Explore the vast range of titles available.

28 Certainty and ease of application are the hallmarks of the nerve center test.29 As the Seventh Circuit explained: Since certainty of jurisdiction is a desideratum too - the parties ought to know definitely what court they belong in, and not face the prospect that their litigation may be set at naught because they made a wrong guess about jurisdiction - this circuit has long used a simple nerve center test for principal place of business.30 The corporation's nerve center is ordinarily found where the corporation has its headquarters.

Objective To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status.Design Prospective, randomised controlled trial.Setting An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom.Participants 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193).Main outcome measures The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome.Interventions Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package.Results Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year.Conclusion Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months. Mortality at 12 months was higher in the intervention group. The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.Trial registration Current Controlled Trials ISRCTN05557928.

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.

Animals live in a colorful world, but we rarely stop to think about how this color is produced and perceived, or how it evolved. Cuthill et al. review how color is used for social signals between individual animals and how it affects interactions with parasites, predators, and the physical environment. New approaches are elucidating aspects of animal coloration, from the requirements for complex cognition and perception mechanisms to the evolutionary dynamics surrounding its development and diversification. Science , this issue p. eaan0221 Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field.

In the solar system, the planets' compositions vary with orbital distance, with rocky planets in close orbits and lower-density gas giants in wider orbits. The detection of close-in giant planets around other stars was the first clue that this pattern is not universal and that planets' orbits can change substantially after their formation. Here, we report another violation of the orbit-composition pattern: two planets orbiting the same star with orbital distances differing by only 10% and densities differing by a factor of 8. One planet is likely a rocky \"super-Earth,\" whereas the other is more akin to Neptune. These planets are 20 times more closely spaced and have a larger density contrast than any adjacent pair of planets in the solar system.

Hospitalization represents a major event for the patient with chronic respiratory disease. There is a high risk of readmission, which over the longer term may be related more closely to the underlying condition of the patient, such as skeletal muscle dysfunction. We assessed the risk of hospital readmission at 1 year, including measures of lower limb muscle as part of a larger clinical trial. Patients hospitalized with an exacerbation of chronic respiratory disease underwent measures of muscle function including quadriceps ultrasound. Independent factors influencing time to hospital readmission or death were identified. Patients were classified into four quartiles based on quadriceps size and compared. One hundred and ninety-one patients (mean age, 71.6 [SD, 9.1] yr) were recruited. One hundred and thirty (68%) were either readmitted or died. Factors associated with readmission or death were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.08; P = 0.015), Medical Research Council (MRC) dyspnea grade (OR, 4.57; 95% CI, 2.62-7.95; P < 0.001), home oxygen use (OR, 12.4; 95% CI, 4.53-33.77; P < 0.001), quadriceps (rectus femoris) cross-sectional area (Qcsa) (OR, 0.34; 95% CI, 0.17-0.65; P = 0.001), and hospitalization in the previous year (OR, 4.82; 95% CI, 2.42-9.58; P < 0.001). In the multivariate analyses, home oxygen use (OR, 4.80; 95% CI, 1.68-13.69; P = 0.003), MRC dyspnea grade (OR, 2.57; 95% CI, 1.44-4.59; P = 0.001), Qcsa (OR, 0.46; 95% CI, 0.22-0.95; P = 0.035), and previous hospitalization (OR, 3.04; 95% CI, 1.47-6.29; P = 0.003) were independently associated with readmission or death. Patients with the smallest muscle spent more days in hospital than those with largest muscle (28.1 [SD, 33.9] vs. 12.2 [SD, 23.5] d; P = 0.007). Smaller quadriceps muscle size, as measured by ultrasound in the acute care setting, is an independent risk factor for unscheduled readmission or death, which may have value both in clinical practice and for risk stratification.

An approach is demonstrated to obtain, in a sample- and time-efficient manner, multiple dose-resolved crystal structures from room-temperature protein microcrystals using identical fixed-target supports at both synchrotrons and X-ray free-electron lasers (XFELs). This approach allows direct comparison of dose-resolved serial synchrotron and damage-free XFEL serial femtosecond crystallography structures of radiation-sensitive proteins. Specifically, serial synchrotron structures of a heme peroxidase enzyme reveal that X-ray induced changes occur at far lower doses than those at which diffraction quality is compromised (the Garman limit), consistent with previous studies on the reduction of heme proteins by low X-ray doses. In these structures, a functionally relevant bond length is shown to vary rapidly as a function of absorbed dose, with all room-temperature synchrotron structures exhibiting linear deformation of the active site compared with the XFEL structure. It is demonstrated that extrapolation of dose-dependent synchrotron structures to zero dose can closely approximate the damage-free XFEL structure. This approach is widely applicable to any protein where the crystal structure is altered by the synchrotron X-ray beam and provides a solution to the urgent requirement to determine intact structures of such proteins in a high-throughput and accessible manner.

