Individual Characteristics Associated with Mismatches between Self-Reported and Accelerometer-Measured Physical Activity

Background: Accurate assessment tools are required for the surveillance of physical activity (PA) levels and the assessment of the effect of interventions. In addition, increasing awareness of PA is often used as the first step in pragmatic behavioural interventions, as discrepancies between the amount of activity an individual perceives they do and the amount actually undertaken may act as a barrier to change. Previous research has demonstrated differences in the amount of activity individuals report doing, compared to their level of physical activity when measured with an accelerometer. Understanding the characteristics of those whose PA level is ranked differently when measured with either self-report or accelerometry is important as it may inform the choice of instrument for future research. The aim of this project was to determine which individual characteristics are associated with differences between self-reported and accelerometer measured physical activity.

Methods: Participant data from the 2009 wave of the Commuting and Health in Cambridge study were used. Quartiles of self-reported and accelerometer measured PA were derived by ranking each measure from lowest to highest. These quartiles were compared to determine whether individuals’ physical activity was ranked higher by either method. Multinomial logistic regression models were used to investigate the individual characteristics associated with different categories of mismatch.

Results: Data from 486 participants (70% female) were included in the analysis. In adjusted analyses, the physical activity of overweight or obese individuals was significantly more likely to be ranked higher by self-report than by accelerometer than that of normal-weight individuals (OR = 2.07, 95%CI = 1.28–3.34), particularly among women (OR = 3.97, 95%CI = 2.11–7.47).

Conclusions: There was a greater likelihood of mismatch between self-reported and accelerometer measured physical activity levels in overweight or obese adults. Future studies in overweight or obese adults should consider employing both methods of measurement.

Spatial allocation of material flow analysis in residential developments: a case study of Kildare County, Ireland

Studies of urban metabolism provide important insights for environmental management of cities, but are not widely used in planning practice due to a mismatch of data scale and coverage. This paper introduces the Spatial Allocation of Material Flow Analysis (SAMFA) model as a potential decision support tool aimed as a contribution to overcome some of these difficulties and describes its pilot use at the county level in the Republic of Ireland. The results suggest that SAMFA is capable of identifying hotspots of higher material and energy use to support targeted planning initiatives, while its ability to visualise different policy scenarios supports more effective multi-stakeholder engagement. The paper evaluates this pilot use and sets out how this model can act as an analytical platform for the industrial ecology–spatial planning nexus.

Factors influencing survival after kidney transplant failure

BACKGROUND: The failure of a kidney transplant is now a common reason for initiation of dialysis therapy. Kidney transplant recipients commencing dialysis have greater morbidity and mortality than transplant-naïve, incident dialysis patients. This study aimed to identify variables associated with survival after graft failure.

METHODS: All recipients of first, deceased donor kidney transplants performed in Northern Ireland between 1986 and 2005 who had a functioning graft at 12 months were included (n = 585). Clinical and blood-derived variables (age, gender, primary renal disease, diabetic status, smoking status, human leukocyte antigen (HLA) mismatch, acute rejection episodes, immunosuppression, cardiovascular disease, graft survival, haemoglobin, albumin, phosphate, C reactive protein, estimated glomerular filtration rate (eGFR), rate of eGFR decline, dialysis modality, and access) were collected prospectively and investigated for association with re-transplantation and survival. The association between re-transplantation and survival was explored by modelling re-transplantation as a time-dependent covariate.

RESULTS: Median follow-up time was 12.1 years. Recipients with a failing graft (158/585) demonstrated rapid loss of eGFR prior to graft failure, reducing the time available to plan for alternative renal replacement therapy. Median survival after graft failure was 3.0 years. In multivariate analysis, age and re-transplantation were associated with survival after graft failure. Re-transplantation was associated with an 88% reduction in mortality.

CONCLUSIONS: Optimal management of kidney transplant recipients with failing grafts requires early recognition of declining function and proactive preparation for re-transplantation given the substantial survival benefit this confers. The survival benefit associated with re-transplantation persists after prolonged exposure to immunosuppressive therapy.

Estimated Glomerular Filtration Rate Decline as a Predictor of Dialysis in Kidney Transplant Recipients

BACKGROUND: It is now common for individuals to require dialysis following the failure of a kidney transplant. Management of complications and preparation for dialysis are suboptimal in this group. To aid planning, it is desirable to estimate the time to dialysis requirement. The rate of decline in the estimated glomerular filtration rate (eGFR) may be used to this end.

