Influence of prior activity (warm-up) and inspiratory muscle training upon between- and within-day reliability of maximal inspiratory pressure measurement

This is the post-print version of the article. The official published version can be obtained from the link below.BACKGROUND: A specific inspiratory muscle ‘warm-up’ (IWU) prior to assessment of maximal inspiratory mouth pressure (PImax) may reduce the number of measurements required to obtain reproducible, representative estimates of PImax. The influence of inspiratory muscle training (IMT) upon this phenomenon is unknown. OBJECTIVE: Compare the impact of an IWU on the between- and within-day reliability of PImax before and after IMT. METHOD: Eight participants were assessed on 4 separate occasions: 2 trials preceded IMT and 2 followed it. At each assessment, the highest of 3 initial efforts was recorded as the pre-IWU value (PI). The highest of 9 subsequent efforts that followed 2 sets of 30 breaths at 40% PI was recorded as PImax. Following 4 weeks of IMT, the trials were repeated. RESULTS: IWU increased PI by 11–17% (p ≤ 0.01), irrespective of IMT status. After IWU, 5–6 efforts were required to determine PImax, irrespective of IMT status. PImax was similar between the 2 trials before IMT and the 2 trials after IMT (p ≥ 0.05), and was 21% higher after IMT (p ≤ 0.01). The coefficient of variation was excellent before and after IWU, both before (1.9 and 0.6%, respectively) and after IMT (1.1 and 0.3%, respectively). Limits of agreement and sample sizes for effect sizes ≤10% were substantially smaller after IWU in all trials. CONCLUSIONS: (1) IWU enhances the between-day reliability of PImax measurement, and this is unaffected by IMT, and (2) judgements regarding acceptability in relation to PImax reliability should be made in relation to analytical goals and we present data to facilitate this

Optimising workplace interventions for health and wellbeing: a commentary on the limitations of the public health perspective within the workplace health arena [forthcoming]

Purpose: This paper discusses contemporary approaches to workplace health and well-being, articulating key differences in the intervention architecture between public and workplace health contexts and implications for intervention design. Approach: Contemporary practice is discussed in light of calls for a paradigm shift in occupational health from a treatment orientation to an holistic approach focused on mitigation of the causes of ill health and the promotion of well-being. In practice, relatively few organizations have or seem able to engage with a broader perspective that encompasses challenges to health and well-being associated with contextual organizational drivers, e.g. job design/role, workload, systems of reward, leadership style and the underpinning climate. Drawing upon insights from public health and the workplace safety tradition, the scope for broadening the perspective on intervention (in terms of vectors of harm addressed, theory of change and intervention logic) is discussed. Findings: There are important differences in scope and options for intervention between public health and workplace health contexts. While there is scope to emulate public health practice, this should not constrain thinking over intervention opinions. Increased awareness of these key differences within work organizations, and an evidence-based epidemiological approach to learning has the potential to strengthen and broaden the approach to workplace health and well-being management. Originality/Value: We argue that approaches to workplace well-being interventions that selectively cross-fertilise and adapt elements of public health interventions offer promise for realising a broader change agenda and for building inherently healthy workplaces

Extramedullary Plasmacytoma of Soft Tissues and Gingiva

Extramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm of soft tissue without bone marrow involvement or other systemic characteristics of multiple myeloma. It accounts for 3% of all plasma cell tumors. Multiple extramedullary plasmacytoma is defined when there is more than one extramedullary tumor of clonal plasma cells and such presentation has not been described earlier. We report such rare case of multiple extramedullary plasmacytoma involving multiple soft tissues in chest, abdomen, mandible, maxilla, and gingiva

Engineering orthogonal dual transcription factors for multi-input synthetic promoters

Synthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage λ cI variants and multi-input promoter architectures. Our toolkit contains 12 TFs, flexibly operating as activators, repressors, dual activator–repressors or dual repressor–repressors, on up to 270 synthetic promoters. To engineer non cross-reacting cI variants, we design a new M13 phagemid-based system for the directed evolution of biomolecules. Because cI is used in so many synthetic biology projects, the new set of variants will easily slot into the existing projects of other groups, greatly expanding current engineering capacities

The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle

Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-temporal regulation of replication initiation remains enigmatic. To unveil the molecular underpinnings, we studied the human lamin B2 origin that spatially overlaps with TIMM 13 promoter. We observed an early G1-specific occupancy of c-Myc that facilitated the loading of mini chromosome maintenance protein (MCM) complex during subsequent mid-G1 phase rather stimulating TIMM 13 gene expression. Investigations on the Myc-induced downstream events suggested a direct interaction between c-Myc and histone methyltransferase mixed-lineage leukemia 1 that imparted histone H3K4me3 mark essential for both recruitment of acetylase complex HBO1 and hyperacetylation of histone H4. Contemporaneously, the nucleosome remodeling promoted the loading of MCM proteins at the origin. These chromatin modifications were under the tight control of active demethylation of E-box as evident from methylation profiling. The active demethylation was mediated by the Ten-eleven translocation (TET)-thymine DNA glycosylase-base excision repair (BER) pathway, which facilitated spatio-temporal occupancy of Myc. Intriguingly, the genome-wide 43% occurrence of E-box among the human origins could support our hypothesis that epigenetic control of E-box could be a molecular switch for the licensing of early replicating origins

