Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development

Economic burden of adverse drug reactions and potential for pharmacogenomic testing in Singaporean adults.

Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously. The economic burden of ADRs was assessed from two perspectives: (1) Total cost and (2) incremental costs. The breakeven cost of PGx testing was estimated by dividing avoidable hospitalization costs for ADRs due to selected drugs by the number of patients taking those drugs. The total cost of 81 admissions caused by ADRs was US$570,404. Costs were significantly higher for bleeding/elevated international normalized ratio (US$9906 vs. US$2251, p = 6.58 × 10-3) compared to other ADRs, and for drugs acting on the blood coagulation system (US$9884 vs. US$2229, p = 4.41 × 10-3) compared to other drug classes. There were higher incremental laboratory costs due to ADRs causing or being present at admission. The estimated breakeven cost of a pre-emptive PGx test for patients taking warfarin, clopidogrel, chemotherapeutic and neuropsychiatric drugs was US$114 per patient. These results suggest that future studies designed to directly measure the clinical and cost impact of a pre-emptive genotyping program will help inform clinical practice and health policy decisions

Haptic feedback from human tissues of various stiffness and homogeneity

This work presents methods for haptic modelling of soft and hard tissue with varying stiffness. The model provides visualization of deformation and calculates force feedback during simulated epidural needle insertion. A spring-mass-damper (SMD) network is configured from magnetic resonance image (MRI) slices of patient’s lumbar region to represent varying stiffness throughout tissue structure. Reaction force is calculated from the SMD network and a haptic device is configured to produce a needle insertion simulation. The user can feel the changing forces as the needle is inserted through tissue layers and ligaments. Methods for calculating the force feedback at various depths of needle insertion are presented. Voxelization is used to fill ligament surface meshes with spring mass damper assemblies for simulated needle insertion into soft and hard tissues. Modelled vertebrae cannot be pierced by the needle. Graphs were produced during simulated needle insertions to compare the applied force to haptic reaction force. Preliminary saline pressure measurements during Tuohy epidural needle insertion are also used as a basis for forces generated in the simulation

Devices for accurate placement of epidural Tuohy needle for Anaesthesia administration

The aim of this project is to design two sterile devices for epidural needle insertion which can measure in real time (i) the depth of needle tip during insertion and (ii) interspinous pressure changes through a pressure measurement device as the epidural needle is advanced through the tissue layers. The length measurement device uses a small wireless camera with video processing computer algorithms which can detect and measure the moving needle. The pressure measurement device uses entirely sterile components including a pressure transducer to accurately measure syringe saline in mmHg. The data from these two devices accurately describe a needle insertion allowing comparison or review of insertions. The data was then cross-referenced to pre-measured data from MRI or ultrasound scan to identify how ligament thickness correlates to our measured depth and pressure data. The developed devices have been tested on a porcine specimen during insertions performed by experienced anaesthetists. We have obtained epidural pressures for each ligament and demonstrated functionality of our devices to measure pressure and depth of epidural needle during insertion. This has not previously been possible to monitor in real-time. The benefits of these devices are (i) to provide an alternative method to identify correct needle placement during the procedure on real patients. (ii) The data describing the speed, depth and pressure during insertion can be used to configure an epidural simulator, simulating the needle insertion procedure. (iii) Our pressure and depth data can be compared to pre-measured MRI and ultrasound to identify previously unknown links between epidural pressure and depth with BMI, obesity and body shapes

