Clinician Perspectives on Palliative Care for People with Hepatocellular Carcinoma: Facilitators of and Barriers to Referral.

(1) Background: Little is known about facilitators of and barriers to palliative care referral for people with hepatocellular carcinoma (HCC). The objective of this study is to identify facilitators and barriers of palliative care referral described by HCC-treating clinicians. (2) Methods: Semi-structured interviews (n = 16) were conducted with HCC-treating clinicians at two centers, focusing on referral patterns, palliative care needs, and disease course. A code book was created, axial coding was used to code all interviews, and selective coding was used to identify facilitators and barriers of palliative care referral. (3) Results: Facilitators included helpfulness at times of transition; help with management of certain symptoms; provision of psychosocial support; and positive experiences with referral. Barriers included feasibility concerns; lack of information about palliative care and who is appropriate; lack of symptoms requiring outside referral; and concerns that palliative care conveys loss of hope. (4) Conclusions: Participants noted the helpfulness of palliative care at specific points in the disease trajectory and cited barriers related to feasibility, lack of need, lack of awareness, and loss of hope. The results show actionable issues that can be addressed in future research to leverage the benefits of and overcome the barriers to palliative care for people with HCC.

The Prevalence and Impact of Low Back Pain Among Anaesthesia Care Providers in South-South, Nigeria.

Background: Low back pain (LBP) is a common musculoskeletal disorder, that significantly impedes productivity. This study aims to ascertain the risk factors responsible for developing low back pain and the impact on personal workplace service delivery among Anesthetist's practicing in Rivers and Bayelsa States of Nigeria. Methodology: A cross-sectional survey was conducted, A self-administered questionnaire reflecting the modified Oswestry Disability Index (ODI) was used to detect the risk factors and assess the severity and impact of low back pain on this group of professionals. The prevalence of low back pain was calculated and described by using frequency tables. A multivariate logistic regression model was fitted to identify factors associated with the prevalence of low back pain. Significance was considered at p<0.05 with a 95% confidence interval. Results: A total of 65 anesthetist's responded, giving a response rate of 90%. There were more males (52.3%) than females (47.7%). The majority (69.2%) of those who responded had low back pain, more in females (53.3%) compared to males (46.7%) although not significant. (P=0.994); Majority had moderate pain 58.6%, 22.7% severe and 20.5% mild pain. There was no association between low back pain and age (P=0.130), gender(P=0.994), marital status (P=0.333) and BMI (P=0.164). Bending (P=0.032), lifting (P=0.024), and standing(P=0.016) were predictive variables for low back pain and were statistically significant P<0.05. Conclusion: Using the Oswestry pain assessment tool for LBP, the estimated prevalence of low back pain was more than fifty percent among the respondents. In this study, frequent bending and twisting, prolonged standing, and lifting were important significant associated factors in the development of LBP among anesthetist's.

Understanding emerging regulation: The role of frontal electroencephalography asymmetry and negative affectivity.

The present study examined frontal electroencephalography (EEG) asymmetry and negative affectivity (NA) as predictors of infant behaviors during the Still-Face Paradigm (SFP). It was hypothesized that infants with lower NA subscale scores who also demonstrate greater left frontal activation would exhibit more frequent social engagement and self-soothing behaviors during the SFP. Mothers reported infant temperament at 6-12 months of age (N = 62), and EEG was recorded during a baseline task and the SFP. Social engagement, distress, and self-soothing behaviors were coded during the SFP. A three-factor solution emerged based on exploratory factor analysis of eight infant behaviors. After considering bivariate relations, multiple regression analyses predicting the behavior factor labeled social engagement (containing vocalizations and handwaving; average factor loading = .56) were conducted separately for asymmetry and NA subscales, controlling for infant sex and age. The SFP asymmetry predicted social engagement after controlling for covariates and baseline asymmetry; however, NA subscales (falling reactivity and distress to limitations) did not uniquely explain significant variance. These findings highlight the importance of frontal EEG asymmetry in contributing to emerging social engagement and regulation in infancy. Implications include potentially utilizing asymmetry markers as screening and intervention targets in the first year of life.

What can trauma patients' experiences and perspectives tell us about the perceived quality of trauma care? a qualitative study set within the UK National Health Service.

