The utility of scoring systems in critically ill cirrhotic patients admitted to a general intensive care unit

Purpose: This study aimed to establish which prognostic scoring tool provides the greatest discriminative ability when assessing critically ill cirrhotic patients in a general intensive care unit (ICU) setting.<p></p> Methods: This was a 12-month, single-centered prospective cohort study performed in a general, nontransplant ICU. Forty clinical and demographic variables were collected on admission to calculate 8 prospective scoring tools. Patients were followed up to obtain ICU and inhospital mortality. Receiver operating characteristic curve analysis was used to determine the discriminative ability of the scores. Univariate and multivariate analyses were used to identify any independent predictors of mortality in these patients. The incorporation of any significant variables into the scoring tools was assessed.<p></p> Results: Fifty-nine cirrhotic patients were admitted over the study period, with an ICU mortality of 31%. All scores other than the renal-specific Acute Kidney Injury Network score had similar discriminative abilities, producing area under the curves of between 0.70 and 0.76. None reached the clinically applicable level of 0.8. The Sequential Organ Failure Assessment score was the best performing score. Lactate and ascites were individual predictors of ICU mortality with statistically significant odds ratios of 1.69 and 5.91, respectively. When lactate was incorporated into the Child-Pugh score, its prognostic accuracy increased to a clinically applicable level (area under the curve, 0.86).<p></p> Conclusions: This investigation suggests that established prognostic scoring systems should be used with caution when applied to the general, nontransplant ICU as compared to specialist centers. Our data suggest that serum arterial lactate may improve the prognostic ability of these scores

Social fragmentation, deprivation and urbanicity: relation to first-admission rates for psychoses

<i>Declaration</i> <i>of</i> <i>interest</i>: None. <i>Background</i>: Social disorganisation, fragmentation and isolation have long been posited as influencing the rate of psychoses at area level. Measuring such societal constructsis difficult. A census-based index measuring social fragmentation has been proposed. <i>Aims</i>: To investigate the association between first-admission rates for psychosis and area-based measures of social fragmentation, deprivation and urban/rural index. <i>Method</i>: We used indirect standardisation methods and logistic regression models to examine associations of social fragmentation, deprivation and urban/rural categories with first admissions for psychoses in Scotland for the 5-year period 1989–1993. <i>Results</i>: Areas characterised by high social fragmentation had higher first-ever admission rates for psychosis independent of deprivation and urban/rural status. There was a dose–response relationship between social fragmentation category and first-ever admission rates for psychosis. There was no statistically significant interaction between social fragmentation, deprivation and urban/rural index. <i>Conclusions</i>: First-admission rates are strongly associated with measures of social fragmentation, independent of material deprivation and urban/rural category

The Care Programme Approach and the end of indefinitely renewable Leave of Absence in Scotland

ObjectiveTo consider the relationship between the restriction of leave of absence (LOA) to 12 months, the introduction of community care orders (CCOs) and the implementation of the Care Programme Approach (CPA).DesignMultiple methods were employed: scrutiny of Mental Welfare Commission for Scotland (MWC) records; questionnaire to consultant psychiatrists and mental health officers (MHOs) regarding attitudes; survey of psychiatrists in respect of outcomes for named patients.SettingScotlandSubjectsTwo hundred and sixty six patients who were affected by the changes introduced by the Mental Health (Patients in the Community) Act 1995.ResultsInformation was available for 195 (73%) patients in relation to CPA. Of these 113 (58%) were included on CPA and for 63/113 (56%) (63/195 (32%)) CPA was considered to have enhanced patient care.Where CPA was considered useful it was because it was seen as bringing people together, enhancing the patient’s role in treatment and managing difficult situations. Negative comments regarding CPA were that it was unnecessary as the patient’s needs were straightforward, it duplicated current practices or it was too bureaucratic.ConclusionsDespite concerns expressed by professionals about the restriction to LOA and the guidance that patients should be on CPA, for only a minority of patients was CPA described as enhancing care. Questions are raised about the low use of CCOs and CPA by psychiatrists for patients who reached the new limits of LOA

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual im pairm ent. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessm ent of quality-of-life in the visually im paired and should support studies which evaluate the effectiveness of low vision rehabilitation services. © Copyright International Journal of Ophthalmology Press

Skeletal muscle stem cells express anti-apoptotic ErbB receptors during activation from quiescence

