but not to hypogonadal levels, with no decline in free testosterone. These data suggest that liver disease in hepatitis C infection modulates androgen status indirectly via increased SHBG. Screening for androgen deficiency in the context of hepatitis C infection should selectively target men with more severe liver disease or documented higher grade fibrosis.

Challenges of assuring crew safety in space shuttle missions with international cargoes.

The top priority in America's manned space flight program is the assurance of crew and vehicle safety. This priority gained greater focus during and after the Space Shuttle return-to-flight mission (STS-26). One of the interesting challenges has been to assure crew safety and adequate protection of the Space Shuttle, as a national resource, from increasingly diverse cargoes and operations. The control of hazards associated with the deployment of complex payloads and cargoes has involved many international participants. These challenges are examined in some detail along with examples of how crew safety has evolved in the manned space program and how the international partners have addressed various scenarios involving control and mitigation of potential hazards to crew and vehicle safety.

Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs.

In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feeding response and its developmental decline can be reproduced by insulin infusion, suggesting that an altered responsiveness to insulin is a primary determinant of the developmental decline in the stimulation of protein synthesis by feeding. In this study, 7- and 26-day-old pigs were either fasted overnight or fed porcine milk after an overnight fast. We examined the abundance and degree of tyrosine phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and IRS-2 in skeletal muscle and, for comparison, liver. We also evaluated the association of IRS-1 and IRS-2 with phosphatidylinositol 3-kinase (PI 3-kinase). The abundance of IR protein in muscle was twofold higher at 7 than at 26 days, but IRS-1 and IRS-2 abundances were similar in muscle of 7- and 26-day-old pigs. The feeding-induced phosphorylations were greater at 7 than at 26 days of age for IR (28- vs. 13-fold), IRS-1 (14- vs. 8-fold), and IRS-2 (21- vs. 12-fold) in muscle. The associations of IRS-1 and IRS-2 with PI 3-kinase were also increased by refeeding to a greater extent at 7 than at 26 days (9- vs. 5-fold and 6- vs. 4-fold, respectively). In liver, the abundance of IR, IRS-1, and IRS-2 was similar at 7 and 26 days of age. Feeding increased the activation of IR, IRS-1, IRS-2, and PI 3-kinase in liver only twofold, and these responses were unaffected by age. Thus our findings demonstrate that the feeding-induced activation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with development. Further study is needed to ascertain whether the developmental decline in the feeding-induced activation of early insulin-signaling components contributes to the developmental decline in translation initiation in skeletal muscle.

Analysis of the constitution of the beer yeast genome by PCR, sequencing and subtelomeric sequence hybridization.

The lager brewing yeasts, Saccharomyces pastorianus (synonym Saccharomyces carlsbergensis), are allopolyploid, containing parts of two divergent genomes. Saccharomyces cerevisiae contributed to the formation of these hybrids, although the identity of the other species is still unclear. The presence of alleles specific to S. cerevisiae and S. pastorianus was tested for by PCR/RFLP in brewing yeasts of various origins and in members of the Saccharomyces sensu stricto complex. S. cerevisiae-type alleles of two genes, HIS4 and YCL008c, were identified in another brewing yeast, S. pastorianus CBS 1503 (Saccharomyces monacensis), thought to be the source of the other contributor to the lager hybrid. This is consistent with the hybridization of S. cerevisiae subtelomeric sequences X and Y' to the electrophoretic karyotype of this strain. S. pastorianus CBS 1503 (S. monacensis) is therefore probably not an ancestor of S. pastorianus, but a related hybrid. Saccharomyces bayanus, also thought to be one of the contributors to the lager yeast hybrid, is a heterogeneous taxon containing at least two subgroups, one close to the type strain, CBS 380T, the other close to CBS 395 (Saccharomyces uvarum). The partial sequences of several genes (HIS4, MET10, URA3) were shown to be identical or very similar (over 99%) in S. pastorianus CBS 1513 (S. carlsbergensis), S. bayanus CBS 380T and its close derivatives, showing that S. pastorianus and S. bayanus have a common ancestor. A distinction between two subgroups within S. bayanus was made on the basis of sequence analysis: the subgroup represented by S. bayanus CBS 395 (S. uvarum) has 6-8% sequence divergence within the genes HIS4, MET10 and MET2 from S. bayanus CBS 380T, indicating that the two S. bayanus subgroups diverged recently. The detection of specific alleles by PCR/RFLP and hybridization with S. cerevisiae subtelomeric sequences X and Y' to electrophoretic karyotypes of brewing yeasts and related species confirmed our findings and revealed substantial heterogeneity in the genome constitution of Czech brewing yeasts used in production.

Fractures of the calcaneus.

Fractures of the calcaneus (os calcis) are the most common of tarsal bone fractures, with an overall prevalence of approximately 2%. Despite increased experience with these types of fractures, however, there is considerable debate regarding their treatment and overall management. Controversies remain regarding the most appropriate classification system, treatment options, indications for surgery, surgical approaches, and post-operative management. This article presents a rational approach to the treatment of os calcis fractures based on current and past literature and the authors' preferred methods of treatment.

Genetic identification of Saccharomyces bayanus var. uvarum, a cider-fermenting yeast.

Twenty-one Saccharomyces strains isolated from a cider process were analysed in terms of karyotypes, Y' S. cerevisiae sequence occurrence, rDNA structure and cross-fertility with species tester strains. A strong predominance of S. bayanus var. uvarum G. Naumov was found (18 strains vs. three S. cerevisiae). Among the S. bayanus var. uvarum, only three strains proved to contain species-specific Y' S. cerevisiae sequences.