► Estimates the rate of licence surrender by older male and female drivers. ► Estimates licence holding and car driver fatalities by age to 2030. ► Car driver fatality rate is reducing fastest for ...the oldest drivers. ► Car drivers have the lowest injury accident rate per driver at age 70–79. ► Fragility causes most of the increase in fatality rate with age.
Driving licence holding in Britain is increasing for older people, particularly older women. Licence holding by men aged 40–69 has saturated at about 90%, and for women aged 30–59 at about 78%. Drivers begin to surrender licences after age 70. By age 90, 38% of women and 25% of men who held a licence at age 70 have surrendered their licences.
The paper shows the numbers of car drivers of different ages killed and injured in accidents since 1975 and the fatality and casualty rates per driver and per mile driven. The safety of older drivers is improving faster than that of younger age groups. The number of car driver fatalities aged 70 and over was highest between 1990 and 2004, and has subsequently reduced by almost 40%. For drivers aged 80 and over, the peak was in 2004 and the number has subsequently reduced by almost 50%.
The paper uses demographic projections, forecast licence holding and the trends in fatality rates to project the numbers of fatalities for drivers of different ages in Britain. This shows that fatalities among older drivers aged are likely to continue to reduce.
Fatality rates for older road users are increased by the fragility of older persons. This disguises the fact that the accident involvement rate for older drivers does not increase with age until after age 75 or 80.
Small RNA RNA-seq for microRNAs (miRNAs) is a rapidly developing field where opportunities still exist to create better bioinformatics tools to process these large datasets and generate new, useful ...analyses. We built miRge to be a fast, smart small RNA-seq solution to process samples in a highly multiplexed fashion. miRge employs a Bayesian alignment approach, whereby reads are sequentially aligned against customized mature miRNA, hairpin miRNA, noncoding RNA and mRNA sequence libraries. miRNAs are summarized at the level of raw reads in addition to reads per million (RPM). Reads for all other RNA species (tRNA, rRNA, snoRNA, mRNA) are provided, which is useful for identifying potential contaminants and optimizing small RNA purification strategies. miRge was designed to optimally identify miRNA isomiRs and employs an entropy based statistical measurement to identify differential production of isomiRs. This allowed us to identify decreasing entropy in isomiRs as stem cells mature into retinal pigment epithelial cells. Conversely, we show that pancreatic tumor miRNAs have similar entropy to matched normal pancreatic tissues. In a head-to-head comparison with other miRNA analysis tools (miRExpress 2.0, sRNAbench, omiRAs, miRDeep2, Chimira, UEA small RNA Workbench), miRge was faster (4 to 32-fold) and was among the top-two methods in maximally aligning miRNAs reads per sample. Moreover, miRge has no inherent limits to its multiplexing. miRge was capable of simultaneously analyzing 100 small RNA-Seq samples in 52 minutes, providing an integrated analysis of miRNA expression across all samples. As miRge was designed for analysis of single as well as multiple samples, miRge is an ideal tool for high and low-throughput users. miRge is freely available at http://atlas.pathology.jhu.edu/baras/miRge.html.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent genomic studies have provided a refined genetic map of acute lymphoblastic leukemia (ALL) and increased the number of potential prognostic markers. Therefore, we integrated copy-number ...alteration data from the 8 most commonly deleted genes, subordinately, with established chromosomal abnormalities to derive a 2-tier genetic classification. The classification was developed using 809 ALL97/99 patients and validated using 742 United Kingdom (UK)ALL2003 patients. Good-risk (GR) genetic features included ETV6-RUNX1, high hyperdiploidy, normal copy-number status for all 8 genes, isolated deletions affecting ETV6/PAX5/BTG1, and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. All other genetic features were classified as poor risk (PR). Three-quarters of UKALL2003 patients had a GR genetic profile and a significantly improved event-free survival (EFS) (94%) compared with patients with a PR genetic profile (79%). This difference was driven by a lower relapse rate (4% vs 17%), was seen across all patient subgroups, and was independent of other risk factors. Even genetic GR patients with minimal residual disease (>0.01%) at day 29 had an EFS in excess of 90%. In conclusion, the integration of genomic and cytogenetic data defines 2 subgroups with distinct responses to treatment and identifies a large subset of children suitable for treatment deintensification.
