Diversity-generating machines: genetics of bacterial sugar-coating

Bacterial pathogens and commensals are surrounded by diverse surface polysaccharides which include capsules and lipopolysaccharides. These carbohydrates play a vital role in bacterial ecology and interactions with the environment. Here, we review recent rapid advancements in this field, which have improved our understanding of the roles, structures, and genetics of bacterial polysaccharide antigens. Genetic loci encoding the biosynthesis of these antigens may have evolved as bacterial diversity-generating machines, driven by selection from a variety of forces, including host immunity, bacteriophages, and cell-cell interactions. We argue that the high adaptive potential of polysaccharide antigens should be taken into account in the design of polysaccharide-targeting medical interventions like conjugate vaccines and phage-based therapies

Representing numerosity through vibration patterns

It can be useful to display information about numerosity haptically. For instance, to display the time of day or distances when visual or auditory feedback is not possible or desirable. Here, we investigated the possibility of displaying numerosity information by means of a sequence of vibration pulses. From previous studies on numerosity perception in vision, haptics and audition it is known that numerosity judgment can be facilitated by grouping. Therefore, we investigated whether perception of the number of vibration pulses in a sequence can be facilitated by temporally grouping the pulses. We found that indeed temporal grouping can lead to considerably smaller errors and lower error rates indicating that this facilitated the task, but only when participants knew in advance whether the pulses would be temporally grouped. When grouped and ungrouped series of pulses were presented randomly interleaved, there was no difference in performance. This means that temporally grouping vibration sequences can allow the sequence to be displayed at a faster rate while it remains possible to perceive the number of vibration pulses accurately if the users is aware of the temporal grouping

Predicting the duration of reach-to-grasp movements to objects with asymmetric contact surfaces.

The duration of reach-to-grasp movements is influenced by the size of the contact surfaces, such that grasping objects with smaller contact surface areas takes longer. But what is the influence of asymmetric contact surfaces? In Experiment 1a, participants reached-to-lift wooden blocks off a table top, with the contact locations for the thumb and index finger varying in surface size. The time taken to lift the block was driven primarily by the thumb contact surface, which showed a larger effect size for the dependent variable of movement duration than the index finger's contact surface. In Experiment 1b participants reached-to-grasp (but not lift) the blocks. The same effect was found with duration being largely driven by contact surface size for the thumb. Experiment 2 tested whether this finding generalised to movements towards conical frusta grasped in a different plane mounted off the table top. Experiment 2 showed that movement duration again was dictated primarily by the size of the thumb's contact surface. The thumb contact surface was the visible surface in experiments 1 and 2 so Experiment 3 explored grasping when the index finger's contact surface was visible (participants grasped the frusta with the index finger at the top). An interaction between thumb and finger surface size was now found to determine movement duration. These findings provide the first empirical report of the impact of asymmetric contact surfaces on prehension, and may have implications for scientists who wish to model reach-to-grasp behaviours

Evaluating methods for engaging children in healthcare technology design

Examples of user involvement can be found throughout healthcare literature. This extends to the design and development of healthcare technology where the involvement of users has been found to positively impact the quality and safety of products. However, there is currently little known about which methods are the most appropriate for involving children in technology development. The research applied and developed a framework to guide the use of methods in the design and development of healthcare technology for upper limb rehabilitation in children with cerebral palsy. Utilising an assessment framework to explore the suitability of four interview methods for involving children in the design and development of healthcare technology, research was carried out in primary schools in the United Kingdom. The research team i) used the assessment framework to guide the collection of information for comparing methods for involving children; ii) considered additional criteria for inclusion in the framework; and iii) gathered observations and data to comment on the criteria in relation to the four interview methods. Children were able to participate in all four interview methods, although further consideration is needed to identify how children with disabilities can be involved in design activities forming part of interview methods. Differences were found between the methods relating to their robustness, reliability, validity, efficiency, enjoyment and cost. The involvement of participants with a disability highlighted the need to develop new methods that support their inclusion in healthcare technology design work. The assessment framework applied in this research was useful to inform the comparison of methods and represents a step towards a more unified approach to understanding how best to capture the perspectives of children to develop technology that meets their needs

Effect of Endovascular Aneurysm Repair on the Volume-Outcome Relationship in Aneurysm Repair