The global drive for improvements in the efficiency and quality of healthcare has led to the development of frameworks to assist in defining and measuring 'good quality care'. However, such frameworks lack a systematic or meaningful definition of what 'good quality care' means from the patients' perspective. The present research provides an in-depth analysis of patients' experiences in a hospital setting from a quality of care perspective. Forty-five adults (aged 16-70) hospitalised in one of four UK NHS trusts following an unintentional injury were interviewed about their experiences of care. The findings show variability in perceived quality of care within the same hospital episode which cannot be meaningfully captured by existing frameworks. The context of trauma care (e.g. distressing nature of injury, patient vulnerability, expectations of hospitalisation and participants' interaction with different service providers) defined the care experience and the value of being 'cared for'. Participants identified some aspects of good and care which related to holistic, person-centred and personalised care beyond the medical needs. Participants discussed the value of being understood, staff thinking of their needs beyond hospitalisation, staff trying 'their best' despite constrains of current care, having their emotional needs recognised and addressed and staff competence. Patients reported also poor quality of care and 'not being cared for' by specific staff groups which they expected to fulfil this role, rushed and unsympathetic care, lack of recognition for emotional impact of injury mapped onto existing quality frameworks e.g. safety, equity, accessibility and patient-centeredness as well as quality of interaction with providers, empathetic care which extended beyond medical needs, coordination of care, and the positivity of care delivery as important dimensions of quality care with implications for their recovery. The findings have implications for quality frameworks and theoretical definitions of quality of care; they demonstrate the importance of patient experience in addition to clinical effectiveness and safety as an essential dimension of quality care. In terms of practice, the findings support the need to incorporate knowledge and training of injured adults' psychological needs, and the value of interaction with professionals as a patient defined dimension of the quality of care.

Did you really need to ask? Cultural variation in emotional responses to providing solicited social support.

Most prior research on culture and the dynamics of social support has focused on the emotional outcomes for social support recipients. Though an existing body of research has identified cross-cultural differences in the emotional correlates of receiving different types of social support, researchers have seldom examined possible cultural differences in the experience of social support providers. This study used the Day Reconstruction Method to examine cultural differences in the emotional correlates of the provision of solicited and unsolicited and emotional and informational social support in the daily lives of Singaporean (n = 79) and American (n = 88) participants. Singaporean participants reported providing more social support overall. Regardless of culture, participants reported more positive emotion (affection, happiness) and less negative emotion (anger, anxiety) when they provided emotional social support. Also, multilevel modeling analyses revealed a 3-way interaction between culture, social support provision, and social support solicitation, indicating cultural differences in negative emotional responses to providing solicited social support. Specifically, results suggest that attempts to provide more solicited social support were associated with more negative emotions in the U.S. In contrast, provider negative emotions were highest in Singapore when the provider did not meet the recipient's request for support. Patterns of cultural differences in social support provision are dissimilar to-rather than simply mirroring-those found in published research on social support receipt, highlighting the importance of studying social support provision as a distinct phenomenon.

Early risk factors for depression, anxiety and post-traumatic distress after hospital admission for unintentional injury: Multicentre cohort study.

OBJECTIVE: To quantify psychological morbidity and identify baseline factors associated with depression, anxiety and post-traumatic distress symptoms up to 12 months post-injury. METHODS: Multicentre cohort study of 668 adults, aged 16 to 70, admitted to 4 UK NHS hospital trusts. Data on injury, socio-demographic characteristics and health status was collected at recruitment. Depression, anxiety and post-traumatic distress were measured at 1, 2, 4 and 12 months post-injury. Multilevel linear regression assessed associations between patient and injury characteristics and psychological outcomes over 12 months follow-up. RESULTS: Depression, anxiety and post-traumatic distress scores were highest 1 month post-injury, and remained above baseline at 2, 4 and 12 months post-injury. Moderate or severe injuries, previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age (45-64 years), greater deprivation and lower pre-injury quality of life (QoL) were associated with higher depression scores post-injury. Previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age, greater deprivation and lower pre-injury QoL were associated with higher anxiety scores post-injury. Traffic injuries or injuries from being struck by objects, multiple injures (≥3), being female, previous psychiatric diagnoses, higher pre-injury anxiety scores and greater deprivation were associated with higher post-traumatic distress scores post-injury. CONCLUSION: A range of risk factors, identifiable shortly after injury, are associated with psychological morbidity occurring up to 12 months post-injury in a general trauma population. Further research is required to explore the utility of these, and other risk factors in predicting psychological morbidity on an individual patient basis.

Moisture vapour permeable gloves extend thermal endurance and safe work time more than other similarly permeable chemical-biological ancillary protective items.