•Integrating cytogenetic and genomic data in pediatric ALL reveals 2 subgroups with different outcomes independent of other risk factors.•A total of 75% of children on UKALL2003 had a good-risk genetic profile, which predicted an EFS and OS of 94% and 97% at 5 years.
In 1930, the Bermondsey Public Health Department made the rather unusual decision to establish the first municipal foot clinic in Britain. This pioneering and popular clinic was founded at a time ...when the aims of public health were being renegotiated. Historical discussion of the reconceptualisation of public health in the interwar period typically depicts a paradigm shift in which public health was no longer focused solely on sanitising the physical environment, but was characterised by an additional, separate aim: the development of hygienic behaviour within patients. While this narrative has proved helpful in explaining the emergence of health education between the wars, Bermondsey's foot clinic challenges it somewhat. In essence, the foot clinic was an inventive and multifaceted attempt to treat Bermondsey's rampant poverty. Chiefly, the clinic sought to improve the occupational fitness of the population in an area where most jobs required workers to be stood up all day. In addition, the foot clinic was expected to provoke physiological and spiritual renewal by freeing patients to move more naturally, according to specific contemporary modernist theories of movement. Finally, the architecture of the building which housed the foot clinic was designed to encourage its patients to adopt more hygienic ways of living in their own homes. Thus, the clinic's aims are difficult to compartmentalise into either sanitisation of the lived environment or health education, since it sought to achieve both goals simultaneously. Fundamentally, this integrated approach to public health was rooted in a concept of health that upheld the interconnectedness of individual, communal and environmental well-being.
Toward the human cellular microRNAome McCall, Matthew N; Kim, Min-Sik; Adil, Mohammed ...
Genome research,
10/2017, Letnik:
27, Številka:
10
Journal Article
Recenzirano
Odprti dostop
MicroRNAs are short RNAs that serve as regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell-autonomously, ...and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data have caused considerable confusion, and comprehensive cell-level data do not yet exist. Here, we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent superenhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 495 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder, suggesting DROSHA- and DICER1-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to de-convolute variable cellular composition of colon and adipose tissue samples, highlighting one use of these cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.
The sophorolipid class of biosurfactants is finding increasing use in personal care as well as pharmaceutical products and has the potential to disrupt biofilm formation and inhibit the growth of a ...variety of clinically relevant organisms. In order to investigate potential biomedical applications of sophorolipids derived from nonpathogenic organisms, we fractionated and purified glycolipid biosurfactant sophorolipids produced by the yeast
, which yielded nonacetylated acidic C
congeners that were essentially free from other contaminants (>95% purity). These acidic sophorolipids have antimicrobial activities against the nosocomial infective agents
and
, with significant reductions in CFU at concentrations of as low as 5 mg ml
In addition, the sophorolipid showed similar effects against the same two bacterial strains when combined with kanamycin or cefotaxime. As a potential use of these sophorolipids is as a component of topically applied creams for the treatment of wound infections, it is clear that they must have no demonstrable adverse effect on wound healing. To assess this, we evaluated mammalian cell toxicity
using viability tests, which revealed no adverse effect on either endothelial or keratinocyte-derived cell lines with sophorolipid concentrations of < 0.5 mg ml
In addition,
experiments using a mouse skin wounding assay revealed that the time course of healing wounds was unaffected by the application of sophorolipid-containing creams, and histological examination of regenerated skin tissue confirmed that the healing process was similar to that observed for control animals, with no evidence of inflammation. These results are consistent with the suggestion that acidic sophorolipids can be used as a component of antimicrobial creams to reduce the risk of wound infection during healing.
A draft map of the human proteome Kim, Min-Sik; Pinto, Sneha M; Getnet, Derese ...
