Cut-off values to evaluate exercise-induced asthma in eucapnic voluntary hyperventilation test for children

Background and Aim The eucapnic voluntary hyperventilation (EVH) testing is a diagnostic tool for diagnostics of exercise-induced bronchoconstriction; while the testing has become more common among children, data on the test's feasibility among children remain limited. Our aim was to investigate EVH testing feasibility among children, diagnostic testing cut-off values, and which factors affect testing outcomes. Methods We recruited 134 patients aged 10-16 years with a history of exercise-induced dyspnoea and 100 healthy control children to undergo 6-min EVH testing. Testing feasibility was assessed by the children's ability to achieve >= 70% of the target minute ventilation of 30 times forced expiratory volume in 1 s (FEV1). Bronchoconstriction was assessed as a minimum of 8%, 10%, 12%, 15% or 20% fall in FEV1. Patient characteristics were correlated with EVH outcomes. Results Overall, 98% of the children reached >= 70%, 88% reached >= 80%, 79% reached >= 90% and 62% reached >= 100% of target ventilation in EVH testing; of children with a history of exercise-induced dyspnoea, the decline percentages were as follows: 24% (>= 8% fall), 17% (>= 10% fall), 10% (>= 12% fall), 6% (>= 15% fall) and 5% (>= 20% fall) in FEV1, compared to 11%, 4%, 3%, 1% and 0% among the healthy controls, respectively. Healthy controls and boys performed testing at higher ventilation rates (p < .05). Conclusion Eucapnic voluntary hyperventilation testing is feasible among children aged 10-16 years and has diagnostic value in evaluating exercise-induced dyspnoea among children. A minimum 10% fall in FEV1 is a good diagnostic cut-off value. Disease status appears to be important covariates

Local biases drive, but do not determine, the perception of illusory trajectories

When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception

Local biases drive, but do not determine, the perception of illusory trajectories

When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception

Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers

Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really beneficial. However, the development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly associated with the development of recurrence (P= 0.01) and indicated poor survival in patients of Dukes' classes B and C, in which most recurrences (82%) occurred. An increased rate of tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies. © 1999 Cancer Research Campaig

Association between fixation type and revision risk in total knee arthroplasty patients aged 65 years and older: a cohort study of 265,877 patients from the Nordic Arthroplasty Register Association 2000-2016

Background and purpose - The population of the Nordic countries is aging and the number of elderly patients undergoing total knee arthroplasty (TKA) is also expected to increase. Reliable fixation methods are essential to avoid revisions. We compared the survival of different TKA fixation concepts with cemented fixation as the gold standard. Patients and methods - We used data from the Nordic Arthroplasty Register Association (NARA) database of 265,877 unconstrained TKAs performed for patients aged ≥ 65 years with primary knee osteoarthritis between 2000 and 2016. Kaplan-Meier (KM) survival analysis with 95% confidence intervals (CI) and the Cox multiple-regression model were used to compare the revision risk of the fixation methods. Results - Cemented fixation was used in 243,166 cases, uncemented in 8,000, hybrid (uncemented femur with cemented tibia) in 14,248, and inverse hybrid (cemented femur with uncemented tibia) fixation in 463 cases. The 10-year KM survivorship (95% CI) of cemented TKAs was 96% (96 - 97), uncemented 94% (94 - 95), hybrid 96% (96 - 96), and inverse hybrid 96% (94 - 99), respectively. Uncemented TKA was associated with increased risk of revision compared with the cemented TKA; the adjusted hazard ratio was 1.3 (95% CI 1.1 - 1.4). Interpretation - Cemented, hybrid, and inverse hybrid TKAs showed 10-year survival rates exceeding 95%. Uncemented fixation was associated with an increased risk of revision in comparison with cemented fixation. As both hybrid and inverse hybrid fixation were used in only a limited number of TKAs, indicating possibility of selection bias in their favor, cemented TKA still remains the gold standard, as it works reliably in the hands of many

How do MNC R&amp;D laboratory roles affect employee international assignments?

Research and development (R&#38;D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&#38;D laboratories in which these employees work on the international assignments they undertake. We categorise R&#38;D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&#38;D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&#38;D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state, but direct pharmacological inhibition of transcription factors has so far proven difficult. However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates, including cyclin-dependent kinases (CDKs). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.National Institutes of Health (U.S.) (Grant HG002668)National Institutes of Health (U.S.) (Grant CA109901