METHODS: This study compared the rate of eGFR decline prior to dialysis commencement between individuals with failing transplants and transplant-naïve patients. The rate of eGFR decline was also compared between transplant recipients with and without graft failure. eGFR was calculated using the four-variable MDRD equation with rate of decline calculated by least squares linear regression.

RESULTS: The annual rate of eGFR decline in incident dialysis patients with graft failure exceeded that of the transplant-naïve incident dialysis patients. In the transplant cohort, the mean annual rate of eGFR decline prior to graft failure was 7.3 ml/min/1.73 m(2) compared to 4.8 ml/min/1.73 m(2) in the transplant-naïve group (p < 0.001) and 0.35 ml/min/1.73 m(2) in recipients without graft failure (p < 0.001). Factors associated with eGFR decline were recipient age, decade of transplantation, HLA mismatch and histological evidence of chronic immunological injury.

CONCLUSIONS: Individuals with graft failure have a rapid decline in eGFR prior to dialysis commencement. To improve outcomes, dialysis planning and management of chronic kidney disease complications should be initiated earlier than in the transplant-naïve population.

Real-time temperature estimation for power MOSFETs considering thermal aging effects

This paper presents a novel real-time power-device temperature estimation method that monitors the power MOSFET's junction temperature shift arising from thermal aging effects and incorporates the updated electrothermal models of power modules into digital controllers. Currently, the real-time estimator is emerging as an important tool for active control of device junction temperature as well as online health monitoring for power electronic systems, but its thermal model fails to address the device's ongoing degradation. Because of a mismatch of coefficients of thermal expansion between layers of power devices, repetitive thermal cycling will cause cracks, voids, and even delamination within the device components, particularly in the solder and thermal grease layers. Consequently, the thermal resistance of power devices will increase, making it possible to use thermal resistance (and junction temperature) as key indicators for condition monitoring and control purposes. In this paper, the predicted device temperature via threshold voltage measurements is compared with the real-time estimated ones, and the difference is attributed to the aging of the device. The thermal models in digital controllers are frequently updated to correct the shift caused by thermal aging effects. Experimental results on three power MOSFETs confirm that the proposed methodologies are effective to incorporate the thermal aging effects in the power-device temperature estimator with good accuracy. The developed adaptive technologies can be applied to other power devices such as IGBTs and SiC MOSFETs, and have significant economic implications. 

A new comparator account of auditory verbal hallucinations: how motor prediction can plausibly contribute to the sense of agency for inner speech

The comparator account holds that processes of motor prediction contribute to the sense of agency by attenuating incoming sensory information and that disruptions to this process contribute to misattributions of agency in schizophrenia. Over the last 25 years this simple and powerful model has gained widespread support not only as it relates to bodily actions but also as an account of misattributions of agency for inner speech, potentially explaining the etiology of auditory verbal hallucination (AVH). In this paper we provide a detailed analysis of the traditional comparator account for inner speech, pointing out serious problems with the specification of inner speech on which it is based and highlighting inconsistencies in the interpretation of the electrophysiological evidence commonly cited in its favor. In light of these analyses we propose a new comparator account of misattributed inner speech. The new account follows leading models of motor imagery in proposing that inner speech is not attenuated by motor prediction, but rather derived directly from it. We describe how failures of motor prediction would therefore directly affect the phenomenology of inner speech and trigger a mismatch in the comparison between motor prediction and motor intention, contributing to abnormal feelings of agency. We argue that the new account fits with the emerging phenomenological evidence that AVHs are both distinct from ordinary inner speech and heterogeneous. Finally, we explore the possibility that the new comparator account may extend to explain disruptions across a range of imagistic modalities, and outline avenues for future research.

Engendering Hope: A person-centred reflection on technology and gender

This paper examines instances of recent musical and artistic works and asks to what extent it makes sense to regard certain practices and technologies as gendered. It looks at a number of strategies for making, suggesting that male gender stereotypes are as prevalent and unhelpful (to practitioners) as female ones. It looks at aspects of the working environments of practitioners to determine whether changes in such conditions might alleviate the gender mismatch in enrolment in higher education courses featuring ubiquitous technologies. The paper identifies historical precedents for technology gendering in which readings of such gendering have shifted radically, suggesting they offer scope for optimism in our longer-term reading of the gendered-ness of current practices. The paper also touches on the extent to which a ‘research’ ethos––the foregrounding of the essential human attributes of inquisitiveness and empathy––may contribute to our capacity to tell better, less binary stories of otherness in all its forms.