ObjectiveTo develop an Overall Pediatric Health Standard Set (OPH-SS) of outcome measures that captures what matters to young people and their families and recognising the biopsychosocial aspects of health for all children and adolescents regardless of health condition.DesignA modified Delphi process.SettingThe International Consortium for Health Outcomes Measurement convened an international Working Group (WG) comprised of 23 international experts from 12 countries in the field of paediatrics, family medicine, psychometrics as well as patient advisors. The WG participated in 11 video-conferences, through a modified Delphi process and 9 surveys between March 2018 and January 2020 consensus was reached on a final recommended health outcome standard set. By a literature review conducted in March 2018, 1136 articles were screened for clinician and patient-reported or proxy-reported outcomes. Further, 4315 clinical trials and 12 paediatric health surveys were scanned. Between November 2019 and January 2020, the final standard set was endorsed by a patient validation (n=270) and a health professional (n=51) survey.ResultsFrom a total of 63 identified outcomes, consensus was formed on a standard set of outcome measures that comprises 10 patient-reported outcomes, 5 clinician-reported measures, and 6 case-mix variables. The four developmental age-specific packages (ie, 0–5, 6–12, 13–17, 18–24 years) include either five or six measures with an average time for completion of 20 min.ConclusionsThe OPH-SS is a starting point to drive value-based paediatric healthcare delivery from a global perspective for enhancing child and adolescent physical health and psychosocial well-being.

Stellar data from the Kepler spacecraft are used to infer the existence of a sub-Mercury-sized exoplanet, the smallest yet discovered, in orbit around a Sun-like star. Mercury-like exoplanets in Kepler's sights When the Kepler spacecraft was launched in 2009 its brief was to search for rocky planets around Sun-like host stars in our Galaxy. Many of the hundreds of known exoplanets are large 'hot Jupiters' close-in to their stars. Last year it became possible to detect Earth-sized exoplanets, and now comes the discovery of a rocky planet significantly smaller than Mercury. Kepler-37b is orbiting the Sun-like star Kepler-37 in a system with at least two other planets. It is similar to our Moon in size and is likely to resemble Mercury: rocky, no atmosphere and no water. Since the discovery of the first exoplanets 1 , 2 , it has been known that other planetary systems can look quite unlike our own 3 . Until fairly recently, we have been able to probe only the upper range of the planet size distribution 4 , 5 , and, since last year, to detect planets that are the size of Earth 6 or somewhat smaller 7 . Hitherto, no planets have been found that are smaller than those we see in the Solar System. Here we report a planet significantly smaller than Mercury 8 . This tiny planet is the innermost of three that orbit the Sun-like host star, which we have designated Kepler-37. Owing to its extremely small size, similar to that of the Moon, and highly irradiated surface, the planet, Kepler-37b, is probably rocky with no atmosphere or water, similar to Mercury.

Background When evaluating the outcomes of treatment in paediatric endocrinology, the health-related quality of life (HrQoL) of the child is to be taken into consideration. Since few self–reported HrQoL instruments exist for children with diagnosed short stature (dSS), the objective of this study was to develop and psychometrically test a targeted HrQoL instrument for use in multinational clinical research. Methods The target population were short stature (height < −2 SDS) children and adolescents (age 8–12 and 13–18 years) with a diagnosis of growth hormone deficiency (GHD) or idiopathic short stature (ISS), differing in growth hormone treatment status. Focus group discussions for concept and item generation, piloting of the questionnaire with cognitive debriefing, and instrument field testing with a retest were conducted simultaneously in five countries. After qualitative and preliminary quantitative analyses, psychometric testing of field test data in terms of reliability and validity including confirmatory factor analyses (CFA) was performed. Results Following item generation from focus group discussions, 124 items were included in a pilot test with a cognitive debriefing exercise providing preliminary feedback on item and domain operating characteristics. A field test with 268 participants showed high internal consistency reliabilities (alpha 0.82 – 0.95), good correlations with generic measures (up to r = .58), significant known group differences (e.g. in height: F = 32, df 244, p < 0.001) and an acceptable CFA model fit suggesting construct validity of the three-domain core structure with 22 items, supplemented by three mediator domains with 28 items. Conclusions The QoLISSY questionnaire is a promising step forward in assessing the impact of dSS on HrQoL. It is based on items generated from the subjective experience of short stature children referred for endocrine investigation, is validated for use in five languages and it is easy to administer in clinical and research settings.