Mental health and employment outcomes in working-age US adults, 2010-2019.

BACKGROUND: Individuals with severe mental illness experience greater unemployment and barriers to workforce re-entry. However, less is known about additional indicators of employment stability for individuals across mental illness severity. AIMS: This study aims to examine associations between mental illness severity, use and adequacy of mental health treatment, and indicators of employment stability. METHODS: In this repeated cross-sectional study, 2010-2019 data from the U.S. National Survey of Drug Use and Health were used to construct multivariate logistic regression models predicting the odds of part-time employment, past-year work interruption, number of past-year employers, and past-month health-related work absence by mental illness severity and adequacy of mental health treatment. RESULTS: Compared to individuals with no mental illness, those with any and severe mental illness had significantly higher odds of part-time employment (adjusted odds ratios [AORs] = 1.51 and 2.16, 95% confidence intervals [CIs] 1.4-1.6 and 2.0-2.3), multiple past-year employers (AORs = 1.78 and 2.34, CIs 1.7-1.9 and 2.1-2.6), past-year work interruption (AORs = 1.69 and 2.20, CIs 1.6-1.8 and 2.1-2.4), and >7 days of past-month work absence (AORs = 2.51 and 3.82, CIs 2.3-2.8 and 3.3-4.5). Among respondents with mental illness, perceived inadequacy of mental treatment predicted higher odds of all adverse employment outcomes. CONCLUSIONS: Compared to those with no mental illness, individuals with mental illness of any severity have higher odds of employment instability. Policy and programmatic support aimed at addressing the needs of individuals with mental illness, including access to adequate mental health treatment, are needed to facilitate continued, competitive employment.

Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

Effects of publication bias on conservation planning.

Conservation planners need reliable information on spatial patterns of biodiversity. However, existing data sets are skewed because some ecosystems, taxa, and locations are underrepresented. We determined how many articles have been published in recent decades on the biodiversity of different countries and their constituent provinces. We searched the Web of Science catalogues Science Citation Index (SCI) and Social Science Citation Index (SSCI) for biodiversity-related articles published from 1993 to 2016 that included country and province names. We combined data on research publication frequency with other provincial-scale factors hypothesized to affect the likelihood of research activity (i.e., economic development, human presence, infrastructure, and remoteness). Areas that appeared understudied relative to the biodiversity expected based on site climate likely have been inaccessible to researchers for reasons, notably armed conflict. Geographic publication bias is of most concern in the most remote areas of sub-Saharan Africa and South America. Our provincial-scale model may help compensate for publication biases in conservation planning by revealing the spatial extent of research needs and the low cost of redoing this analysis annually.

Efectos del Sesgo de Publicación sobre la Planeación de la Conservación Resumen Los planeadores de la conservación necesitan información confiable sobre los patrones espaciales de la biodiversidad. Sin embargo, los conjuntos de datos existentes están distorsionados porque algunos ecosistemas, taxones y localidades están subrepresentados. Determinamos cuántos artículos sobre la biodiversidad de diferentes países y sus provincias constituyentes han sido publicados en décadas recientes. Buscamos artículos relacionados con la biodiversidad publicados entre 1993 y 2016 que incluyeran el nombre de países y provincias en los catálogos SCI y SSCI de la Web of Science. Combinamos los datos de frecuencia de publicación de investigaciones con otros factores de escala provincial que creemos afectarían la probabilidad de la actividad de investigación (es decir, desarrollo económico, presencia humana, infraestructura y lejanía). Las áreas que aparentaron estar poco estudiadas en relación con la biodiversidad esperada basada en el clima del sitio probablemente han estado inaccesibles para los investigadores por diferentes razones, notablemente los conflictos armados. El sesgo geográfico en las publicaciones es un tema de importancia para las áreas más remotas del África subsahariana y América del Sur. Nuestro modelo de escala provincial puede ayudar a compensar los sesgos de publicación en la planeación de la conservación al revelar la extensión espacial de las necesidades de investigación y los bajos costos de repetir este análisis cada año.

Electronic Prompts Can Reduce The Number Of Unnecessary Clotting Screens Ordered For Patients.

In an attempt to reduce the number of inappropriate clotting screens being performed in our Trust, an electronic prompt was introduced to our haematology requesting system. Over the six month period after introduction of this prompt the number of clotting screen requests reduced by 7001, representing a 21% reduction when compared to the same 6 month period one year earlier. This represented a cost saving of over £98,000 without any increase in adverse incidents being reported related to bleeding complications.

The C-terminal tail of tetraspanin proteins regulates their intracellular distribution in the parasite Trichomonas vaginalis.

The parasite Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection. Here, we report the cellular analysis of T.vaginalis tetraspanin family (TvTSPs). This family of membrane proteins has been implicated in cell adhesion, migration and proliferation in vertebrates. We found that the expression of several members of the family is up-regulated upon contact with vaginal ectocervical cells. We demonstrate that most TvTSPs are localized on the surface and intracellular vesicles and that the C-terminal intracellular tails of surface TvTSPs are necessary for proper localization. Analyses of full-length TvTSP8 and a mutant that lacks the C-terminal tail indicates that surface-localized TvTSP8 is involved in parasite aggregation, suggesting a role for this protein in parasite : parasite interaction.

Diagnostic and mechanistic implications of serum free light chains, albumin and alpha-fetoprotein in hepatocellular carcinoma.

BACKGROUND: Mass spectroscopy analysis suggested low serum albumin and high immunoglobulin free light chain (sFLC) levels may have diagnostic value in hepatocellular carcinoma (HCC). Our aims were to apply quantitative assays to confirm these observations, determine their diagnostic utility, and investigate the mechanisms involved. METHODS: Albumin, sFLC, routine liver and renal function tests were measured in patients with chronic liver disease with (n=102) and without (n=113) HCC. The discriminant performance was compared with the current standard serological test alpha-fetoprotein (AFP) using receiver operating characteristic (ROC) and area under the curve (AUC) analyses. RESULTS: sFLC and serum albumin were each confirmed to have discriminatory utility in HCC with AUC values of 0.7 and 0.8, respectively. sFLC were strongly correlated with gammaglobulin levels and both these were inversely related to serum albumin levels. The discriminatory utility of sFLC was retained after adjusting for renal and liver function. CONCLUSIONS: Serum levels of sFLC and albumin were strongly associated with HCC as predicted by mass spectroscopy. Discrimination of HCC by AFP was improved by the addition of either albumin or sFLC. Larger prospective studies are required to determine how AFP, sFLC and albumin might be combined in a useful diagnostic approach for HCC.

Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.

BACKGROUND: The Japanese 'BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients. METHODS: In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance. RESULTS: The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival. CONCLUSIONS: The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts.

Sorafenib for advanced hepatocellular carcinoma (HCC): impact of rationing in the United Kingdom.