Nature,
05/2014, Letnik:
509, Številka:
7502
Journal Article
Recenzirano
Odprti dostop
The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides ...does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
What motivates individuals to regulate their emotions? One answer, which has been highlighted in emotion-regulation research, is that individuals are motivated by short-term hedonic goals (e.g. , the ...motivation to feel pleasure). Another answer, however, is that individuals are motivated by instrumental goals (e.g., the motivation to perform certain behaviors). We suggest that both answers have merit. To demonstrate the role instrumental goals may play in emotion regulation, we pitted short-term hedonic motives and instrumental motives against each other, by testing whether individuals were motivated to experience a potentially useful, albeit unpleasant, emotion. We found that (a) individuals preferred activities that would increase their level of anger (but not their level of excitement) when they were anticipating confrontational, but not nonconfrontational, tasks and that (b) anger improved performance in a confrontational, but not a nonconfrontational, task. These findings support a functional view of emotion regulation, and demonstrate that in certain contexts, individuals may choose to experience emotions that are instrumental, despite short-term hedonic costs.
With the growth of ultrasound-guided regional anesthesia, so has the requirement for training tools to practice needle guidance skills and evaluate echogenic needles. Ethically, skills in ...ultrasound-guided needle placement should be gained in a phantom before performance of nerve blocks on patients in clinical practice. However, phantom technology is varied, and critical evaluation of the images is needed to understand their application to clinical use. Needle visibility depends on the echogenicity of the needle relative to the echogenicity of the tissue adjacent the needle. We demonstrate this point using images of echogenic and nonechogenic needles in 5 different phantoms at both shallow angles (20 degrees) and steep angles (45 degrees). The echogenicity of phantoms varies enormously, and this impacts on how needles are visualized. Water is anechoic, making all needles highly visible, but does not fix the needle to allow practice placement. Gelatin phantoms and Blue Phantoms provide tactile feedback but have very low background echogenicity, which greatly exaggerates needle visibility. This makes skill acquisition easier but can lead to false confidence in regard to clinical ability. Fresh-frozen cadavers retain much of the textural feel of live human tissue and are nearly as echogenic. Similar to clinical practice, this makes needles inserted at steep angles practically invisible, unless they are highly echogenic. This review describes the uses and pitfalls of phantoms that have been described or commercially produced.
Abstract
The gecko adhesive system has inspired hundreds of synthetic mimics principally focused on replicating the strong, reversible, and versatile properties of the natural system. For geckos ...native to the tropics, versatility includes the need to remain attached to substrates that become wet from high humidity and frequent rain. Paradoxically, van der Waals forces, the principal mechanism responsible for gecko adhesion, reduce to zero when two contacting surfaces separate even slightly by entrapped water layers. A series of laboratory studies show that instead of slipping, geckos maintain and even improve their adhesive performance in many wet conditions (i.e., on wet hydrophobic substrates, on humid substrates held at low temperatures). The mechanism for this is not fully clarified, and likely ranges in scale from the chemical and material properties of the gecko’s contact structures called setae (e.g., setae soften and change surface confirmation when exposed to water), to their locomotor biomechanics and decision-making behavior when encountering water on a substrate in their natural environment (e.g., some geckos tend to run faster and stop more frequently on misted substrates than dry). Current work has also focused on applying results from the natural system to gecko-inspired synthetic adhesives, improving their performance in wet conditions. Gecko-inspired synthetic adhesives have also provided a unique opportunity to test hypotheses about the natural system in semi-natural conditions replicated in the laboratory. Despite many detailed studies focused on the role of water and humidity on gecko and gecko-inspired synthetic adhesion, there remains several outstanding questions: (1) what, if any, role does capillary or capillary-like adhesion play on overall adhesive performance of geckos and gecko-inspired synthetics, (2) how do chemical and material changes at the surface and in the bulk of gecko setae and synthetic fibrils change when exposed to water, and what does this mean for adhesive performance, and (3) how much water do geckos encounter in their native environment, and what is their corresponding behavioral response? This review will detail what we know about gecko adhesion in wet environments, and outline the necessary next steps in biological and synthetic system investigations.
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