Epidemiological reference ranges for low-density lipoprotein cholesterol and apolipoprotein B for identification of increased risk of ischaemic heart disease

Although there is widespread acceptance that total cholesterol (TC) value reference ranges should be based on epidemiological rather than statistical considerations, the epidemiological action limits for Iow-density lipoprotein cholesterol (LDL-C) are still incomplete and only statistical reference ranges for apolipoprotein B (Apo-B) levels are available. The combined use of epidemiological reference ranges for TC and incomplete or statistical reference ranges for LDL-C and Apo-B is illogical, since these parameters may fall into discordant risk categories that will hamper and complicate the management of hypercholesterolaemia. Based on a study of Iipograms obtained from ± 3 000 inhabitants of two industrialised Transvaal towns, the agerelated epidemiological reference ranges for LDL-C and ApoB were established. A comparison with published observational studies of other populations, in which comparable lipid, lipoprotein and apolipoprotein methodologies were used, reflected the severity of these lipid-related abnormalities in white South Africans, especially after the age of 30 years. In addition, the serum TC values found in this survey were not significantly different from those obtained 10 years ago

A multi-dimensional investigation of self-regulated learning in a blended classroom context : a case study on eLDa MOOC

Online systems such as massive open online courses (MOOCs) are new innovative learning technology in education. With the proliferation of MOOC systems, little has been mentioned about blended MOOC system and how it enhances students’ performance. Blended classroom is a form of learning taking place between two different activities of which one is online and the other is traditional teaching method using bricks and mortal classroom settings. This study reveals the effectiveness of blended classroom teaching for an undergraduate course. The module was embedded in an eLDa MOOC platform, which is a platform for delivery computing concepts, and Python programme course. This research aims to investigate students’ perceptions of self-regulated learning (SRL) habits. A multi-dimensional survey was designed to evaluate each aspect of SRL skills, motivation and attaining better grades within the course. This research analysis explores (a) cognitive process of students improving their self-regulated learning skills (b) potential of students’ preparedness and motivation to engage with the course content in a blended context (c) potential difference in addressing the relation among the methods of engagement and achievement in their weekly assessment results. The research applied an online self-regulated learning questionnaire (OSLQ) as the instrument for measuring the self-regulated learning skills of the students in the learning platform environment. In relation to developing a revised OSLQ to address the use of the instrument to measure self-regulated learning in an online blended classroom context. Data collection process was conducted on a sample of first year undergraduate students who took a seminar module via a blended course format. The results indicate the level of self-regulated learning explored from the measure of the self-regulation in the blended learning environment in this study

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Mid-term outcomes for Endoscopic versus Open Vein Harvest: a case control study

<p>Abstract</p> <p>Background</p> <p>Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years.</p> <p>Methods</p> <p>We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed.</p> <p>Results</p> <p>Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06).</p> <p>Conclusions</p> <p>While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.</p

The test characteristics of head circumference measurements for pathology associated with head enlargement: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The test characteristics of head circumference (HC) measurement percentile criteria for the identification of previously undetected pathology associated with head enlargement in primary care are unknown.</p> <p>Methods</p> <p>Electronic patient records were reviewed to identify children age 3 days to 3 years with new diagnoses of intracranial expansive conditions (IEC) and metabolic and genetic conditions associated with macrocephaly (MGCM). We tested the following HC percentile threshold criteria: ever above the 95^th, 97^th, or 99.6^thpercentile and ever crossing 2, 4, or 6 increasing major percentile lines. The Centers for Disease Control and World Health Organization growth curves were used, as well as the primary care network (PCN) curves previously derived from this cohort.</p> <p>Results</p> <p>Among 74,428 subjects, 85 (0.11%) had a new diagnosis of IEC (n = 56) or MGCM (n = 29), and between these 2 groups, 24 received intervention. The 99.6^thpercentile of the PCN curve was the only threshold with a PPV over 1% (PPV 1.8%); the sensitivity of this threshold was only 15%. Test characteristics for the 95th percentiles were: sensitivity (CDC: 46%; WHO: 55%; PCN: 40%), positive predictive value (PPV: CDC: 0.3%; WHO: 0.3%; PCN: 0.4%), and likelihood ratios positive (LR+: CDC: 2.8; WHO: 2.2; PCN: 3.9). Test characteristics for the 97th percentiles were: sensitivity (CDC: 40%; WHO: 48%; PCN: 34%), PPV (CDC: 0.4%; WHO: 0.3%; PCN: 0.6%), and LR+ (CDC: 3.6; WHO: 2.7; PCN: 5.6). Test characteristics for crossing 2 increasing major percentile lines were: sensitivity (CDC: 60%; WHO: 40%; PCN: 31%), PPV (CDC: 0.2%; WHO: 0.1%; PCN: 0.2%), and LR+ (CDC: 1.3; WHO: 1.1; PCN: 1.5).</p> <p>Conclusions</p> <p>Commonly used HC percentile thresholds had low sensitivity and low positive predictive value for diagnosing new pathology associated with head enlargement in children in a primary care network.</p