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) is dependent upon tumour stage, performance status (PS), severity of underlying liver disease, and the availability of appropriate therapies. The unavailability of sorafenib may have a significantly adverse effect on the prognosis of UK patients with advanced HCC. During the study period, access to sorafenib was at the discretion of local health funding bodies, a process that may delay or deny access to the drug and that remains in place for Wales, Scotland, and Northern Ireland. Here, we attempt to address the impact of this system on patients with advanced HCC in the United Kingdom. METHODS: This is a retrospective study performed in the two largest specialist hepatobiliary oncology units in the United Kingdom. Funding applications were made to local funding bodies for patients with advanced HCC for whom sorafenib was considered appropriate (advanced HCC not suitable for loco-regional therapies, compensated chronic liver disease, PS 0-2). RESULTS: A total of 133 applications were made, of which 57 (43%) were approved and 76 (57%) declined. Demographics and prognostic factors were balanced between the two groups. This cohort had a number of adverse prognostic features: patients were predominantly PS 1-2; the majority had multifocal disease with the largest lesion being >5 cm; and macroscopic vascular invasion, metastases, and AFP >,000 ng ml(-1), were each present in one-third of cases. The median time from application to funding decision was 17 days (range 3-260 days). For the primary 'intention-to-treat' analysis, median overall survival was 4.1 months when funding was declined, and 9.5 months when funding was approved (hazard ratio (HR) 0.48; 95% CI 0.3186-0.7267; P=0.0005). CONCLUSION: These data support the use of sorafenib for patients with advanced HCC as an effective intervention. In the United Kingdom, this applies to a relatively small group of patients, estimated to total ∼800 per year who, unfortunately, do not survive long enough to themselves lobby for the availability of this drug. These data provide a comparison of sorafenib with supportive care and demonstrate the potential detrimental impact on patient outcomes of rationing health-care resources on the basis of cost.

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma.

BACKGROUND: Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer. METHODS: We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients. RESULTS: Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion. CONCLUSIONS: This 'dual-omic' strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.

Fewer invited talks by women in evolutionary biology symposia.

Lower visibility of female scientists, compared to male scientists, is a potential reason for the under-representation of women among senior academic ranks. Visibility in the scientific community stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under-represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001-2011, 9-23% of invited speakers were women. This under-representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high-impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early-mid career stage scientists, but was similar to senior scientists and authors that have published in high-impact journals. High-quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks.

Macrophage migration inhibitory factor and DJ-1 in gastric cancer: differences between high-incidence and low-incidence areas.

BACKGROUND: There is a need for sensitive and specific blood-borne markers for the detection of gastric cancer. Raised serum macrophage inhibitory factor (MIF) levels have been proposed as a marker for gastric cancer diagnosis but, to date, studies have only encompassed patients from high-incidence areas. METHODS: We have compared the serum concentration of MIF in a large cohort of UK and Japanese gastric cancer patients, together with appropriate control subjects (age and gender matched). Carcinoembryonic antigen and H. pylori IgG were also measured, as was DJ-1, a novel candidate protein biomarker identified by analysis of gastric cancer cell line secretomes. RESULTS: Marked elevations of the serum concentration of MIF and DJ-1 were seen in Japanese patients with gastric cancer compared with Japanese controls, a trend not seen in the UK cohort. These results could not be accounted for by differences in age, disease stage or H. pylori status. CONCLUSION: In regions of high, but not low incidence of gastric cancer, both MIF and DJ-1 have elevated serum concentrations in gastric cancer patients, compared with controls. This suggests that differing mechanisms of disease pathogenesis may be at play in high- and low-incidence regions.

Severe bilaterally symmetrical alopecia in a horse.

A 9-year-old Tennessee Walking Horse gelding was presented for diagnosis of the cause of extensive alopecia. Complete hair loss was noted over the head, neck, shoulder, thigh, and proximal limbs, but the trunk, distal limbs, pelvic area, mane, and tail were unaffected. The alopecic areas were visually noninflammatory with no exudate or crust except on the shoulder and along the back, where multifocal patchy areas of alopecia with scales and crust were evident. The horse was slightly pruritic. Microscopically, the hair bulbs, inner and outer root sheaths of inferior segments, and perifollicular regions were infiltrated by small to moderate numbers of small lymphocytes. Similar inflammation was occasionally evident in isthmus follicular walls as well as some apocrine glands. No sebaceous glands were affected. Immunohistochemistry confirmed that the small lymphocytes were CD3(+) T lymphocytes. The epidermis from the skin with scale and crusts along the horse's back exhibited mild to moderate hyperplasia, mild lymphocytic exocytosis, mild eosinophilic dermatitis, and diffuse parakeratosis with numerous budding yeasts, consistent with Malassezia spp. The final disease diagnosis was made as alopecia areata with Malassezia dermatitis. Alopecia areata could be a contributing underlying factor for Malassezia dermatitis.

Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis.

REASONS FOR PERFORMING STUDY: There is a need to assess the laminar inflammatory response in a laminitis model that more closely resembles clinical cases of sepsis-related laminitis than the black walnut extract (BWE) model. OBJECTIVES: To determine if a similar pattern of laminar inflammation, characterised by proinflammatory cytokine expression, occurs in the CHO model of laminitis as has been previously reported for the BWE model. METHODS: Sixteen horses administered 17.6 g of starch (85% corn starch/15% wood flour)/kg bwt via nasogastric (NG) tube were anaesthetised either after developing a temperature>38.9°C (DEV group, n=8) or at onset of Obel grade 1 lameness (OG1 group, n=8). Control horses (CON group, n=8) were anaesthetised 24 h after NG administration of 6 l of deionised water. Laminar tissue was collected from horses while under anaesthesia, followed by humane euthanasia. Real time-quantitative PCR was used to assess laminar mRNA concentrations of genes involved in inflammatory signalling. RESULTS: Increased mRNA concentrations (P<0.05) for IL-1ß, IL-6, IL-12p35, COX-2, E-selectin and ICAM-1 were present in laminae from horses with OG1 lameness but not at the DEV time, when compared to the CON horses. No differences between the groups were found for IL-2, IL-4, IL-10, TNF-α, IFN-γ or COX-1 at either the DEV or OG1 time points. CONCLUSIONS: There was a notable difference in the temporal pattern of inflammatory events between the BWE and CHO models, with the majority of laminar inflammatory events appearing to occur at or near the onset of lameness in the CHO model, whereas many of these events peak earlier in the developmental stages in the BWE model. This suggests that, in addition to circulating inflammatory molecules, there may be a local phenomenon in the CHO model resulting in the simultaneous onset of multiple laminar events including endothelial activation, leucocyte emigration and proinflammatory cytokine expression. POTENTIAL RELEVANCE: The similar (although somewhat delayed) inflammatory response in the CHO model of laminitis indicates that inflammatory signalling is a consistent entity in the pathophysiology of laminitis.

Does organic farming benefit farmland birds in winter?

The generally higher biodiversity on organic farms may be influenced by management features such as no synthetic pesticide and fertilizer inputs and/or by differences in uncropped habitat at the site and landscape scale. We analysed bird and habitat data collected on 48 paired organic and conventional farms over two winters to determine the extent to which broad-scale habitat differences between systems could explain overall differences in farmland bird abundance. Density was significantly higher on organic farms for six out of 16 species, and none on conventional. Total abundance of all species combined was higher on organic farms in both years. Analyses using an information-theoretic approach suggested that both habitat extent and farm type were important predictors only for starling and greenfinch. Organic farming as currently practised may not provide significant benefits to those bird species that are limited by winter food resources, in particular, several declining granivores.

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1-3 as potential biomarkers for gastric cancer.

BACKGROUND: Proteomic methods have the potential to meet the urgent need for better cancer biomarkers. We have used a range of proteomic analyses of serum and tissue from gastric cancer patients and relevant controls to discover biomarkers for gastric cancer. METHODS: Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI) and antibody arrays were used to compare protein expression in 21 pairs of gastric cancer tissue and adjacent normal mucosa and serum from 51 gastric cancer patients and 29 patients with benign gastric diseases. Expression differences were confirmed by enzyme-linked immunosorbent assay. RESULTS: Tissue analysis shows human neutrophil peptides 1-3 (HNPs 1-3) elevated 10-fold (P=0.001) in gastric cancer relative to adjacent normal mucosa. Macrophage migration inhibitory factor (MIF) was increased five-fold (P=1.84 x 10(-7)) in the serum of gastric cancer patients relative to individuals with benign gastric disease. The large increase in MIF concentration in serum gives an area under the receiver operating characteristic curve of 0.85. CONCLUSIONS: Proteomic analyses of serum and tissue indicate that HNPs 1-3 and MIF have potential as biomarkers for gastric cancer. In particular MIF may be useful, either alone or in combination with other markers, for diagnosing and monitoring gastric cancer.