Population genetic analyses reveal distinct geographical blooms of the jellyfish Rhizostoma octopus (Scyhpozoa)

Understanding the spatial integrity and connectivity of jellyfish blooms is important for ecologists and coastal stakeholders alike. Previous studies have shown that the distribution of jellyfish blooms can display a marked consistency in space and time, suggesting that such patterns cannot be attributed to passive processes alone. In the present study, we used a combination of microsatellite markers and mitochondrial cytochrome oxidase I sequences to investigate genetic structuring of the scyphozoan jellyfish Rhizostoma octopus in the Irish and Celtic Seas. The mitochondrial data indicated far higher levels of population differentiation than the microsatellites: ΦST[MT] = 0.300 vs. ΦST[NUC] = 0.013. Simulation studies indicated that the low levels of nuclear differentiation were not the result of limited power because of low levels of polymorphism. These findings, supported by palaeodistribution modelling and mismatch distribution analysis, are consistent with expansion of R. octopus from a single, limited refugium after the Last Glacial Maximum, followed by subsequent isolation, and that the discrepancy between the mitochondrial and nuclear markers is a result of the nuclear loci taking longer to reach mutation–drift equilibrium following the expansion as a result of their four-fold larger effective population size. The populations studied are probably not well connected via gene flow, and thus genetically as well as geographically distinct, although our findings also highlight the need to use a combination of organellar and nuclear markers to enable a more complete understanding of population demography and structure, particularly for species with large effective population sizes.

AN ADSORBATE-STABILIZED VACANCY STRUCTURE FOR CU ON W(100) - A SURFACE ALLOY

Deposition of 0.5 ML of Cu on W(100) leads to the formation of a sharp c(2 x 2) structure when the surface is annealed at 800 K. A LEED intensity analysis reveals that the Cu atoms are adsorbed displacively into W sites, forming an ordered 2D surface alloy. Due to the lattice mismatch between copper and tungsten, a substantial buckling of the first layer of the alloy is also observed. The clean, bulk terminated W(100) surface is only just stable relative to the c(2 x 2) vacancy covered W(100) surface. This relative stability of the vacancy structure explains the driving force behind the formation of this alloy.

The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab

Targeting angiogenesis through inhibition of the vascular endothelial growth factor (VEGF) pathway has been successful in the treatment of late stage colorectal cancer. However, not all patients benefit from inhibition of VEGF. Ras status is a powerful biomarker for response to anti-epidermal growth factor receptor therapy; however, an appropriate biomarker for response to anti-VEGF therapy is yet to be identified. VEGF and its receptors, FLT1 and KDR, play a crucial role in colon cancer progression; individually, these factors have been shown to be prognostic in colon cancer; however, expression of none of these factors alone was predictive of tumor response to anti-VEGF therapy. In the present study, we analyzed the expression levels of VEGFA, FLT1, and KDR in two independent colon cancer datasets and found that high expression levels of all three factors afforded a very poor prognosis. The observation was further confirmed in another independent colon cancer dataset, wherein high levels of expression of this three-gene signature was predictive of poor prognosis in patients with proficient mismatch repair a wild-type KRas status, or mutant p53 status. Most importantly, this signature also predicted tumor response to bevacizumab, an antibody targeting VEGFA, in a cohort of bevacizumab-treated patients. Since bevacizumab has been proven to be an important drug in the treatment of advanced stage colon cancer, our results suggest that the three-gene signature approach is valuable in terms of its prognostic value, and that it should be further evaluated in a prospective clinical trial to investigate its predictive value to anti-VEGF treatment.

Abstract 1905: Defining a therapeutic classification of breast cancer by actionable targets

Breast cancer remains a frequent cause of female cancer death despite the great strides in elucidation of biological subtypes and their reported clinical and prognostic significance. We have defined a general cohort of breast cancers in terms of putative actionable targets, involving growth and proliferative factors, the cell cycle, and apoptotic pathways, both as single biomarkers across a general cohort and within intrinsic molecular subtypes.