Kinetic study of crystallisation of sol-gel derived calcia-alumina binary compounds

In-situ High Temperature X-ray Diffraction (HTXRD) and Differential Scanning Calorimetric (DSC) studies were performed on a sol-gel derived binary compound of a calcia-alumina (C12A7) system consisting of calcium oxide (CaO) and aluminium oxide (Al2O3) in a ratio of 12:7 for in situ investigation into the phase transformations under progressively increasing thermal activation from roomerature to 1200 °C. The crystallisation of amorphous samples formulated at roomerature on magnesium oxide (MgO) single crystal (100) substrates was found to be complete on heat treatment at 1100 °C for 3 h. This observation was further supported by independent Fourier Transform Infrared (FTIR) and Raman Spectroscopies. Values of 348 kJ/mol and 375 kJ/mol were estimated from Kissinger plots for activation energies of crystallisation of CaO and Al2O3 constituents, respectively

Liver transplantation

Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients showed that HCC recurrence rates were halved if a minimization of CNIs was applied within the first month after liver transplant. With mammalian target of rapamycin (mTOR) inhibitors as approved immunosuppressants for liver transplant patients, pooled data from several retrospective studies have suggested their possible benefit for reducing HCC recurrence. Summary: Randomized controlled trials with sufficiently long follow-up are needed to evaluate the influence of different immunosuppression protocols in preventing malignancy after LT. Currently, early minimization of CNIs with or without mTOR inhibitors or mycophenolate seems a rational strategy for patients with risk factors for de-novo malignancy or recurrence of HCC after liver transplant. A deeper understanding of the immunological pathways of rejection and cancer would allow for designing more specific and safer drugs, and thus to prevent cancer after liver transplant

Dual-layer network representation exploiting information characterization

In this paper, a logical dual-layer representation approach is proposed to facilitate the analysis of directed and weighted complex networks. Unlike the single logical layer structure, which was widely used for the directed and weighted flow graph, the proposed approach replaces the single layer with a dual-layer structure, which introduces a provider layer and a requester layer. The new structure provides the characterization of the nodes by the information, which they provide to and they request from the network. Its features are explained and its implementation and visualization are also detailed. We also design two clustering methods with different strategies respectively, which provide the analysis from different points of view. The effectiveness of the proposed approach is demonstrated using a simplified example. By comparing the graph layout with the conventional directed graph, the new dual-layer representation reveals deeper insight into the complex networks and provides more opportunities for versatile clustering analysis.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

Local Stellar Kinematics from RAVE data - VII. Metallicity Gradients from Red Clump Stars

We investigate the Milky Way Galaxy's radial and vertical metallicity gradients using a sample of 47,406 red clump stars from the RAVE DR4. This sample is more than twice the size of the largest sample in the literature investigating radial and vertical metallicity gradients. The absolute magnitude of Groenewegen (2008) is used to determine distances to our sample stars. The resulting distances agree with the RAVE DR4 distances Binney et al. (2014) of the same stars. Our photometric method also provides distances to 6185 stars that are not assigned a distance in RAVE DR4. The metallicity gradients are calculated with their current orbital positions ($R_{gc}$ and $Z$) and with their orbital properties (mean Galactocentric distance, $R_{m}$ and $z_{max}$), as a function of the distance to the Galactic plane: d[Fe/H]/d$R_{gc}=$-$0.047\pm0.003$ dex/kpc for $0\leq |Z|\leq0.5$ kpc and d[Fe/H]/d$R_m=$-$0.025\pm0.002$ dex/kpc for $0\leq z_{max}\leq0.5$ kpc. This reaffirms the radial metallicity gradient in the thin disc but highlights that gradients are sensitive to the selection effects caused by the difference between $R_{gc}$ and $R_{m}$. The radial gradient is flat in the distance interval 0.5-1 kpc from the plane and then becomes positive greater than 1 kpc from the plane. The radial metallicity gradients are also eccentricity dependent. We showed that d[Fe/H]/d$R_m=$-$0.089\pm0.010$, -$0.073\pm0.007$, -$0.053\pm0.004$ and -$0.044\pm0.002$ dex/kpc for $e_p\leq0.05$, $e_p\leq0.07$, $e_p\leq0.10$ and $e_p\leq0.20$ sub-samples, respectively, in the distance interval $0\leq z_{max}\leq0.5$ kpc. Similar trend is found for vertical metallicity gradients. Both the radial and vertical metallicity gradients are found to become shallower as the eccentricity of the sample increases. These findings can be used to constrain different formation scenarios of the thick and thin discs.Comment: 18 pages, including 16 figures and 6 tables, accepted for publication in PAS