Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra

The authors of this study developed the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR–FTIR) combined with machine learning as a point-of-care (POC) diagnostic platform, considering neonatal respiratory distress syndrome (nRDS), for which no POC currently exists, as an example. nRDS can be diagnosed by a ratio of less than 2.2 of two nRDS biomarkers, lecithin and sphingomyelin (L/S ratio), and in this study, ATR–FTIR spectra were recorded from L/S ratios of between 1.0 and 3.4, which were generated using purified reagents. The calibration of principal component (PCR) and partial least squares (PLSR) regression models was performed using 155 raw baselined and second derivative spectra prior to predicting the concentration of a further 104 spectra. A three-factor PLSR model of second derivative spectra best predicted L/S ratios across the full range (R2: 0.967; MSE: 0.014). The L/S ratios from 1.0 to 3.4 were predicted with a prediction interval of +0.29, −0.37 when using a second derivative spectra PLSR model and had a mean prediction interval of +0.26, −0.34 around the L/S 2.2 region. These results support the validity of combining ATR–FTIR with machine learning to develop a point-of-care device for detecting and quantifying any biomarker with an interpretable mid-infrared spectrum

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Audio versus written feedback: exploring learners’ preference and the impact of feedback format on students’ academic performance

Very little is known about the impact of the different types of feedback on students’ academic performance. This paper explores students’ preference in the use of audio and written feedback and how each type of feedback received by students impact on their academic performance in subsequent assignments. The study involved 68 students who were divided into two groups that received either audio or written feedback in their first assignment which was then recalled and applied into the second assignment. An analysis of results obtained in the second assignment was conducted and comparisons made between students in the audio and written feedback group. Students were also surveyed using an online questionnaire to ascertain their perceptions about the type of feedback they had received. The study established that the type of feedback received did not impact on students’ grades in the subsequent assignment. In addition, while students were broadly positive about audio feedback, they indicated a strong preference for written feedback in future assignments. The study recommends, among other things, further investigation into the link between students’ learning styles and their preferences for different types of feedback

Experiences, Opportunities and Challenges of Implementing Task Shifting in Underserved Remote Settings: The Case of Kongwa District, Central Tanzania.

Tanzania is experiencing acute shortages of Health Workers (HWs), a situation which has forced health managers, especially in the underserved districts, to hastily cope with health workers' shortages by adopting task shifting. This has however been due to limited options for dealing with the crisis of health personnel. There are on-going discussions in the country on whether to scale up task shifting as one of the strategies for addressing health personnel crisis. However, these discussions are not backed up by rigorous scientific evidence. The aim of this paper is two-fold. Firstly, to describe the current situation of implementing task shifting in the context of acute shortages of health workers and, secondly, to provide a descriptive account of the potential opportunities or benefits and the likely challenges which might ensue as a result of implementing task shifting. We employed in-depth interviews with informants at the district level and supplemented the information with additional interviews with informants at the national level. Interviews focussed on the informants' practical experiences of implementing task shifting in their respective health facilities (district level) and their opinions regarding opportunities and challenges which might be associated with implementation of task shifting practices. At the national level, the main focus was on policy issues related to management of health personnel in the context of implementation of task shifting, in addition to seeking their opinions and perceptions regarding opportunities and challenges of implementing task shifting if formally adopted. Task shifting has been in practice for many years in Tanzania and has been perceived as an inevitable coping mechanism due to limited options for addressing health personnel shortages in the country. Majority of informants had the concern that quality of services is likely to be affected if appropriate policy infrastructures are not in place before formalising tasks shifting. There was also a perception that implementation of task shifting has ensured access to services especially in underserved remote areas. Professional discontent and challenges related to the management of health personnel policies were also perceived as important issues to consider when implementing task shifting practices. Additional resources for additional training and supervisory tasks were also considered important in the implementation of task shifting in order to make it deliver much the same way as it is for conventional modalities of delivering care. Task shifting implementation occurs as an ad hoc coping mechanism to the existing shortages of health workers in many undeserved areas of the country, not just in the study site whose findings are reported in this paper. It is recommended that the most important thing to do now is not to determine whether task shifting is possible or effective but to define the limits of task shifting so as to reach a consensus on where it can have the strongest and most sustainable impact in the delivery of quality health services. Any action towards this end needs to be evidence-based

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Using Electronic Technology to Improve Clinical Care -- Results from a Before-after Cluster Trial to Evaluate Assessment and Classification of Sick Children According to Integrated Management of Childhood Illness (IMCI) Protocol in Tanzania.