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

INTRODUCTION: This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line). METHODS: The BRI-JM01, BRI-JM04, and BRI-JM05 cell lines were analyzed for transgene expression, their general growth characteristics, and their sensitivities to several growth factors from the epidermal growth factor (EGF) and TGF-β families (recombinant human EGF, heregulin-β(1 )and TGF-β(1)). The BRI-JM01 cells were observed to undergo a striking morphologic change in response to TGF-β(1), and they were therefore further investigated for their ability to undergo a TGF-β-induced epithelial-to-mesenchymal transition (EMT) using motility assays and immunofluorescence microscopy. RESULTS: We found that two of the three cell lines (BRI-JM04 and BRI-JM05) express the Neu transgene, whereas, unexpectedly, both of the cell lines that were established from MMTV/activated Neu + TβRII-AS bigenic tumors (BRI-JM01 and BRI-JM05) do not express the TβRII-AS transgene. The cuboidal BRI-JM01 cells exhibit a short doubling time and are able to form confluent monolayers. The BRI-JM04 and BRI-JM05 cell lines are morphologically much less uniform, grow at a much slower rate, and do not form confluent monolayers. Only the BRI-JM05 cells can form colonies in soft agar. In contrast, all three cell lines form colonies in Matrigel, although the BRI-JM04 and BRI-JM05 cell lines do so more efficiently than the BRI-JM01 cell line. All three cell lines express the cell surface marker E-cadherin, confirming their epithelial character. Proliferation assays showed that the three cell lines respond differently to recombinant human EGF and heregulin-β(1), and that all are growth inhibited by TGF-β(1), but that only the BRI-JM01 cell line undergoes an EMT and exhibits increased motility upon TGF-β(1 )treatment. CONCLUSION: We suggest that the BRI-JM04 and BRI-JM05 cell lines can be used to investigate Neu oncogene driven mammary tumorigenesis, whereas the BRI-JM01 cell line will be useful for studying TGF-β(1)-induced EMT

I Know My Neighbour: Individual Recognition in Octopus vulgaris

Background: Little is known about individual recognition (IR) in octopuses, although they have been abundantly studied for their sophisticated behaviour and learning capacities. Indeed, the ability of octopuses to recognise conspecifics is suggested by a number of clues emerging from both laboratory studies (where they appear to form and maintain dominance hierarchies) and field observations (octopuses of neighbouring dens display little agonism between each other). To fill this gap in knowledge, we investigated the behaviour of 24 size-matched pairs of Octopus vulgaris in laboratory conditions. Methodology/Principal Findings: The experimental design was composed of 3 phases: Phase 1 (acclimatization): 12 ‘‘sightallowed’’ (and 12 ‘‘isolated’’) pairs were maintained for 3 days in contiguous tanks separated by a transparent (and opaque) partition to allow (and block) the vision of the conspecific; Phase 2 (cohabitation): members of each pair (both sight-allowed and isolated) were transferred into an experimental tank and were allowed to interact for 15 min every day for 3 consecutive days; Phase 3 (test): each pair (both sight-allowed and isolated) was subject to a switch of an octopus to form pairs composed of either familiar (‘‘sham switches’’) or unfamiliar conspecifics (‘‘real switches’’). Longer latencies (i.e. the time elapsed from the first interaction) and fewer physical contacts in the familiar pairs as opposed to the unfamiliar pairs were used as proxies for recognition. Conclusions: Octopuses appear able to recognise conspecifics and to remember the individual previously met for at leas

Atypical Balance between Occipital and Fronto-Parietal Activation for Visual Shape Extraction in Dyslexia

Reading requires the extraction of letter shapes from a complex background of text, and an impairment in visual shape extraction would cause difficulty in reading. To investigate the neural mechanisms of visual shape extraction in dyslexia, we used functional magnetic resonance imaging (fMRI) to examine brain activation while adults with or without dyslexia responded to the change of an arrow’s direction in a complex, relative to a simple, visual background. In comparison to adults with typical reading ability, adults with dyslexia exhibited opposite patterns of atypical activation: decreased activation in occipital visual areas associated with visual perception, and increased activation in frontal and parietal regions associated with visual attention. These findings indicate that dyslexia involves atypical brain organization for fundamental processes of visual shape extraction even when reading is not involved. Overengagement in higher-order association cortices, required to compensate for underengagment in lower-order visual cortices, may result in competition for top-down attentional resources helpful for fluent reading.Ellison Medical FoundationMartin Richmond Memorial FundNational Institutes of Health (U.S.). (Grant UL1RR025758)National Institutes of Health (U.S.). (Grant F32EY014750-01)MIT Class of 1976 (Funds for Dyslexia Research

Synchronized Retrovirus Fusion in Cells Expressing Alternative Receptor Isoforms Releases the Viral Core into Distinct Sub-cellular Compartments

Disparate enveloped viruses initiate infection by fusing with endosomes. However, the highly diverse and dynamic nature of endosomes impairs mechanistic studies of fusion and identification of sub-cellular sites supporting the nucleocapsid release. We took advantage of the extreme stability of avian retrovirus-receptor complexes at neutral pH and of acid-dependence of virus-endosome fusion to isolate the latter step from preceding asynchronous internalization/trafficking steps. Viruses were trapped within endosomes in the presence of NH4Cl. Removal of NH4Cl resulted in a quick and uniform acidification of all subcellular compartments, thereby initiating synchronous viral fusion. Single virus imaging demonstrated that fusion was initiated within seconds after acidification and often culminated in the release of the viral core from an endosome. Comparative studies of cells expressing either the transmembrane or GPI-anchored receptor isoform revealed that the transmembrane receptor delivered the virus to more fusion-permissive compartments. Thus the identity of endosomal compartments, in addition to their acidity, appears to modulate viral fusion. A more striking manifestation of the virus delivery to distinct compartments in the presence of NH4Cl was the viral core release into the cytosol of cells expressing the transmembrane receptor and into endosomes of cells expressing the GPI-anchored isoform. In the latter cells, the newly released cores exhibited restricted mobility and were exposed to a more acidic environment than the cytoplasm. These cores appear to enter into the cytosol after an additional slow temperature-dependent step. We conclude that the NH4Cl block traps the virus within intralumenal vesicles of late endosomes in cells expressing the GPI-anchored receptor. Viruses surrounded by more than one endosomal membrane release their core into the cytoplasm in two steps – fusion with an intralumenal vesicle followed by a yet unknown temperature-dependent step that liberates the core from late endosomes