Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide

Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions

Testing equality of variances in the analysis of repeated measurements

The problem of comparing the precisions of two instruments using repeated measurements can be cast as an extension of the Pitman-Morgan problem of testing equality of variances of a bivariate normal distribution. Hawkins (1981) decomposes the hypothesis of equal variances in this model into two subhypotheses for which simple tests exist. For the overall hypothesis he proposes to combine the tests of the subhypotheses using Fisher's method and empirically compares the component tests and their combination with the likelihood ratio test. In this paper an attempt is made to resolve some discrepancies and puzzling conclusions in Hawkins's study and to propose simple modifications.\ud \ud The new tests are compared to the tests discussed by Hawkins and to each other both in terms of the finite sample power (estimated by Monte Carlo simulation) and theoretically in terms of asymptotic relative efficiencies

Genetic variation of rougheye rockfish (Sebastes aleutianus) and shortraker rockfish (S. borealis) inferred from allozymes

Rougheye rockfish (Sebastes aleutianus) and shortraker rockfish (Sebastes borealis) were collected from the Washington coast, the Gulf of Alaska, the southern Bering Sea, and the eastern Kamchatka coast of Russia (areas encompassing most of their geographic distribution) for population genetic analyses. Using starch gel electrophoresis, we analyzed 1027 rougheye rockfish and 615 shortraker rockfish for variation at 29 proteincoding loci. No genetic heterogeneity was found among shortraker rockfish throughout the sampled regions, although shortraker in the Aleutian Islands region, captured at deeper depths, were found to be significantly smaller in size than the shortraker caught in shallower waters from Southeast Alaska. Genetic analysis of the rougheye rockfish revealed two evolutionary lineages that exist in sympatry with little or no gene f low between them. When analyzed as two distinct species, neither lineage exhibited heterogeneity among regions. Sebastes aleutianus seems to inhabit waters throughout the Gulf of Alaska and more southern waters, whereas S. sp. cf. aleutianus inhabits waters throughout the Gulf of Alaska, Aleutian Islands, and Asia. The distribution of the two rougheye rockfish lineages may be related to depth where they are sympatric. The paler color morph, S. aleutianus, is found more abundantly in shallower waters and the darker color morph, Sebastes sp. cf. aleutianus, inhabits deeper waters. Sebastes sp. cf. aleutianus, also exhibited a significantly higher prevalence of two parasites, N. robusta and T. trituba, than did Sebastes aleutianus, in the 2001 samples, indicating a possible difference in habitat and (or) resource use between the two lineages

Four dimensional Lie symmetry algebras and fourth order ordinary differential equations

Realizations of four dimensional Lie algebras as vector fields in the plane are explicitly constructed. Fourth order ordinary differential equations which admit such Lie symmetry algebras are derived. The route to their integration is described.Comment: 12 page

Recruiting and retaining children and families' social workers. The potential of work discussion groups

Current difficulties with the recruitment and retention of children and families' social workers have been formally acknowledged. However, although initiatives which focus on remuneration and career progression are clearly welcome, research and evidence from practice highlights how social workers themselves place high value on the availability of good quality supervision. Yet, questions remain about whether first-line managers have the time or are even in the best position to offer this support. This article draws on the experience and evaluation of one particular model of supervision — 'work discussion groups' —and explores its impact with residential social work staff and teachers as well as the potential for further developments of this kind

Development of food photographs for use with children aged 18 months to 16 years:comparison against weighed food diaries – The Young Person’s Food Atlas (UK)

Traditional dietary assessment methods, used in the UK, such as weighed food diaries impose a large participant burden, often resulting in difficulty recruiting representative samples and underreporting of energy intakes. One approach to reducing the burden placed on the participant is to use portion size assessment tools to obtain an estimate of the amount of food consumed, removing the need to weigh all foods. An age range specific food atlas was developed for use in assessing children’s dietary intakes. The foods selected and portion sizes depicted were derived from intakes recorded during the UK National Diet and Nutrition Surveys of children aged 1.5 to 16 years. Estimates of food portion sizes using the food atlas were compared against 4-day weighed intakes along with in-school / nursery observations, by the research team. Interviews were conducted with parents the day after completion of the diary, and for children aged 4 to 16 years, also with the child. Mean estimates of portion size consumed were within 7% of the weight of food recorded in the weighed food diary. The limits of agreement were wide indicating high variability of estimates at the individual level but the precision increased with increasing age. For children 11 years and over, agreement with weighed food diaries, was as good as that of their parents in terms of total weight of food consumed and of intake of energy and key nutrients. The age appropriate food photographs offer an alternative to weighed intakes for dietary assessment with children