Working in Chemical Biological (CB) protective equipment causes thermoregulatory strain by restricting evaporative cooling. We quantified which impermeable ancillary items [gloves(G), body armour liner(BAL), respirator(R) and overboots(OB)] imposed the greatest and the least thermoregulatory strain through restricting evaporative cooling. The study was a five-condition repeated-measures design with male volunteers (n = 13) who stepped intermittently with recovery periods in a desert-like environment (40.5 °C, 20% rh). Conditions varied in the ensemble worn, with a matched weight secured to the area when an item was not worn: CON(CB suit plus all items), NR(no R), NBAL(no BAL [170g liner]), NG(no G) and NOB(no OB). The greatest reduction in thermoregulatory strain compared with CON occurred in NG when the rise of rectal temperature was attenuated by 0.37 °C.hr-1 (p < .001), extending tolerance time by 21.3% (p < .05) and improving perceived thermal comfort. The least improvement occurred for NOB. It is recommended that the G permeability be examined further. Practitioner summary: Thermoregulatory strain was quantified when wearing impermeable protective equipment. The thermal burden of intermittent exercise in desert-like environments was best alleviated by removing gloves compared to removing a respirator, overboots or body armour liner. Reducing the evaporative resistance of materials used for such kit, particularly gloves, should be investigated.

The impact of psychological factors on recovery from injury: a multicentre cohort study.

PURPOSE: Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults. METHODS: A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values. RESULTS: A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance. CONCLUSIONS: Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury.

Psychological morbidity and health-related quality of life after injury: multicentre cohort study.

PURPOSE: To demonstrate the impact of psychological morbidity 1 month post-injury on subsequent post-injury quality of life (HRQoL) in a general injury population in the UK to inform development of trauma care and rehabilitation services. METHODS: Multicentre cohort study of 16-70-year-olds admitted to 4 UK hospitals following injury. Psychological morbidity and HRQoL (EQ-5D-3L) were measured at recruitment and 1, 2, 4 and 12 months post-injury. A reduction in EQ-5D compared to retrospectively assessed pre-injury levels of at least 0.074 was taken as the minimal important difference (MID). Multilevel logistic regression explored relationships between psychological morbidity 1 month post-injury and MID in HRQoL over the 12 months after injury. RESULTS: A total of 668 adults participated. Follow-up rates were 77% (1 month) and 63% (12 months). Substantial reductions in HRQoL were seen; 93% reported a MID at 1 month and 58% at 12 months. Problems with pain, mobility and usual activities were commonly reported at each time point. Depression and anxiety scores 1 month post-injury were independently associated with subsequent MID in HRQoL. The relationship between depression and HRQoL was partly explained by anxiety and to a lesser extent by pain and social functioning. The relationship between anxiety and HRQoL was not explained by factors measured in our study. CONCLUSIONS: Hospitalised injuries result in substantial reductions in HRQoL up to 12 months later. Depression and anxiety early in the recovery period are independently associated with lower HRQoL. Identifying and managing these problems, ensuring adequate pain control and facilitating social functioning are key elements in improving HRQoL post-injury.

Ocular manifestations of X-linked dominant FAM58A mutation in toe syndactyly, telecanthus, anogenital, and renal malformations ('STAR') syndrome.

PURPOSE: To report the newest ophthalmic manifestations of a mother-daughter pair diagnosed with toe syndactyly, telecanthus, anogenital and renal malformations (STAR) syndrome, a rare X-linked developmental disorder. METHODS: The medical and ophthalmic records were reviewed for a mother-daughter pair diagnosed with FAM58A confirmed STAR syndrome on chromosome Xq28. RESULTS: The mother at birth had left foot syndactyly, telecanthus, anal stenosis, and clitoromegaly and was told at 19 she had a hypoplastic left kidney. The daughter, born at 38 weeks after a complication of oligohydramnios, had a more severe presentation, demonstrating toe syndactyly, telecanthus, anal stenosis, clitoromegaly, bilateral renal hypoplasia, ureteral reflux, urogenital sinus, and congenital heart disease amongst others. The pair shared similar ophthalmic findings, though those of the daughter were more pronounced. They included bilateral, medial upper eyelid prominences with madarosis, mild peripapillary atrophy, and soft macular drusen with the daughter also displaying optic nerve hypoplasia and peripheral anterior synechia in the iridocorneal angle. CONCLUSION: These ophthalmic findings are the first reported to our knowledge in association with STAR syndrome. The literature frequently demonstrates that patients with developmental anomalies often have ocular manifestations, warranting a full ophthalmic examination when the diagnosis of STAR syndrome has been made or is being considered.