Poor adherence to the Integrated Management of Childhood Illness (IMCI) protocol reduces the potential impact on under-five morbidity and mortality. Electronic technology could improve adherence; however there are few studies demonstrating the benefits of such technology in a resource-poor settings. This study estimates the impact of electronic technology on adherence to the IMCI protocols as compared to the current paper-based protocols in Tanzania. In four districts in Tanzania, 18 clinics were randomly selected for inclusion. At each site, observers documented critical parts of the clinical assessment of children aged 2 months to 5 years. The first set of observations occurred during examination of children using paper-based IMCI (pIMCI) and the next set of observations occurred during examination using the electronic IMCI (eIMCI). Children were re-examined by an IMCI expert and the diagnoses were compared. A total of 1221 children (671 paper, 550 electronic) were observed. For all ten critical IMCI items included in both systems, adherence to the protocol was greater for eIMCI than for pIMCI. The proportion assessed under pIMCI ranged from 61% to 98% compared to 92% to 100% under eIMCI (p < 0.05 for each of the ten assessment items). Use of electronic systems improved the completeness of assessment of children with acute illness in Tanzania. With the before-after nature of the design, potential for temporal confounding is the primary limitation. However, the data collection for both phases occurred over a short period (one month) and so temporal confounding was expected to be minimal. The results suggest that the use of electronic IMCI protocols can improve the completeness and consistency of clinical assessments and future studies will examine the long-term health and health systems impact of eIMCI

'The Germans are Hydrophobes': Germany and the Germans in the Shaping of French Identity

This article addresses issues of national identity and nationalism in the age of the French Revolution by looking at French attitudes towards the Germans. It engages with theories of nationalism while presenting empirical evidence gleaned from archival research. This material, sometimes grimly, sometimes rather amusingly, reveals much about French ideas and prejudices about the Germans and how it reflected back on the revolutionary and Napoleonic sense of what it meant to be French

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Relative Effectiveness of Mating Success and Sperm Competition at Eliminating Deleterious Mutations in Drosophila melanogaster

Condition-dependence theory predicts that sexual selection will facilitate adaptation by selecting against deleterious mutations that affect the expression of sexually selected traits indirectly via condition. Recent empirical studies have provided support for this prediction; however, their results do not elucidate the relative effects of pre- and postcopulatory sexual selection on deleterious mutations. We used the Drosophila melanogaster model system to discern the relative contributions of pre- and postcopulatory processes to selection against deleterious mutations. To assess second-male ejaculate competition success (P2; measured as the proportion of offspring attributable to the experimental male) and mating success, mutant and wild-type male D. melanogaster were given the opportunity to mate with females that were previously mated to a standard competitor male. This process was repeated for males subjected to a diet quality manipulation to test for effects of environmentally-manipulated condition on P2 and mating success. While none of the tested mutations affected P2, there was a clear effect of condition. Conversely, several of the mutations affected mating success, while condition showed no effect. Our results suggest that precopulatory selection may be more effective than postcopulatory selection at removing deleterious mutations. The opposite result obtained for our diet manipulation points to an interesting discrepancy between environmental and genetic manipulations of condition, which may be explained by the multidimensionality of condition. Establishing whether the various stages of sexual selection affect deleterious mutations differently, and to what extent, remains an important issue to resolve

Novel mutations in the VKORC1 gene of wild rats and mice – a response to 50 years of selection pressure by warfarin?

<p>Abstract</p> <p>Background</p> <p>Coumarin derivatives have been in world-wide use for rodent pest control for more than 50 years. Due to their retarded action as inhibitors of blood coagulation by repression of the vitamin K reductase (VKOR) activity, they are the rodenticides of choice against several species. Resistance to these compounds has been reported for rodent populations from many countries around the world and poses a considerable problem for efficacy of pest control.</p> <p>Results</p> <p>In the present study, we have sequenced the <it>VKORC1 </it>genes of more than 250 rats and mice trapped in anticoagulant-exposed areas from four continents, and identified 18 novel and five published missense mutations, as well as eight neutral sequence variants, in a total of 178 animals. Mutagenesis in <it>VKORC1 </it>cDNA constructs and their recombinant expression revealed that these mutations reduced VKOR activities as compared to the wild-type protein. However, the <it>in vitro </it>enzyme assay used was not suited to convincingly demonstrate the warfarin resistance of all mutant proteins</p> <p>Conclusion</p> <p>Our results corroborate the <it>VKORC1 </it>gene as the main target for spontaneous mutations conferring warfarin resistance. The mechanism(s) of how mutations in the <it>VKORC1 </it>gene mediate insensitivity to coumarins <it>in vivo </it>has still to be elucidated.</p