Microsatellite-stable diploid carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer

Chromosomal instability and microsatellite instability represent the major pathways for colorectal cancer (CRC) progression. However, a significant percentage of CRC shows neither pattern of instability, and thus represents a potentially distinctive form of the disease. Flow cytometry was used to determine the degree of DNA aneuploidy in 46 consecutive sporadic colorectal cancers. Microsatellite status was determined by PCR amplification using standard markers, while immunostaining was used to examine the expression of p53. K- ras status was determined by restriction-mediated PCR assay. Twenty-five (54%) tumours were aneuploid, 14 (30%) were diploid and microsatellite-stable and seven (15%) were diploid and microsatellite-unstable. Tumours with microsatellite instability were more likely to be right sided, to occur in women and to be associated with an improved survival. Aneuploid tumours were significantly more common in men and were likely to be left sided. The diploid microsatellite-stable (MSS) tumours did not show a sex or site predilection, but were strongly associated with the presence of metastatic disease at the time of diagnosis. Our data suggests that diploid, MSS tumours represent a biologically and phenotypically distinct subset of colorectal carcinoma, and one that is associated with the early development of metastases. We suggest that the genetic stability that characterizes these tumours may favour the maintenance of an invasive phenotype, and thus facilitate disease progression. These findings may have important implications for treatment options in this disease subset. © 2001 Cancer Research Campaign http://www.bjcancer.co

A Fast Algorithm for Robust Regression with Penalised Trimmed Squares

The presence of groups containing high leverage outliers makes linear regression a difficult problem due to the masking effect. The available high breakdown estimators based on Least Trimmed Squares often do not succeed in detecting masked high leverage outliers in finite samples. An alternative to the LTS estimator, called Penalised Trimmed Squares (PTS) estimator, was introduced by the authors in \cite{ZiouAv:05,ZiAvPi:07} and it appears to be less sensitive to the masking problem. This estimator is defined by a Quadratic Mixed Integer Programming (QMIP) problem, where in the objective function a penalty cost for each observation is included which serves as an upper bound on the residual error for any feasible regression line. Since the PTS does not require presetting the number of outliers to delete from the data set, it has better efficiency with respect to other estimators. However, due to the high computational complexity of the resulting QMIP problem, exact solutions for moderately large regression problems is infeasible. In this paper we further establish the theoretical properties of the PTS estimator, such as high breakdown and efficiency, and propose an approximate algorithm called Fast-PTS to compute the PTS estimator for large data sets efficiently. Extensive computational experiments on sets of benchmark instances with varying degrees of outlier contamination, indicate that the proposed algorithm performs well in identifying groups of high leverage outliers in reasonable computational time.Comment: 27 page

Competency Corner, Part One: Optometrists – What do we do?

In 2001 the Canadian Examiners of Optometry mandated the Competence Committee to describe the competencies required of Canadian Optometrists to provide safe and effective optometric care. The goal of this work was to provide a framework for revision of the Canadian Standard Assessment in Optometry so that questions on this exam could be directly linked to the practise-requirements of Canadian Optometrists. Work from the World Health Organization (WHO) provided an excellent foundation for the Competence Committee’s deliberations, emphasizing that Optometrists have professional responsibilities beyond providing eye and vision care. The Competence Committee followed WHO’s framework and identified four critical roles of Optometrists. These roles relate to: i. providing eye and vision care; ii. collaborating with and referring to other health care providers; iii. managing their practice, and; iv. educating within their profession. A second set of general attributes was also identified. These general attributes are needed to successfully perform the majority of the professional competencies. The Competence Committee identified five underlying general attributes: knowledge, reasoning and skills; planning and implementation; communication; values and ethics; and, selfdirected learning. The next article in this four part series provides the detailed descriptions of these professional competencies and underlying general attributes required of Canadian Optometrists

Optimum anatomic socket position and sizing for the direct anterior approach: impingement and instability

© 2019 A comprehensive strategy is important for ensuring reproducible and safe acetabular component sizing and positioning. Presented here is our approach for anatomic acetabular component positioning in direct anterior total hip arthroplasty. This strategy has evolved with our understanding of the ramifications of socket sizing and positioning on instability and impingement. Data collected by a single surgeon (J.A.R.) between 2009 and 2011 influenced our current paradigm. We compare the sizing and positioning parameters of the anterior and posterior approach, thus demonstrating how the 2 are different. By highlighting these differences, we hope to provide a clear, defined approach to acetabular placement and sizing for direct anterior-approach total hip arthroplasty