Fast targeted multidimensional NMR metabolomics of colorectal cancer.

The study of small molecules in body fluids has become an important tool to monitor the state of biological organisms. Applications range from model studies using cell lines to applications where human body fluids are used to monitor disease states or drug responses. NMR spectroscopy has been an important tool for metabolomics although severe overlap of signals has limited the number of compounds, which can be unambiguously identified and quantified. Therefore, deconvolution of NMR spectra is one of the greatest challenges for NMR-based metabolomics. This has commonly been achieved by using multidimensional spectra that have the disadvantage of requiring significantly longer acquisition times. Recently, a number of methods have been described to record NMR spectra much faster. Here, we explore the use of Hadamard-encoded TOCSY spectra to simultaneously select multiple lines from crowded NMR spectra of blood serum samples to acquire pseudo-two-dimensional spectra in minutes which would otherwise require many hours. The potential of this approach is demonstrated for the detection of a signature for colorectal cancer from human blood samples.

Multicentre validation of a clinical prognostic score integrating the systemic inflammatory response to the host for patients treated with curative-intent for colorectal liver metastases: The Liverpool score.

BACKGROUND: This study aimed to create a new prognostic score integrating the systemic inflammatory response to predict survival in patients treated with curative intent for colorectal liver metastases (CLM). METHODS: We identified independent prognostic factors in patients who underwent liver surgery for CLM in a tertiary centre in the United Kingdom (UK) between 2010 and 2015. A pre- and a postoperative score (Liverpool score) were created by combining these factors to stratify patients into different risk groups. These new scores were validated in an international cohort of 219 patients from China and France. RESULTS: Multivariate cox regression analysis of the 364 patients of the UK cohort identified 6 preoperative and 1 postoperative prognostic factors for overall survival (OS): American society of anaesthesiologists (ASA) score, location and node status of the primary tumour, number and size of CLM, neutrophil-to-lymphocyte ratio (NLR) and resection margin. Both pre- and postoperative scores can be calculated with an online calculator at https://jscalc.io/calc/PXatrmjfrEFpYy2t. Using the pre-operative model on the UK cohort, median OS was 61.22 (50.23, not reached) months in the low-risk group (n = 162) and 30.36 (23.68, 35.95) months in the high-risk group (n = 162, p < 0.0001). The same difference was observed in the validation cohort. The Liverpool score outperformed previously published scoring system with a c-index of 0.619 pre-operatively and of 0.637 post-operatively. CONCLUSION: We developed a new prognostic score based on clinicopathologic characteristics including the site of the primary tumour location and on measurement of the systemic inflammatory response which could help to tailor patients' management.

Trends in ixodid tick abundance and distribution in Great Britain.

The popular, but rarely documented, view in Britain is that ticks have increased in distribution and abundance over recent years. To assess this, we gathered evidence for changes in tick distribution and abundance by distributing a survey questionnaire throughout Britain and by analysing trends in the prevalence of tick infestation on red grouse chicks Lagopus lagopus scoticus Latham (Galliformes: Tetranoidae), gathered over 19 years at three Scottish sites, and on deer (Cetartiodactyla: Cervidae) culled over 11 years on 26 Ministry of Defence (MoD) estates. Based on the survey, the current known distribution of Ixodes ricinus Linnaeus (Acari: Ixodidae) has expanded by 17% in comparison with the previously known distribution. The survey indicated that people perceive there to be more ticks today than in the past at 73% of locations throughout Britain. Reported increases in tick numbers coincided spatially with perceived increases in deer numbers. At locations where both tick and deer numbers were reported to have increased, these perceived changes occurred at similar times, raising the possibility of a causal link. At other locations, tick numbers were perceived to have increased despite reported declines in deer numbers. The perceptions revealed by the survey were corroborated by quantitative data from red grouse chicks and culled deer. Tick infestation prevalence increased over time on all grouse moors and 77% of MoD estates and decreased at six locations.

Pharmacokinetics of intravenous lithium chloride and assessment of agreement between two methods of lithium concentration measurement in the horse.

BACKGROUND: Pharmacokinetics of lithium chloride (LiCl) administered as a bolus, once i.v. have not been determined in horses. There is no point-of-care test to measure lithium (Li+ ) concentrations in horses in order to monitor therapeutic levels and avoid toxicity. OBJECTIVES: To determine the pharmacokinetics of LiCl in healthy adult horses and to compare agreement between two methods of plasma Li+ concentration measurement: spectrophotometric enzymatic assay (SEA) and inductively coupled plasma mass spectrometry (ICP-MS). STUDY DESIGN: Nonrandomised, single exposure with repeated measures over time. METHODS: Lithium chloride was administered (0.15 mmol/kg bwt) as an i.v. bolus to eight healthy adult horses. Blood samples were collected pre-administration and at multiple times until 48 h post-administration. Samples were analysed by two methods (SEA and ICP-MS) to determine plasma Li+ concentrations. Pharmacokinetics were determined based on the reference ICP-MS data. RESULTS: Adverse side effects were not observed. The SEA showed linearity, R2 = 0.9752; intraday coefficient of variation, 2.5%; and recovery, 96.3%. Both noncompartmental and compartmental analyses (traditional two-stage and nonlinear mixed-effects [NLME] modelling) were performed. Geometric mean values of noncompartmental parameters were plasma Li+ concentration at time zero, 2.19 mmol/L; terminal elimination half-life, 25.68 h; area under the plasma concentration-time curve from time zero to the limit of quantification, 550 mmol/L min; clearance, 0.273 mL/min/kg; mean residence time, 31.22 h; and volume of distribution at steady state, 511 mL/kg. Results of the traditional two-stage analysis showed good agreement with the NLME modelling approach. Bland-Altman analyses demonstrated poor agreement between the SEA and ICP-MS methods (95% limits of agreement = 0.14 ± 0.13 mmol/L). MAIN LIMITATIONS: Clinical effects of LiCl have not been investigated. CONCLUSIONS: The LiCl i.v. bolus displayed pharmacokinetics similar to those reported in other species. The SEA displayed acceptable precision but did not agree well with the reference method (ICP-MS). The Summary is available in Spanish - see Supporting Information.

Analysis of a ubiquitous promoter element in a primitive eukaryote: early evolution of the initiator element.

Typical metazoan core promoter elements, such as TATA boxes and Inr motifs, have yet to be identified in early-evolving eukaryotes, underscoring the extensive divergence of these organisms. Towards the identification of core promoters in protists, we have studied transcription of protein-encoding genes in one of the earliest-diverging lineages of Eukaryota, that represented by the parasitic protist Trichomonas vaginalis. A highly conserved element, comprised of a motif similar to a metazoan initiator (Inr) element, surrounds the start site of transcription in all examined T. vaginalis genes. In contrast, a metazoan-like TATA element appears to be absent in trichomonad promoters. We demonstrate that the conserved motif found in T. vaginalis protein-encoding genes is an Inr promoter element. This trichomonad Inr is essential for transcription, responsible for accurate start site selection, and interchangeable between genes, demonstrating its role as a core promoter element. The sequence requirements of the trichomonad Inr are similar to metazoan Inrs and can be replaced by a mammalian Inr. These studies show that the Inr is a ubiquitous, core promoter element for protein-encoding genes in an early-evolving eukaryote. Functional and structural similarities between this protist Inr and the metazoan Inr strongly indicate that the Inr promoter element evolved early in eukaryotic evolution.