To be effective for tissue repair, satellite cells (the stem cells of adult muscle) must survive the initial activation from quiescence. Using an in vitro model of satellite cell activation, we show that erbB1, erbB2 and erbB3, members of the EGF receptor tyrosine kinase family, appear on satellite cells within 6 h of activation. We show that signalling via erbB2 provides an anti-apoptotic survival mechanism for satellite cells during the first 24 h, as they progress to a proliferative state. Inhibition of erbB2 signalling with AG825 reduced satellite cell numbers, concomitant with elevated caspase-8 activation and TUNEL labelling of apoptotic satellite cells. In serum-free conditions, satellite cell apoptosis could be largely prevented by a mixture of erbB1, erbB3 and erbB4 ligand growth factors, but not by neuregulin alone (erbB3/erbB4 ligand). Furthermore, using inhibitors specific to discrete intracellular signalling pathways, we identify MEK as a pro-apoptotic mediator, and the erbB-regulated factor STAT3 as an anti-apoptotic mediator during satellite cell activation. These results implicate erbB2 signalling in the preservation of a full compliment of satellite cells as they activate in the context of a damaged muscle

Germination response of common annual and perennial forbs to heat shock and smoke treatments in the Chaco Serrano, central Argentina

Fire is a key ecological factor affecting plant dynamics. In the last few decades, fire occurrence in the Chaco region has increased noticeably, challenging the adaptive capacity of plants to regenerate after a fire. Broad-leaved forb species have been much less studied than woody and graminoids, although they are an important component of fire dynamics. Here we analysed the germination response to heat shock of 70 and 110°C, smoke and their combination in 10 broad-leaved herbaceous species frequently occurring in the Chaco Serrano of Córdoba province, central Argentina, including five annual (Bidens subalternans, Conyza bonariensis, Schkuhria pinnata, Tagetes minuta and Zinnia peruviana) and five perennial species (Borreria eryngioides, Sida rhombifolia, Solidago chilensis, Taraxacum officinale and Verbena litoralis). We also compared the response of annual versus perennial species. Six species had highest germination when treated with heat and smoke combined, whereas two had lowest germination under this treatment, indicating synergistic and antagonistic interaction of these factors respectively. Most of the species tolerated heat shock (i.e. germination was similar to that in control treatment), whereas others had higher germination in response to heat shock, especially under the moderate 70°C treatment. Germination was higher than control (i.e. no heat and no smoke) after smoke treatment in four species. Perennial species showed higher average germination than annuals in both heat treatments and in the control. Annual species had higher average germination for all treatments involving smoke. The high variability observed at the species level, and the limited number of species studied calls for precaution in interpreting and extrapolating results. Nevertheless, our study shows a general positive response of both perennial and annual species to fire cues, suggesting an advantage of these species for colonizing post-fire environments, and being favoured under scenarios of increasingly frequent low-to-medium intensity fires.Fil: Arcamone, Julieta Rocío. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Diversidad Biológica y Ecológica. Cátedra de Ecología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Jaureguiberry, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin

Haplotype Analysis Improved Evidence for Candidate Genes for Intramuscular Fat Percentage from a Genome Wide Association Study of Cattle

In genome wide association studies (GWAS), haplotype analyses of SNP data are neglected in favour of single point analysis of associations. In a recent GWAS, we found that none of the known candidate genes for intramuscular fat (IMF) had been identified. In this study, data from the GWAS for these candidate genes were re-analysed as haplotypes. First, we confirmed that the methodology would find evidence for association between haplotypes in candidate genes of the calpain-calpastatin complex and musculus longissimus lumborum peak force (LLPF), because these genes had been confirmed through single point analysis in the GWAS. Then, for intramuscular fat percent (IMF), we found significant partial haplotype substitution effects for the genes ADIPOQ and CXCR4, as well as suggestive associations to the genes CEBPA, FASN, and CAPN1. Haplotypes for these genes explained 80% more of the phenotypic variance compared to the best single SNP. For some genes the analyses suggested that there was more than one causative mutation in some genes, or confirmed that some causative mutations are limited to particular subgroups of a species. Fitting the SNPs and their interactions simultaneously explained a similar amount of the phenotypic variance compared to haplotype analyses. Haplotype analysis is a neglected part of the suite of tools used to analyse GWAS data, would be a useful method to extract more information from these data sets, and may contribute to reducing the missing heritability problem

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype