Measuring newborn foot length to identify small babies in need of extra care: a cross sectional hospital based study with community follow-up in Tanzania

BACKGROUND\ud \ud Neonatal mortality because of low birth weight or prematurity remains high in many developing country settings. This research aimed to estimate the sensitivity and specificity, and the positive and negative predictive values of newborn foot length to identify babies who are low birth weight or premature and in need of extra care in a rural African setting.\ud \ud METHODS\ud \ud A cross-sectional study of newborn babies in hospital, with community follow-up on the fifth day of life, was carried out between 13 July and 16 October 2009 in southern Tanzania. Foot length, birth weight and gestational age were estimated on the first day and foot length remeasured on the fifth day of life.\ud \ud RESULTS\ud \ud In hospital 529 babies were recruited and measured within 24 hours of birth, 183 of whom were also followed-up at home on the fifth day. Day one foot length <7 cm at birth was 75% sensitive (95%CI 36-100) and 99% specific (95%CI 97-99) to identify very small babies (birth weight <1500 grams); foot length <8 cm had sensitivity and specificity of 87% (95%CI 79-94) and 60% (95%CI 55-64) to identify those with low birth weight (<2500 grams), and 93% (95%CI 82-99) and 58% (95%CI 53-62) to identify those born premature (<37 weeks). Mean foot length on the first day was 7.8 cm (standard deviation 0.47); the mean difference between first and fifth day foot lengths was 0.1 cm (standard deviation 0.3): foot length measured on or before the fifth day of life identified more than three-quarters of babies who were born low birth weight.\ud \ud CONCLUSION\ud \ud Measurement of newborn foot length for home births in resource poor settings has the potential to be used by birth attendants, community volunteers or parents as a screening tool to identify low birth weight or premature newborns in order that they can receive targeted interventions for improved survival

TOR and PKA Pathways Synergize at the Level of the Ste11 Transcription Factor to Prevent Mating and Meiosis in Fission Yeast

[Background]: In the fission yeast Schizosaccharomyces pombe, the TOR (target of rapamycin) and PKA (protein kinase A) signaling transduction pathways regulate the expression of genes required for cell growth and sexual differentiation in response to the nutritional environment. Inhibition of Tor2 signaling results in the induction of genes involved in sexual differentiation, and the cells undergo mating and meiosis, even under good nutritional conditions. The same phenotype is observed in mutants in which the PKA pathway is inactive. By contrast, Tor2 overexpression or mutations that hyperactivate PKA signaling impair sexual differentiation, even under poor nutritional conditions. Accordingly, a very important question is to understand the molecular mechanism by which these two pathways coordinately regulate gene expression in response to nutrients. [Methodology/Principal Findings]: Here we demonstrate that TOR and PKA pathways operate coordinately to negatively regulate sexual differentiation by inhibiting the nuclear accumulation of the Ste11 transcription factor. However, the Tor2 pathway is unable to block the nuclear localization of Ste11 under good nutritional conditions when the PKA pathway is inactive. Using microarray analyses, we found that both pathways inhibit sexual differentiation by blocking ste11-dependent gene expression. [Conclusions/Significance]: We conclude that both the PKA and the TOR pathways inhibit Ste11 nuclear accumulation to repress Ste11-dependent gene expression. However, the PKA pathway plays a quantitatively more important role than the TOR pathway in this process.N.V. is supported by a postdoctoral grant from the Carlos III Institute, Ministerio de Sanidad. Our group is supported by grants from la Junta de Castilla y Leon (Grupo de Excelencia grant GR265) and the Spanish Ministry of Science and Innovation (BFU2008-01808 and Consolider Ingenio CSD2007-00015).Peer reviewe

Oncolytic Adenoviruses Armed with Thymidine Kinase Can Be Traced by PET Imaging and Show Potent Antitumoural Effects by Ganciclovir Dosing

Replication-competent adenoviruses armed with thymidine kinase (TK) combine the concepts of virotherapy and suicide gene therapy. Moreover TK-activity can be detected by noninvasive positron emission-computed tomography (PET) imaging, what could potentially facilitate virus monitoring in vivo. Here, we report the generation of a novel oncolytic adenovirus that incorporates the Tat8-TK gene under the control of the Major Late Promoter in a highly selective backbone thus providing selectivity by targeting the retinoblastoma pathway. The selective oncolytic TK virus, termed ICOVIR5-TK-L, showed reduced potency compared to a non-selective counterpart. However the combination of ICOVIR5-TK-L with ganciclovir (GCV) induced a potent antitumoural effect similar to that of wild type adenovirus in a preclinical model of pancreatic cancer. Although the treatment with GCV provoked a reduction in the viral yield, both in vitro and in vivo, a two-cycle treatment of virus and GCV resulted in an enhanced antitumoral response that correlated with high TK-activity, based on microPET measurements. Thus, TK-expressing oncolytic adenoviruses can be traced by PET imaging providing real time information on the activity of the virus and its antitumoral potency can be optimized by GCV dosing

Redundant Mechanisms Prevent Mitotic Entry Following Replication Arrest in the Absence of Cdc25 Hyper-Phosphorylation in Fission Yeast

Following replication arrest the Cdc25 phosphatase is phosphorylated and inhibited by Cds1. It has previously been reported that expressing Cdc25 where 9 putative amino-terminal Cds1 phosphorylation sites have been substituted to alanine results in bypass of the DNA replication checkpoint. However, these results were acquired by expression of the phosphorylation mutant using a multicopy expression vector in a genetic background where the DNA replication checkpoint is intact. In order to clarify these results we constructed a Cdc25(9A)-GFP native promoter integrant and examined its effect on the replication checkpoint at endogenous expression levels. In this strain the replication checkpoint operates normally, conditional on the presence of the Mik1 kinase. In response to replication arrest the Cdc25(9A)-GFP protein is degraded, suggesting the presence of a backup mechanism to eliminate the phosphatase when it cannot be inhibited through phosphorylation

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Effet d\'une alimentation à base d\'épluchures et de feuilles de manioc sur les performances zootechniques et économiques du lapin

Soixante quinze (75) lapereaux sevrés à 35 jours ont été répartis au hasard sous 5 traitements à 3 répétitions de telle sorte que chaque répétition comporte 5 lapereaux. Les cinq rations R0, R1, R2, R3 et R4 contenant respectivement 0, 10, 20, et 30 % d\'épluchures de manioc et une combinaison de 10 et 20 % respectivement de feuilles et d\'épluchures de racine de manioc. Après une période expérimentale de 8 semaines, les paramètres zootechniques ont été significativement influencés (p< 0,05) par les différentes rations testées. A la fin de l\'expérience, le gain de poids moyen quotidien et la consommation alimentaire moyenne journalière les plus élevés (26,49 et 78,74 g/j) ont été obtenus sous la ration R4. Quant aux indices de consommation, les plus faibles on été enregistrés sous la ration R3 (2,29). La ration R4 a permis de produire le kilogramme de poids vif et un aliment à moindre coût soit respectivement 1139,03 F CFA et 57,28 FCFA .Seventy-five (75) young rabbits weaned at 35 days were randomly distributed over 5 treatments of 3 repetitions, so that each repetition comprises 5 young rabbits. The five feeds R0, R1, R2, R3 and R4 respectively contained 0, 10, 20, and 30 % of cassava peels and a combination of respectively 10 and 20 % of leaves and cassava peels. After a 8 weeks experimental period, the results of the parameters considered in this experiment were as follows: the zootechnical parameters were significantly influenced (