Effective Dose 50 method as the Minimal Clinically Important Difference:Evidence from depression trials

OBJECTIVE: Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity. STUDY DESIGN AND SETTINGS: The present analysis used secondary data from two randomised controlled trials for depression (n=1,122) to calibrate the Global Rating of Change with the PHQ-9 and GAD-7. The MCID was defined as a change in scores corresponding to a 50% probability of patients "feeling better", given their baseline severity, referred to as Effective Dose 50 (ED50). RESULTS: MCID estimates depended on baseline severity and ranged from no change for very mild up to 14 points (52%) on the PHQ-9 and up to 10 points (48%) on the GAD-7 for very high severity. The average MCID estimates were 3.7 points (23%) and 3.3 (28%) for the PHQ-9 and GAD-7 respectively. CONCLUSION: The ED50 method generates MCID estimates across the spectrum of baseline severity, offering greater precision but at the cost of greater complexity relative to population average estimates. This has important implications for evaluations of treatments and clinical practice where users can employ these results to tailor the MCID to specific populations according to baseline severities

Integrating omics to characterize eco‐physiological adaptations: How moose diet and metabolism differ across biogeographic zones

1. With accelerated land conversion and global heating at northern latitudes, it becomes crucial to understand, how life histories of animals in extreme environments adapt to these changes. Animals may either adapt by adjusting foraging behavior or through physiological responses, including adjusting their energy metabolism or both. Until now, it has been difficult to study such adaptations in free‐ranging animals due to methodological constraints that prevent extensive spatiotemporal coverage of ecological and physiological data. 2. Through a novel approach of combining DNA‐metabarcoding and nuclear magnetic resonance (NMR)‐based metabolomics, we aim to elucidate the links between diets and metabolism in Scandinavian moose Alces alces over three biogeographic zones using a unique dataset of 265 marked individuals. 3. Based on 17 diet items, we identified four different classes of diet types that match browse species availability in respective ecoregions in northern Sweden. Individuals in the boreal zone consumed predominantly pine and had the least diverse diets, while individuals with highest diet diversity occurred in the coastal areas. Males exhibited lower average diet diversity than females. 4. We identified several molecular markers indicating metabolic constraints linked to diet constraints in terms of food availability during winter. While animals consuming pine had higher lipid, phospocholine, and glycerophosphocholine concentrations in their serum than other diet types, birch‐ and willow/aspen‐rich diets exhibit elevated concentrations of several amino acids. The individuals with highest diet diversity had increased levels of ketone bodies, indicating extensive periods of starvation for these individuals. 5. Our results show how the adaptive capacity of moose at the eco‐physiological level varies over a large eco‐geographic scale and how it responds to land use pressures. In light of extensive ongoing climate and land use changes, these findings pave the way for future scenario building for animal adaptive capacity

Diversity and composition of tropical butterflies along an Afromontane agricultural gradient in the Jimma Highlands, Ethiopia

Afromontane landscapes are typically characterized by a mosaic of smallholder farms and the biodiversity impacts of these practices will vary in accordance to local management and landscape context. Here, we assess how tropical butterfly diversity is maintained across an agricultural landscape in the Jimma Highlands of Ethiopia. We used transect surveys to sample understory butterfly communities within degraded natural forest, semi-managed coffee forest (SMCF), exotic timber plantations, open woodland, croplands and pasture. Surveys were conducted in 29 one-hectare plots and repeated five times between January and June 2013. We found that natural forest supports higher butterfly diversity than all agricultural plots (measured with Hill's numbers). SMCF and timber plantations retain relatively high abundance and diversity, but these metrics drop off sharply in open woodland, cropland and pasture. SMCF and timber plantations share the majority of their species with natural forest and support an equivalent abundance of forest-dependent species, with no increase in widespread species. There was some incongruence in the responses of families and sub-families, notably that Lycaenidae are strongly associated with open woodland and pasture. Adult butterflies clearly utilize forested agricultural practices such as SMCF and timber plantations, but species diversity declines steeply with distance from natural forest suggesting that earlier life-stages may depend on host plants and/or microclimatic conditions that are lost under agricultural management. From a management perspective, the protection of natural forest remains a priority for tropical butterfly conservation, but understanding functioning of the wider landscape mosaic is important as SMCF and timber plantations may act as habitat corridors that facilitate movement between forest fragments

<i>Spitzer</i> microlens measurement of a massive remnant in a well-separated binary