A survey of trainees’ perspectives on epidural training in the United Kingdom

Background: Establishment of epidural analgesia is one of the most difficult technical skills in which to become proficient. We explored the current United Kingdom system of training in epidural insertion amongst trainee members of the Obstetric Anaesthetists’ Association (OAA). Methods: An electronic questionnaire was sent to 452 OAA trainee members in May 2012. Questions were based upon own personal experience, challenges currently faced and the use of epidural simulation to enhance training. Results: Although the majority felt ready and prepared when initially performing epidurals solo, 66% found the experience very stressful and 25% felt under considerable time pressure. Although senior support was readily available, 36% felt uncertain much of the time and 9% were unsure when to call for help. The European Working Time Directive was felt to have impacted upon training by 54% of respondents. 40% believe that there exists more challenging patients who require more experienced operators. Although 53% had used an epidural simulator previously, 84% would recommend its use for trainees and 49% would support simulator use as a compulsory element of training. Conclusions: In spite of changes to the medical profession, there appears to be a robust system of training for epidural analgesia. However, there still exists the need to reduce the impact of the learning curve upon workplace stress for trainees. Whether this involves increased direct supervision for more than just the bare minimum, structured feedback tools to enhance the supervisor/trainee experience or the use of high-fidelity epidural simulation remains to be seen

MRI based patient-specific computer models of vertebrae, ligament and soft tissue with various density for epidural needle insertion simulation

Epidural simulations previously used layers of synthetic silicate materials to represent tissues. Graphical modelling has enabled visual representation of vertebrae and tissues. The accuracy with which previous simulators modelled the physical properties of tissue layer deformation, density distributions and reaction force during needle insertion has been lacking. Anatomical models are generally static, not considering individual differences between patients especially in obese. Our developed epidural simulator aimed to solve these issues. MRI scans of patients were taken after receiving epidural. The MRI and pressure measurement data was used to reconstruct a density model of the tissues, ligament and vertebrae taking into account the internal structure revealed by MRI intensities. Models were generated from MRI matching individual patients with tissue density varying throughout layers, matching the in vivo tissue. When patient MRI is not available a neural network is alternatively used to estimate the patient's ligament thicknesses with over 92% accuracy. A haptic device is incorporated with the graphics tissue model allowing anaesthetists to practice inserting a needle into the simulated epidural space. Changes in pressure, force and resistance to insertion can be felt as the needle pierces each layer of fat and ligament. The main problem with learning to perform epidural is the inability to see the needle location beneath the skin. MRI reveals the internal tissue structure so that anaesthetists can practice insertions on patient-specific models, visualising epidural space distance and needle obstructions. The developed simulator provides a realistic platform to practice and reduces risks of problems during in-vivo procedures

Sorrow, coping and resiliency: parents of children with cerebral palsy share their experiences.

Purpose: To explore the grieving, coping and resiliency experiences of parents of children with cerebral palsy (CP) and to investigate the suitability of chronic sorrow theory as a framework to understand those experiences. Methods: This study combined focus groups with a web-based cross-sectional survey to explore chronic sorrow in parents of children with CP. Eight parents of children with CP participated in focus groups. The discussion was transcribed verbatim and thematic analysis was performed. A further 94 parents participated in the web-based survey study in which they completed the Adapted Burke Questionnaire on chronic sorrow. A content analysis of responses was used to confirm the primary qualitative analysis. Results: The reports of parents in the focus group were consistent with chronic sorrow theory, as were the responses of parents to the web-based survey. Some parents found the diagnosis itself a distressing time whereas others found it a relief. Parents reported that times of medical and allied health intervention were particularly challenging. Conclusion: Chronic sorry theory is a useful way of understanding the experiences of parents of children with CP. It is recommended that health practitioners are mindful that, even years after diagnosis, parents of children with CP may experience intensified chronic sorrow symptoms following a triggering event and that this is normal

Magnetic properties of exchange biased and of unbiased oxide/permalloy thin layers: a ferromagnetic resonance and Brillouin scattering study

Microstrip ferromagnetic resonance and Brillouin scattering are used to provide a comparative determination of the magnetic parameters of thin permalloy layers interfaced with a non-magnetic (Al2O3) or with an antiferromagnetic oxide (NiO). It is shown that the perpendicular anisotropy is monitored by an interfacial surface energy term which is practically independent of the nature of the interface. In the investigated interval of thicknesses (5-25 nm) the saturation magnetisation does not significantly differ from the reported one in bulk permalloy. In-plane uniaxial anisotropy and exchange-bias anisotropy are also derived from this study of the dynamic magnetic excitations and compared to our independent evaluations using conventional magnetometryComment: 7 pages, 6 figures, submited to Journal of Physics: Condensed Matte