Background— We aim to quantify the relationship between the annual caseload (volume) and outcome from elective endovascular (EVR) or open repair of abdominal aortic aneurysms (AAAs) in England between 2005 and 2007. Methods and Results— Individual patient data were obtained from the Hospital Episode Statistics. Statistical methods included multiple logistic regression models, mortality control charts, and safety plots to determine the nature of any relationship between volume and outcome. The case-mix between hospitals of different sizes was examined using observed and expected values for in-hospital mortality. Outcome measures included in-hospital mortality and hospital length of stay. Between 2005 and 2007, a total of 57 587 patients were admitted to hospitals in England with a diagnosis of AAA, and 11 574 underwent AAA repair. There were 7313 elective AAA repairs, of which 5668 (78%) were open and 1645 (22%) were EVR. In-hospital mortality rates were 5.63% for all elective AAA repairs with rates of 6.18% for open repair and 3.77% for EVR (odds ratio, 0.676; 95% CI, 0.501 to 0.913; P=0.011). High-volume aneurysm services were associated with significantly lower mortality rates overall (0.991; 0.988 to 0.994; P<0.0001), for open repairs (0.994; 0.991 to 0.998; P=0.0008), and EVR (0.989; 0.982 to 0.995; P=0.0007). Large endovascular units had low mortality rates for open repairs. Conclusion— A strong relationship existed between the volume of surgery performed and outcome from both open and endovascular aneurysm repairs. These data support the concept that abdominal aortic surgery should be performed in specialized units that meet a minimum volume threshold

Systematic Review and Meta-analysis of Long-term survival After Elective Infrarenal Abdominal Aortic Aneurysm Repair 1969-2011: 5 Year Survival Remains Poor Despite Advances in Medical Care and Treatment Strategies.

BACKGROUND: Improved critical care, pre-operative optimization, and the advent of endovascular surgery (EVAR) have improved 30 day mortality for elective abdominal aortic aneurysm (AAA) repair. It remains unknown whether this has translated into improvements in long-term survival, particularly because these factors have also encouraged the treatment of older patients with greater comorbidity. The aim of this study was to quantify how 5 year survival after elective AAA repair has changed over time. METHODS: A systematic review was performed identifying studies reporting 5 year survival after elective infrarenal AAA repair. An electronic search of the Embase and Medline databases was conducted to January 2014. Thirty-six studies, 60 study arms, and 107,814 patients were identified. Meta-analyses were conducted to determine 5 year survival and to report whether 5 year survival changed over time. RESULTS: Five-year survival was 69% (95% CI 67 to 71%, I(2) = 87%). Meta-regression on study midpoint showed no improvement in 5 year survival over the period 1969-2011 (log OR -0.001, 95% CI -0.014-0.012). Larger average aneurysm diameter was associated with poorer 5 year survival (adjusted log OR -0.058, 95% CI -0.095 to -0.021, I(2) = 85%). Older average patient age at surgery was associated with poorer 5 year survival (adjusted log OR -0.118, 95% CI -0.142 to -0.094, I(2) = 70%). After adjusting for average patient age, an improvement in 5 year survival over the period that these data spanned was obtained (adjusted log OR 0.027, 95% CI 0.012 to 0.042). CONCLUSION: Five-year survival remains poor after elective AAA repair despite advances in short-term outcomes and is associated with AAA diameter and patient age at the time of surgery. Age-adjusted survival appears to have improved; however, this cohort as a whole continues to have poor long-term survival. Research in this field should attempt to improve the life expectancy of patients with repaired AAA and to optimise patient selection

The Cambridge Sympathy Test: Self-reported sympathy and distress in autism

Abstract Background: Difficulties with aspects of social interaction, including empathy, comprise a core symptom of autism spectrum conditions (autism). Sympathy is a specific form of empathy and involves both cognitive and affective empathy. Data are presented from a new task of self-reported sympathy and personal distress. Methods: Participants with autism (93 males; 161 females) and controls (40 males, 93 females) took part in an online survey via the Autism Research Centre or Cambridge Psychology websites. Participants completed a task where they were asked to rate photographic images that were either of distressing, neutral or happy scenes, according to the amount of sympathy they had for the individual in the photo and the degree of personal distress they felt. All participants also completed the Empathy Quotient (EQ). Results: Significant differences were found between the autism and control groups for both self-reported sympathy and personal distress, with participants with autism giving lower ratings than controls. Control females scored significantly higher than control males in both sympathy and distress. Sympathy and distress ratings in the autism group did not differ significantly by sex. EQ showed positive correlations with sympathy and distress scores. Conclusions: Using a new measure of self-reported sympathy, we found that both males and females with autism gave lower ratings of sympathy when viewing people in distressing scenarios, compared to controls.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115300, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007 - 2013) and EFPIA companies' in kind contribution. The authors were also supported by Autism Research Trust, the MRC and the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust

Major histocompatibility complex (MHC) class II-positive dendritic cells in the rat iris - In situ development from MHC class II-negative precursors

Purpose. To examine the postnatal development of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) in the iris of the normal rat eye. Methods. Single-and double-color immunomorphologic studies were performed on whole mounts prepared from rat iris taken at selected postnatal ages (2 to 3 days to 78 weeks). Immunopositive cells were enumerated, using a quantitative light microscope, and MHC class II expression on individual cells was assessed by microdensitometric analysis. Results. Major histocompatibility class II-positive DCs in the iris developed in an age-dependent manner and reached adult-equivalent density and structure at approximately 10 weeks of age, considerably later than previously described in other DC populations in the rat. In contrast, the anti-rat DC monoclonal antibody OX62 revealed a population of cells present at adult-equivalent levels as early as 3 weeks after birth. Dual-color immunostaining and microdensitometric analysis demonstrated that during postnatal growth, development of the network of MHC class II-positive DCs was a consequence of the progressive increase in expression of MHC class II antigen by OX62-positive cells. Conclusions. During postnatal growth, the DC population of the iris develops initially as an OX62-positive-MHC class II-negative population, which then develops increasing MHC class II expression in situ and finally resembles classic DC populations in other tissue sites. Maturation of the iris DC population is temporally delayed compared with time to maturation in other tissue sites in the rat

An in vitro study into the accuracy of a novel method for recording the mandibular transverse horizontal axis.

OBJECTIVES: To assess the accuracy of a novel, non-invasive method for determining the axis of rotation of articulated dental study casts. METHOD: A 3D structured light scanner was constructed using a projector and two CMOS cameras. Dental stone casts were arbitrarily mounted on an average value articulator. With the teeth together, sets of 10 scans were taken from three different viewpoints. Each scan captured approximately six upper teeth and six lower teeth. The teeth were then propped open, creating 10mm of incisal separation, and the three sets of 10 scans were repeated. From each pair of scans an axis of rotation was calculated using custom software. A total of 900 axes were created this way. The locations of these axes were plotted in sagittal planes located 57.5mm left and right of the midline to represent the position of the temporo-mandibular joints (TMJs). The accuracy of axis location was then assessed. RESULTS: The average radius of error of the individual axes, compared to the real axis, was 2.65 ± 1.01 mm. 61.3% of the axes lay within 3mm of the true axis, and 99.2% of the axes lay within 5mm of the true axis. CONCLUSIONS: The accuracy of this method is clinically acceptable. Further studies are required to confirm the accuracy of the virtual inter-occlusal records at the level of the dentition. Clinical studies are then indicated to determine whether the transverse horizontal axis on a patient can similarly be determined

Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor

Age-associated changes in stem cell populations have been implicated in age-related diseases, including cancer. However, little is known about the underlying molecular mechanisms that link aging to the modulation of adult stem cell populations. Drosophila midgut is an excellent model system for the study of stem cell renewal and aging. Here we describe an age-related increase in the number and activity of intestinal stem cells (ISCs) and progenitor cells in Drosophila midgut. We determined that oxidative stress, induced by paraquat treatment or loss of catalase function, mimicked the changes associated with aging in the midgut. Furthermore, we discovered an age-related increase in the expression of PVF2, a Drosophila homologue of human PDGF/VEGF, which was associated with and required for the age-related changes in midgut ISCs and progenitor cell populations. Taken together, our findings suggest that PDGF/VEGF may play a central role in age-related changes in ISCs and progenitor cell populations, which may contribute to aging and the development of cancer stem cells