Measure for measure: new ways of looking at the long-term performance of firms

The need for sustainable long-term performance is an expectation driving the actions of those at the top of organisations. Yet there are few illusions about just how difficult that is to achieve – nor is it easy to determine precisely what should be measured and how

Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS Guidelines: the EVIDENCE-PAH UK study

BACKGROUND AND AIMS: Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2 WU or lower, at rest. The ESC/ERS guidelines have recently been updated to reflect this. There is limited published data on the nature of these newly defined populations (mPAP 21-24 mmHg and PVR >2-≤3 WU) and the role of comorbidity in determining their natural history. With the change in guidelines, there is a need to understand this population and the impact of the ESC/ERS guidelines in greater detail. METHODS: A retrospective nationwide evaluation of the role of pulmonary haemodynamics and comorbidity in predicting survival among patients referred to the UK pulmonary hypertension (PH) centres between 2009 and 2017. In total, 2929 patients were included in the study. Patients were stratified by mPAP ( 2-≤3 WU, and >3 WU), with 968 (33.0%) in the mPAP 2-≤3WU) was lower than among those with normal pressures (mPAP <21 mmHg) and normal PVR (PVR ≤ 2WU) independent of comorbid lung and heart disease [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.14-1.61, P = .0004 for mPAP vs. HR 1.28, 95% CI 1.10-1.49, P = .0012 for PVR]. Among patients with mildly elevated mPAP, a mildly elevated PVR remained an independent predictor of survival when adjusted for comorbid lung and heart disease (HR 1.33, 95% CI 1.01-1.75, P = .042 vs. HR 1.4, 95% CI 1.06-1.86, P = .019). 68.2% of patients with a mPAP 21-24 mmHg had evidence of underlying heart or lung disease. Patients with mildly abnormal haemodynamics were not more symptomatic than patients with normal haemodynamics. Excluding patients with heart and lung disease, connective tissue disease was associated with a poorer survival among those with PH. In this subpopulation evaluating those with a mPAP of 21-24 mmHg, survival curves only diverged after 5 years. CONCLUSIONS: This study supports the change in diagnostic category of the ESC/ERS guidelines in a PH population. The newly included patients have an increased mortality independent of significant lung or heart disease. The majority of patients in this new category have underlying heart or lung disease rather than an isolated pulmonary vasculopathy. Mortality is higher if comorbidity is present. Rigorous phenotyping will be pivotal to determine which patients are at risk of progressive vasculopathic disease and in whom surveillance and recruitment to studies may be of benefit. This study provides an insight into the population defined by the new guidelines

A Spectral Line Survey of Selected 3 mm Bands Toward Sagittarius B2(N-LMH) Using the NRAO 12 Meter Radio Telescope and the BIMA Array I. The Observational Data

We have initiated a spectral line survey, at a wavelength of 3 millimeters, toward the hot molecular core Sagittarius B2(N-LMH). This is the first spectral line survey of the Sgr B2(N) region utilizing data from both an interferometer (BIMA Array) and a single-element radio telescope (NRAO 12 meter). In this survey, covering 3.6 GHz in bandwidth, we detected 218 lines (97 identified molecular transitions, 1 recombination line, and 120 unidentified transitions). This yields a spectral line density (lines per 100 MHz) of 6.06, which is much larger than any previous 3 mm line survey. We also present maps from the BIMA Array that indicate that most highly saturated species (3 or more H atoms) are products of grain chemistry or warm gas phase chemistry. Due to the nature of this survey we are able to probe each spectral line on multiple spatial scales, yielding information that could not be obtained by either instrument alone.Comment: 35 pages, 15 figures, to be published in The Astrophysical Journa

Common and low Frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients

A discrete choice experiment to explore patients’ willingness to risk disease relapse from treatment withdrawal in psoriatic arthritis

The objective of this study is to assess patient preferences for treatment-related benefits and risk of disease relapse in the management of low disease states of psoriatic arthritis (PsA). Focus groups with patients and a literature review were undertaken to determine the characteristics of treatment and symptoms of PsA important to patients. Patient preferences were assessed using a discrete choice experiment which compared hypothetical treatment profiles of the risk and benefits of treatment withdrawal. The risk outcome included increased risk of disease relapse, while benefit outcomes included reduced sickness/nausea from medication and changes in health-related quality of life. Each patient completed 12 choice sets comparing treatment profiles. Preference weights were estimated using a logic regression model, and the maximum acceptable risk in disease relapse for a given improvement in benefit outcomes was elicited. Final sample included 136 patients. Respondents attached the greatest importance to eliminating severe side effects of sickness/nausea and the least importance to a change in risk of relapse. Respondents were willing to accept an increase in the risk of relapse of 32.6 % in order to eliminate the side effects of sickness/nausea. For improvements in health status, the maximum acceptable risk in relapse was comparable to a movement from some to no sickness/nausea. The study suggests that patients in low disease states of PsA are willing to accept greater risks of relapse for improvements in side effects of sickness/nausea and overall health status, with the most important benefit attribute being the elimination of severe sickness or nausea

HIV risk behaviors among female IDUs in developing and transitional countries

Abstract Background A number of studies suggest females may be more likely to engage in injection and sex risk behavior than males. Most data on gender differences come from industrialized countries, so data are needed in developing countries to determine how well gender differences generalize to these understudied regions. Methods Between 1999 and 2003, 2512 male and 672 female current injection drug users (IDUs) were surveyed in ten sites in developing countries around the world (Nairobi, Beijing, Hanoi, Kharkiv, Minsk, St. Petersburg, Bogotá, Gran Rosario, Rio, and Santos). The survey included a variety of questions about demographics, injecting practices and sexual behavior. Results Females were more likely to engage in risk behaviors in the context of a sexual relationship with a primary partner while males were more likely to engage in risk behaviors in the context of close friendships and casual sexual relationships. After controlling for injection frequency, and years injecting, these gender differences were fairly consistent across sites. Conclusion Gender differences in risk depend on the relational contexts in which risk behaviors occur. The fact that female and male risk behavior often occurs in different relational contexts suggests that different kinds of prevention interventions which are sensitive to these contexts may be necessary.</p

Novel Bound States Treatment of the Two Dimensional Schrodinger Equation with Pseudocentral Plus Multiparameter Noncentral Potential

By converting the rectangular basis potential V(x,y) into the form as V(r)+V(r, phi) described by the pseudo central plus noncentral potential, particular solutions of the two dimensional Schrodinger equation in plane-polar coordinates have been carried out through the analytic approaching technique of the Nikiforov and Uvarov (NUT). Both the exact bound state energy spectra and the corresponding bound state wavefunctions of the complete system are determined explicitly and in closed forms. Our presented results are identical to those of the previous works and they may also be useful for investigation and analysis of structural characteristics in a variety of quantum systemsComment: Published, 16 page