We identified 293 patients treated with adjuvant chemotherapy. Additional hormonal therapy and trastuzumab was administered depending on hormonal and HER2 status respectively. We performed immunohistochemistry for ER, PR, HER2, MM1, CK5/6, p53, TOP2A, EGFR, IGF1R, PTEN, p-mTOR and e-cadherin. The cohort was classified into luminal (62%) and non-luminal (38%) tumors as well as luminal A (27%), luminal B HER2 negative (22%) and positive (12%), HER2 enriched (14%) and triple negative (25%). Patients with luminal tumors and co-overexpression of TOP2A or IGF1R loss displayed worse overall survival (p=0.0251 and p=0.0008 respectively). Non-luminal tumors had much greater heterogeneous expression profiles with no individual markers of prognostic significance. Non-luminal tumors were characterised by EGFR and TOP2A overexpression, IGF1R, PTEN and p-mTOR negativity and extreme p53 expression.

Our results indicate that only a minority of intrinsic subtype tumors purely express single novel actionable targets. This lack of pure biomarker expression is particular prevalent in the triple negative subgroup and may allude to the mechanism of targeted therapy inaction and myriad disappointing trial results. Utilising a combinatorial biomarker approach may enhance studies of targeted therapies providing additional information during design and patient selection while also helping decipher negative trial results.

“It’s very complicated”: a qualitative study of medicines management in intermediate care facilities in Northern Ireland

Background: Intermediate care (IC) describes a range of services targeted at older people, aimed at preventing unnecessary hospitalisation, promoting faster recovery from illness and maximising independence. Older people are at increased risk of medication-related adverse events, but little is known about the provision of medicines management services in IC facilities. This study aimed to describe the current provision of medicines management services in IC facilities in Northern Ireland (NI) and to explore healthcare workers' (HCWs) and patients' views of, and attitudes towards these services and the IC concept. 

Methods: Semi-structured interviews were conducted, recorded, transcribed verbatim and analysed using a constant comparative approach with HCWs and patients from IC facilities in NI. 

Results: Interviews were conducted with 25 HCWs and 18 patients from 12 IC facilities in NI. Three themes were identified: 'concept and reality', 'setting and supply' and 'responsibility and review'. A mismatch between the concept of IC and the reality was evident. The IC facility setting dictated prescribing responsibilities and the supply of medicines, presenting challenges for HCWs. A lack of a standardised approach to responsibility for the provision of medicines management services including clinical review was identified. Whilst pharmacists were not considered part of the multidisciplinary team, most HCWs recognised a need for their input. Medicines management was not a concern for the majority of IC patients. 

Conclusions: Medicines management services are not integral to IC and medicine-related challenges are frequently encountered. Integration of pharmacists into the multidisciplinary team could potentially improve medicines management in IC.

Robust bimodal person identification using face and speech with limited training data and corruption of both modalities

This paper presents a novel method of audio-visual fusion for person identification where both the speech and facial modalities may be corrupted, and there is a lack of prior knowledge about the corruption. Furthermore, we assume there is a limited amount of training data for each modality (e.g., a short training speech segment and a single training facial image for each person). A new representation and a modified cosine similarity are introduced for combining and comparing bimodal features with limited training data as well as vastly differing data rates and feature sizes. Optimal feature selection and multicondition training are used to reduce the mismatch between training and testing, thereby making the system robust to unknown bimodal corruption. Experiments have been carried out on a bimodal data set created from the SPIDRE and AR databases with variable noise corruption of speech and occlusion in the face images. The new method has demonstrated improved recognition accuracy.

Multiloop robust H∞ control design based on the dynamic PLS approach to chemical processes

In this paper, a multiloop robust control strategy is proposed based on H∞ control and a partial least squares (PLS) model (H∞_PLS) for multivariable chemical processes. It is developed especially for multivariable systems in ill-conditioned plants and non-square systems. The advantage of PLS is to extract the strongest relationship between the input and the output variables in the reduced space of the latent variable model rather than in the original space of the highly dimensional variables. Without conventional decouplers, the dynamic PLS framework automatically decomposes the MIMO process into multiple single-loop systems in the PLS subspace so that the controller design can be simplified. Since plant/model mismatch is almost inevitable in practical applications, to enhance the robustness of this control system, the controllers based on the H∞ mixed sensitivity problem are designed in the PLS latent subspace. The feasibility and the effectiveness of the proposed approach are illustrated by the simulation results of a distillation column and a mixing tank process. Comparisons between H∞_PLS control and conventional individual control (either H∞ control or PLS control only) are also made

Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant

Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.