We report the detection and mass measurement of a binary lens OGLE-2015-BLG-1285La,b, with the more massive component having M1 > 1.35 M⊙ (80% probability). A main-sequence star in this mass range is ruled out by limits on blue light, meaning that a primary in this mass range must be a neutron star (NS) or black hole (BH). The system has a projected separation r⊥ = 6.1 ± 0.4 AU and lies in the Galactic bulge. These measurements are based on the "microlens parallax" effect, i.e., comparing the microlensing light curve as seen from Spitzer, which lay at 1.25 AU projected from Earth, to the light curves from four ground-based surveys, three in the optical and one in the near-infrared. Future adaptive optics imaging of the companion by 30 m class telescopes will yield a much more accurate measurement of the primary mass. This discovery both opens the path and defines the challenges to detecting and characterizing BHs and NSs in wide binaries, with either dark or luminous companions. In particular, we discuss lessons that can be applied to future Spitzer and Kepler K2 microlensing parallax observations

Spitzer Parallax of OGLE-2018-BLG-0596: A Low-mass-ratio Planet around an M Dwarf

We report the discovery of a Spitzer microlensing planet OGLE-2018-BLG-0596Lb, with preferred planet-host mass ratio q ∼ 2 x 10-4. The planetary signal, which is characterized by a short (∼1 day) bump on the rising side of the lensing light curve, was densely covered by ground-based surveys. We find that the signal can be explained by a bright source that fully envelops the planetary caustic, i.e., a Hollywood geometry. Combined with the source proper motion measured from Gaia, the Spitzer satellite parallax measurement makes it possible to precisely constrain the lens physical parameters. The preferred solution, in which the planet perturbs the minor image due to lensing by the host, yields a Uranus-mass planet with a mass of M p = 13.9 +1.6 M ⊕ orbiting a mid M-dwarf with a mass of M h = 0.23 +0.03 M o. There is also a second possible solution that is substantially disfavored but cannot be ruled out, for which the planet perturbs the major image. The latter solution yields M p = 1.2 +0.2 M ⊕ and M h = 0.15 +0.02 M o. By combining the microlensing and Gaia data together with a Galactic model, we find in either case that the lens lies on the near side of the Galactic bulge at a distance D L ∼ 6 +1 kpc. Future adaptive optics observations may decisively resolve the major image/minor image degeneracy

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

The Relationship Between Therapist Effects and Therapy Delivery Factors: Therapy Modality, Dosage, and Non-completion.

To consider the relationships between, therapist variability, therapy modality, therapeutic dose and therapy ending type and assess their effects on the variability of patient outcomes. Multilevel modeling was used to analyse a large sample of routinely collected data. Model residuals identified more and less effective therapists, controlling for case-mix. After controlling for case mix, 5.8 % of the variance in outcome was due to therapists. More sessions generally improved outcomes, by about half a point on the PHQ-9 for each additional session, while non-completion of therapy reduced the amount of pre-post change by six points. Therapy modality had little effect on outcome. Patient and service outcomes may be improved by greater focus on the variability between therapists and in keeping patients in therapy to completion

OGLE-2017-BLG-1038: A Possible Brown-dwarf Binary Revealed by Spitzer Microlensing Parallax

We report the analysis of microlensing event OGLE-2017-BLG-1038, observed by the Optical Gravitational Lensing Experiment, Korean Microlensing Telescope Network, and Spitzer telescopes. The event is caused by a giant source star in the Galactic Bulge passing over a large resonant binary lens caustic. The availability of space-based data allows the full set of physical parameters to be calculated. However, there exists an eightfold degeneracy in the parallax measurement. The four best solutions correspond to very-low-mass binaries near ($M_1 = 170^{+40}_{-50} M_J$ and $M_2 = 110^{+20}_{-30} M_J$), or well below ($M_1 = 22.5^{+0.7}_{-0.4} M_J$ and $M_2 = 13.3^{+0.4}_{-0.3} M_J$) the boundary between stars and brown dwarfs. A conventional analysis, with scaled uncertainties for Spitzer data, implies a very-low-mass brown dwarf binary lens at a distance of 2 kpc. Compensating for systematic Spitzer errors using a Gaussian process model suggests that a higher mass M-dwarf binary at 6 kpc is equally likely. A Bayesian comparison based on a galactic model favors the larger-mass solutions. We demonstrate how this degeneracy can be resolved within the next ten years through infrared adaptive-optics imaging with a 40 m class telescope.Comment: 20 pages, 11 figures, 4 table