The reduction rates of DEPC-modified mutant Thermus thermophilus Rieske proteins differ when there is a negative charge proximal to the cluster.

Rieske and Rieske-type proteins are electron transport proteins involved in key biological processes such as respiration, photosynthesis, and detoxification. They have a [2Fe-2S] cluster ligated by two cysteines and two histidines. A series of mutations, L135E, L135R, L135A, and Y158F, of the Rieske protein from Thermus thermophilus has been produced which probe the effects of the neighboring residues, in the second sphere, on the dynamics of cluster reduction and the reactivity of the ligating histidines. These properties were probed using titrations and modifications with diethyl pyrocarbonate (DEPC) at various pH values monitored using UV-Visible and circular dichroism spectrophotometry. These results, along with results from EPR studies, provide information on ligating histidine modification and rate of reduction of each of the mutant proteins. L135R, L135A, and Y158F react with DEPC similarly to wild type, resulting in modified protein with a reduced [2Fe-2S] cluster in <90 min, whereas L135E requires >15 h under the same conditions. Thus, the negative charge slows down the rate of reduction and provides an explanation as to why negatively charged residues are rarely, if ever, found in the equivalent position of other Rieske and Rieske-type proteins.

Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR.

Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5'-end triphosphate-a signature of certain viral and bacterial transcripts-confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe)in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity.

Changes in the sensory characteristics of mango cultivars during the production of mango purée and sorbet.

UNLABELLED: The effects of processing on the flavor and texture properties of 4 mango cultivars available in the U.S. were studied. Descriptive panelists evaluated fresh mango, mango purée, and mango sorbet prepared from each cultivar. Purées were made by pulverizing mango flesh, passing it through a china cap, and heating it to 85 °C for 15 s. To prepare the sorbets, purées were diluted with water (1:1), sucrose was added to increase the total soluble solids (TSS) to 32 ± 2 °Brix, and bases were frozen in a batch-type ice cream freezer. Processing fresh mangoes into mango purée generally decreased fruity character and mango identity and led to the appearance of a cooked note. Many of the flavor distinctions among cultivars carried over from fresh to purée samples, but much of the texture variation was lost. Thermal processing had differing effects on the flavor of the cultivars, and therefore, results suggest that mango cultivars for purées should be selected based on properties after thermal treatment. Processing purées into sorbets minimized flavor variation among cultivars, although Tommy Atkins sorbet was relatively high in green and green-viney character and low in caramelized flavor compared to the other cultivars in sorbet. Based on the current study only very distinct flavor properties of mango cultivars may carry over to sorbets. PRACTICAL APPLICATION: Findings from the present study will help mango purée and sorbet manufacturers select appropriate cultivars for their products by understanding the transformation that mango undergoes as it is processed into mango purée and subsequently to mango sorbet.

The human mitochondrial tRNAMet: structure/function relationship of a unique modification in the decoding of unconventional codons.

Human mitochondrial mRNAs utilize the universal AUG and the unconventional isoleucine AUA codons for methionine. In contrast to translation in the cytoplasm, human mitochondria use one tRNA, hmtRNA(Met)(CAU), to read AUG and AUA codons at both the peptidyl- (P-), and aminoacyl- (A-) sites of the ribosome. The hmtRNA(Met)(CAU) has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position 34 (f(5)C(34)), and a cytidine substituting for the invariant uridine at position 33 of the canonical U-turn in tRNAs. The structure of the tRNA anticodon stem and loop domain (hmtASL(Met)(CAU)), determined by NMR restrained molecular modeling, revealed how the f(5)C(34) modification facilitates the decoding of AUA at the P- and the A-sites. The f(5)C(34) defined a reduced conformational space for the nucleoside, in what appears to have restricted the conformational dynamics of the anticodon bases of the modified hmtASL(Met)(CAU). The hmtASL(Met)(CAU) exhibited a C-turn conformation that has some characteristics of the U-turn motif. Codon binding studies with both Escherichia coli and bovine mitochondrial ribosomes revealed that the f(5)C(34) facilitates AUA binding in the A-site and suggested that the modification favorably alters the ASL binding kinetics. Mitochondrial translation by many organisms, including humans, sometimes initiates with the universal isoleucine codons AUU and AUC. The f(5)C(34) enabled P-site codon binding to these normally isoleucine codons. Thus, the physicochemical properties of this one modification, f(5)C(34), expand codon recognition from the traditional AUG to the non-traditional, synonymous codons AUU and AUC as well as AUA, in the reassignment of universal codons in the mitochondria.

