Enhancing the Soft Tissue-Implant Seal and Reducing Bacterial Colonisation around the Intraosseous Transcutaneous Amputation Prosthesis

The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft tissue complications associated with socket prostheses and by improving sensory feedback and function. ITAP relies on a soft tissue seal forming at the skin-implant interface in order to prevent epithelial downgrowth and infection. A successful soft tissue seal is dependent on soft tissue cells winning the ‘race for the surface’ against bacteria. The current ITAP design includes a flange with drilled holes to promote soft tissue attachment. Despite this, infection remains a significant risk. This thesis aimed to investigate the effect of a fully porous titanium alloy (PT) flange with interconnected pores and fibronectin (Fn)-functionalised hydroxyapatite (HA) coatings on soft tissue integration. Silver (Ag) was incorporated into coatings for its antimicrobial properties. In vitro fibroblast viability and bacterial colonisation on HAAgFn coatings was studied. HAAgFn was applied to PT flanges of transcutaneous pins implanted into sheep tibiae. A histological assessment of soft tissue integration was undertaken and bacterial colonisation within the soft tissues and on the flange was quantified. The key original contributions to knowledge from this thesis are that firstly, HAAgFn coatings have antibacterial activity and are cytocompatible after serum- preconditioning in vitro. Secondly, in vivo, PT significantly reduces epithelial downgrowth, increases soft tissue integration and reduces bacterial colonisation compared with the current ITAP drilled-hole flange. Overall, the addition of coatings did not enhance these effects in vivo. HA reduced the favourable effects of PT. Fn and Ag counteracted some of the negative effects of HA suggesting that using these coatings without HA could improve results. In conclusion, a PT flange has the potential to reduce the susceptibility of ITAP to infection compared with the current ITAP design. It is hoped that this finding will be translated into clinical practice

Calculated line lists for H216O and H218O with extensive comparisons to theoretical and experimental sources including the HITRAN2016 database

New line lists are presented for the two most abundant water isotopologues; H216O and H218O. The H216O line list extends to 25710 cm with intensity stabilities provided via ratios of calculated intensities obtained from two different semi-empirical potential energy surfaces. The line list for H218O extends to 20000 cm. The minimum intensity considered for all is cm molecule at 296 K, assuming 100% abundance for each isotopologue. Fluctuation of calculated intensities caused by changes in the underlying potential energy are found to be significant, particularly for weak transitions. Direct comparisons are made against eighteen different sources of line intensities, both experimental and theoretical, many of which are used within the HITRAN2016 database. With some exceptions, there is excellent agreement between our line lists and the experimental intensities in HITRAN2016. In the infrared region, many H216O bands which exhibit intensity differences of 5–10% between to the most recent ’POKAZATEL’ line list (Polyansky et al., [Mon. Not. Roy. Astron. Soc. 480, 2597 (2018)] and observation, are now generally predicted to within 1%. For H218O, there are systematic differences in the strongest intensities calculated in this work versus those obtained from semi-empirical calculations. In the visible, computed cross sections show smaller residuals between our work and both HITRAN2016 and HITEMP2010 than POKAZATEL. While our line list accurately reproduces HITEMP2010 cross sections in the observed region, residuals produced from this comparison do however highlight the need to update line positions in the visible spectrum of HITEMP2010. These line lists will be used to update many transition intensities and line positions in the HITRAN2016 database

An experimentally-accurate and complete room-temperature infrared HCN line-list for the HITRAN database

A hydrogen cyanide line list (MOMeNT-90) developed for the HITRAN spectroscopic database covering 0–7500 cm−1 range (λ>1330 nm) is presented. The line list is a combination of the variationally calculated line intensities with line centers obtained from experimentally derived energy levels. There are four features of this line list which distinguishes it from the previously calculated ones. First, the intensities are variationally calculated using a new, high-accuracy potential energy surface (PES) obtained via fitting the PES using experimental energy levels. Second, a new ab initio dipole moment surface was calculated at a high level of quantum chemical theory. Based on the wave functions calculated with the new PES and use of the new dipole moment surface, line intensities are reported which of similar accuracy to those obtained experimentally. Third, the calculated states are mapped to the existing complete set of experimental eigenenergies, resulting in an assigned and complete HCN line list down to the HITRAN intensity threshold of 10−34 cm/molecule. Fourth, extensive validation of the line list is provided through line-by-line comparisons of the results with measured HCN spectra which confirms the accuracy of the intensities used to construct the line list. The line list is augmented with parameters needed to calculate line widths for pressure-dependent simulations

