The Logic of Fashion Cycles

Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads. Here we show that realistic fashion-like dynamics emerge spontaneously if individuals can copy others' preferences for cultural traits as well as traits themselves. We demonstrate this dynamics in simple mathematical models of the diffusion, and subsequent abandonment, of a single cultural trait which individuals may or may not prefer. We then simulate the coevolution between many cultural traits and the associated preferences, reproducing power-law frequency distributions of cultural traits (most traits are adopted by few individuals for a short time, and very few by many for a long time), as well as correlations between the rate of increase and the rate of decrease of traits (traits that increase rapidly in popularity are also abandoned quickly and vice versa). We also establish that alternative theories, that fashions result from individuals signaling their social status, or from individuals randomly copying each other, do not satisfactorily reproduce these empirical observations

Designing a physical activity parenting course : parental views on recruitment, content and delivery

Background Many children do not engage in sufficient levels of physical activity (PA) and spend too much time screen-viewing (SV). High levels of SV (e.g. watching TV, playing video games and surfing the internet) and low levels of PA have been associated with adverse health outcomes. Parenting courses may hold promise as an intervention medium to change children’s PA and SV. The current study was formative work conducted to design a new parenting programme to increase children’s PA and reduce their SV. Specifically, we focussed on interest in a course, desired content and delivery style, barriers and facilitators to participation and opinions on control group provision. Methods In-depth telephone interviews were conducted with thirty two parents (29 female) of 6–8 year olds. Data were analysed thematically. An anonymous online survey was also completed by 750 parents of 6–8 year old children and descriptive statistics calculated. Results Interview participants were interested in a parenting course because they wanted general parenting advice and ideas to help their children be physically active. Parents indicated that they would benefit from knowing how to quantify their child’s PA and SV levels. Parents wanted practical ideas of alternatives to SV. Most parents would be unable to attend unless childcare was provided. Schools were perceived to be a trusted source of information about parenting courses and the optimal recruitment location. In terms of delivery style, the majority of parents stated they would prefer a group-based approach that provided opportunities for peer learning and support with professional input. Survey participants reported the timing of classes and the provision of childcare were essential factors that would affect participation. In terms of designing an intervention, the most preferred control group option was the opportunity to attend the same course at a later date. Conclusions Parents are interested in PA/SV parenting courses but the provision of child care is essential for attendance. Recruitment is likely to be facilitated via trusted sources. Parents want practical advice on how to overcome barriers and suggest advice is provided in a mutually supportive group experience with expert input

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal-contractile coupling

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Side effects and the need for secrecy: characterising discontinuation of modern contraception and its causes in Ethiopia using mixed methods

Background: Contraceptive discontinuation is a major barrier to reducing global unmet needs for family planning, but the reasons why women discontinue contraception are poorly understood. Here we use data from Ethiopia to investigate (i) the magnitude of contraceptive discontinuation in 2005-2011, (ii) how the risk of discontinuation varies with method type and education level and (iii) the barriers to continuation. Our main hypothesis is that contraceptive discontinuation is driven by the experience of physiological side-effects associated with the use of hormonal contraception, rather than a lack of formal education. Methods: We used a mixed methods explanatory sequential design to explain the quantitative results in more details through the qualitative data. First, we analysed quantitative data from the 2011 Ethiopian Demographic and Health Survey to study patterns of contraceptive discontinuation and method choice using multilevel multiprocess models. Second, we conducted semi-structured interviews and focus group discussions in the 3 most populated regions of Ethiopia with individuals of reproductive age and health professionals. Results: The analysis of EDHS data shows that the rate of discontinuation has not reduced in the period 2005-2011 and remains high. Discontinuation mainly takes the form of abandonment, and is a function of method type, age and wealth but not of educational level. Interviews with women and health professionals reveal that the experience of debilitating physiological side effects, the need for secrecy and poverty are important barriers to continuation. Conclusions: Our findings together suggest that physiological and social side-effects of contraceptive use, not a lack of formal education, are the root causes of contraceptive abandonment in Ethiopia. </p

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the 'Beijing' sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive

Evaluation of a communication skills program for first-year medical students at the University of Toronto

Abstract Background Effective doctor-patient communication has been linked to numerous benefits for both patient and physician. The purpose of this study was to evaluate the effectiveness of the University of Toronto's Therapeutic Communication Program (TCom) at improving first-year medical students' communication skills. Methods Data were collected during the 1996/97, 1997/98, 1998/99 and 1999/00 academic years. The study used a repeated measures design with a waiting list control group: students were randomly assigned to groups starting the educational intervention in either September (N = 38) or February (N = 41), with the latter being used as a control for the former. Communication skills were assessed at the pre- and post-intervention times and at the end of the academic year from the perspectives of student, standardized patient and external rater. Results Only the external rater, using an instrument designed to assess the students' empathy based on their written responses, showed a time × group interaction effect (p = 0.039), thereby partially supporting the hypothesis that TCom improved the students' communication skills. Students rated themselves less positively after participation in the program (p = 0.038), suggesting that self-evaluation was an ineffective measure of actual performance or that the program helped them learn to more accurately assess their abilities. Conclusion The lack of strong findings may be partly due to the study's small sample sizes. Further research at other medical or professional schools could assess the effectiveness of similar courses on students' communication skills and on other capacities that were not measured in this study, such as their understanding of and comfort with patients, their management of the doctor-patient relationship, and their ability to give and receive feedback

Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni, Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy

<p>Abstract</p> <p>Background</p> <p>Miltefosine, which is the first oral drug licensed for the treatment of leishmaniasis, was recently reported to be a promising lead compound for the synthesis of novel antischistosomal derivatives with potent activity <it>in vivo </it>against different developmental stages of <it>Schistosoma mansoni</it>. In this paper an <it>in vitro </it>study was carried out to investigate whether it has a biocidal activity against the aquatic stages of <it>Schistosoma mansoni </it>and its snail intermediate host, <it>Biomphalaria alexandrina </it>, thus being also a molluscicide. Additionally, to see whether miltefosine can have a broad spectrum antischistosomal activity, a similar <it>in vitro </it>study was carried out on the adult stage of <it>Schistosoma haematobium</it>, the second major human species, its larval stages and snail intermediate host, <it>Bulinus truncutes</it>. This was checked by scanning electron microscopy.</p> <p>Results</p> <p>Miltefosine proved to have <it>in vitro </it>ovicidal, schistolarvicidal and lethal activity on adult worms of both <it>Schistosoma </it>species and has considerable molluscicidal activity on their snail hosts. Scanning electron microscopy revealed several morphological changes on the different stages of the parasite and on the soft body of the snail, which further strengthens the current evidence of miltefosine's activity. This is the first report of mollusicidal activity of miltefosine and its <it>in vitro </it>schistosomicidal activity against <it>S.haematobium</it>.</p> <p>Conclusions</p> <p>This study highlights miltefosine not only as a potential promising lead compound for the synthesis of novel broad spectrum schistosomicidal derivatives, but also for molluscicidals.</p

Effects of a recombinant gene expression on ColE1-like plasmid segregation in Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Segregation of expression plasmids leads to loss of recombinant DNA from transformed bacterial cells due to the irregular distribution of plasmids between the daughter cells during cell division. Under non-selective conditions this segregational instability results in a heterogeneous population of cells, where the non-productive plasmid-free cells overgrow the plasmid-bearing cells thus decreasing the yield of recombinant protein. Amongst the factors affecting segregational plasmid instability are: the plasmid design, plasmid copy-number, host cell genotype, fermentation conditions etc. This study aims to investigate the influence of transcription and translation on the segregation of recombinant plasmids designed for constitutive gene expression in <it>Escherichia coli </it>LE392 at glucose-limited continuous cultivation. To this end a series of pBR322-based plasmids carrying a synthetic human interferon-gamma (hIFNγ) gene placed under the control of different regulatory elements (promoter and ribosome-binding sites) were used as a model.</p> <p>Results</p> <p>Bacterial growth and product formation kinetics of transformed <it>E. coli </it>LE392 cells cultivated continuously were described by a structured kinetic model proposed by Lee et al. (1985). The obtained results demonstrated that both transcription and translation efficiency strongly affected plasmid segregation. The segregation of plasmid having a deleted promoter did not exceed 5% after 190 h of cultivation. The observed high plasmid stability was not related with an increase in the plasmid copy-number. A reverse correlation between the yield of recombinant protein (as modulated by using different ribosome binding sites) and segregational plasmid stability (determined by the above model) was also observed.</p> <p>Conclusions</p> <p>Switching-off transcription of the hIFNγ gene has a stabilising effect on ColE1-like plasmids against segregation, which is not associated with an increase in the plasmid copy-number. The increased constitutive gene expression has a negative effect on segregational plasmid stability. A kinetic model proposed by Lee et al. (1985) was appropriate for description of <it>E. coli </it>cell growth and recombinant product formation in chemostat cultivations.</p