Analysis of the functional consequences of lethal mutations in mitochondrial translational elongation factors.

Mammalian mitochondria synthesize a set of thirteen proteins that are essential for energy generation via oxidative phosphorylation. The genes for all of the factors required for synthesis of the mitochondrially encoded proteins are located in the nuclear genome. A number of disease-causing mutations have been identified in these genes. In this manuscript, we have elucidated the mechanisms of translational failure for two disease states characterized by lethal mutations in mitochondrial elongation factor Ts (EF-Ts(mt)) and elongation factor Tu (EF-Tu(mt)). EF-Tu(mt) delivers the aminoacyl-tRNA (aa-tRNA) to the ribosome during the elongation phase of protein synthesis. EF-Ts(mt) regenerates EF-Tu(mt):GTP from EF-Tu(mt):GDP. A mutation of EF-Ts(mt) (R325W) leads to a two-fold reduction in its ability to stimulate the activity of EF-Tu(mt) in poly(U)-directed polypeptide chain elongation. This loss of activity is caused by a significant reduction in the ability of EF-Ts(mt) R325W to bind EF-Tu(mt), leading to a defect in nucleotide exchange. A mutation of Arg336 to Gln in EF-Tu(mt) causes infantile encephalopathy caused by defects in mitochondrial translation. EF-Tu(mt) R336Q is as active as the wild-type protein in polymerization using Escherichia coli 70S ribosomes and E. coli [(14)C]Phe-tRNA but is inactive in polymerization with mitochondrial [(14)C]Phe-tRNA and mitochondrial 55S ribosomes. The R336Q mutation causes a two-fold decrease in ternary complex formation with E. coli aa-tRNA but completely inactivates EF-Tu(mt) for binding to mitochondrial aa-tRNA. Clearly the R336Q mutation in EF-Tu(mt) has a far more drastic effect on its interaction with mitochondrial aa-tRNAs than bacterial aa-tRNAs.

Stereotactic radiosurgery for lung cancer.

Lung cancer is the most common cause of cancer death in both men and women in the United States. Anatomic lobectomy is the standard treatment and offers the best results for curative treatment of early stage non-small cell lung cancer (NSCLC). With an aging population, a significant proportion of patients are not surgical candidates at the time of diagnosis. In medically inoperable patients, standard external beam radiation has been offered as treatment, with suboptimal results. Stereotactic radiosurgery (SRS), a term coined by Leksell describes an approach using multiple convergent beams, precise localization with a stereotactic coordinate system, and rigid immobilization. It provides precise delivery of beams from multiple collimated paths which maximizes radiation delivery to the tumor, and minimizes the exposure of normal tissue. Early results with SRS are very encouraging, and prospective trials are underway in our institution and others to evaluate its role in early stage NSCLC. In article we review the role of stereotactic radiosurgery for the treatment of lung cancer.

Antibiotic effects on mitochondrial translation and in patients with mitochondrial translational defects.

The infantile presentation of mitochondrial respiratory chain defects frequently simulates acute bacterial infection and sepsis. Consequently, broad spectrum antibiotic therapy is often initiated before definitive diagnosis is reached and without taking into consideration the potential harm of antibiotics affecting mitochondrial translation. Here, we demonstrate that some commonly used translation-targeted antibiotics adversely affect the growth of fibroblasts from patients with defective mitochondrial translation systems. In addition, we show that these antibiotics inhibit mitochondrial translation in vitro. Our results suggest that patients with mitochondrial translation defects may be more vulnerable to toxic-side-effects following the administration of certain translation-targeted antibiotics.

Viral fitness implications of variation within an immunodominant CD8+ T-cell epitope of HIV-1.

Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness. Constructs recapitulating in vivo SL9-CTL escape variants showed markedly little effect on replication and fitness, as did non-natural conservative mutations targeting immunologically relevant positions of the epitope. Although certain residues of the epitope were constrained by viral requirements, our research reveals that there are multiple SL9 variants that are well tolerated virologically but fail to arise in vivo. In light of this data, assumptions regarding the balance of immune and viral selective pressures on this immunodominant epitope sequence need to be reassessed.