Hearing the voices of older adult patients: processes and findings to inform health services research

Background Clinical academic research and service improvement is planned using Patient and Public Involvement and Engagement (PPIE) but older PPIE participants are consulted less often due to the perception that they are vulnerable or hard to engage. Objectives To consult frail older adults about a recently adopted service, discharge to assess (D2A), and to prioritise services improvements and research topics associated with the design and delivery of discharge from hospital. To use successive PPIE processes to enable a permanent PPIE panel to be established. Participants Following guidance from an established hospital PPI panel 27 older adult participants were recruited. Participants from Black, Asian and Minority Ethnic (BAME) communities, affluent and non-affluent areas and varied social circumstances were included. Methods Focus groups and individual interviews were conducted in participants own homes or nearby social venues. Results Priorities for discharge included remaining independent despite often feeling lonely at home; to remain in hospital if needed; and for services to ensure effective communication with families. The main research priority identified was facilitating independence, whilst establishing a permanent PPIE panel involving older adults was viewed favourably. Conclusions Taking a structured approach to PPIE enabled varied older peoples’ voices to express their priorities and concerns into early discharge from hospital, as well as enabling the development of health services research into hospital discharge planning and management. Older people as participants identified research priorities after reflecting on their experiences. Listening and reflection enabled researchers to develop a new “Community PPIE Elders Panel” to create an enduring PPIE infrastructure for frail older housebound people to engage in research design, development and dissemination

The grinch who stole wisdom

Dr. Seuss is wise. How the Grinch Stole Christmas (Seuss, 1957) could serve as a parable for our time. It can also be seen as a roadmap for the development of contemplative wisdom. The abiding popularity of How the Grinch Stole Christmas additionally suggests that contemplative wisdom is more readily available to ordinary people, even children, than is normally thought. This matters because from the point of view of contemplatives in any of the world's philosophies or religions, people are confused about wisdom. The content of the nascent field of wisdom studies, they might say, is largely not wisdom at all but rather what it's like to live in a particular kind of prison cell, a well appointed cell perhaps, but not a place that makes possible either personal satisfaction or deep problem solving. I believe that what the contemplative traditions have to say is important; they offer a different orientation to what personal wisdom is, how to develop it, and how to use it in the world than is presently contained in either our popular culture or our sciences. In order to illustrate this I will examine, in some detail, one contemplative path within Buddhism. Buddhism is particularly useful in this respect because its practices are nontheistic and thus avoid many of the cultural landmines associated with the contemplative aspects of Western religions

Naturally-Acquired Influenza-Specific CD4+ T-Cell Proliferative Responses Are Impaired in HIV-Infected African Adults

BACKGROUND Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+) T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART. METHODS Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+) T-cell immunity. RESULTS We found lower naturally-acquired proliferative influenza-specific CD4(+) T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4(+) T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+) T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+) T-cells in peripheral blood. CONCLUSION Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations

"Flogging dead horses": evaluating when have clinical trials achieved sufficiency and stability? A case study in cardiac rehabilitation

<p>Abstract</p> <p>Background</p> <p>Most systematic reviews conclude that another clinical trial is needed. Measures of sufficiency and stability may indicate whether this is true.</p> <p>Objectives: To show how evidence accumulated on centre-based versus home-based cardiac rehabilitation, including estimates of sufficiency and stability</p> <p>Methods</p> <p>Systematic reviews of clinical trials of home versus centre-based cardiac rehabilitation were used to develop a cumulative meta-analysis over time. We calculated the standardised mean difference (SMD) in effect, confidence intervals and indicators of sufficiency and stability. Sufficiency refers to whether the meta-analytic database adequately demonstrates that an intervention works - is statistically superior to another. It does this by assessing the number of studies with null results that would be required to make the meta-analytic effect non-statistically significant. Stability refers to whether the direction and size of the effect is stable as new studies are added to the meta-analysis.</p> <p>Results</p> <p>The standardised mean effect difference reduced over fourteen comparisons from a non-significant difference favouring home-based cardiac rehabilitation to a very small difference favouring hospital (SMD -0.10, 95% CI -0.32 to 0.13). This difference did not reach the sufficiency threshold (failsafe ratio 0.039 < 1) but did achieve the criteria for stability (cumulative slope 0.003 < 0.005).</p> <p>Conclusions</p> <p>The evidence points to a relatively small effect difference which was stable but not sufficient in terms of the suggested thresholds. Sufficiency should arguably be based on substantive significance and decided by patients. Research on patient preferences should be the priority. Sufficiency and stability measures are useful tools that need to be tested in further case studies.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration