Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are ...being used to measure its properties. However, the nature of the Type Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now, new large surveys are bringing about a paradigm shift--we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modelling, breakthroughs in understanding all aspects of these supernovae are finally starting to happen.
Machine learning is used increasingly in clinical care to improve diagnosis, treatment selection, and health system efficiency. Because machine-learning models learn from historically collected data, ...populations that have experienced human and structural biases in the past-called protected groups-are vulnerable to harm by incorrect predictions or withholding of resources. This article describes how model design, biases in data, and the interactions of model predictions with clinicians and patients may exacerbate health care disparities. Rather than simply guarding against these harms passively, machine-learning systems should be used proactively to advance health equity. For that goal to be achieved, principles of distributive justice must be incorporated into model design, deployment, and evaluation. The article describes several technical implementations of distributive justice-specifically those that ensure equality in patient outcomes, performance, and resource allocation-and guides clinicians as to when they should prioritize each principle. Machine learning is providing increasingly sophisticated decision support and population-level monitoring, and it should encode principles of justice to ensure that models benefit all patients.
This review focused on the identification of patient-reported outcome measures (PROMs) used in routine cancer clinical practice, the impact on patient, provider, and system outcomes, and the ...implementation factors influencing uptake.
A scoping review of the published health literature was conducted using empirical databases, namely, Ovid Medline (2003 to September 2013), CINAHL (2003–2013) and PsycINFO (2003–2013). Scoping reviews are systematic literature reviews in a broad topic area that provide relevant and quantified results about the knowledge available on a particular topic and aim to rapidly map and synthesize the evidence to emphasize what is known.
From a total of 2447 unique publications, 30 articles that met eligibility criteria were reviewed. PRO use appears to be acceptable to patients, enables earlier detection of symptoms and may improve communication between clinicians and patients. However, the impact of routine PROMs collection on health outcomes is less clear and high-quality research is still warranted.
PROMs use in routine cancer clinical practice is growing with improvements on essential care processes shown but a number of implementation barriers must still be addressed. The lack of standardization in PROMs used in cancer organizations may make it difficult to use these data for quality monitoring in the future.
Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation ...comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.
The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear ...explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M ). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.
Autoimmune skin diseases are characterized by significant local and systemic inflammation that is largely mediated by the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) ...pathway. Advanced understanding of this pathway has led to the development of targeted inhibitors of Janus kinases (JAKinibs). As a class, JAK inhibitors effectively treat a multitude of hematologic and inflammatory diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. Here we review the evolving data on the role of the JAK-STAT pathway in inflammatory dermatoses and the potential therapeutic benefit of JAK-STAT antagonism.
Spinal muscular atrophy (SMA), a prominent genetic disease of infant mortality, is caused by low levels of survival motor neuron (SMN) protein owing to deletions or mutations of the SMN1 gene. SMN2, ...a nearly identical copy of SMN1 present in humans, cannot compensate for the loss of SMN1 because of predominant skipping of exon 7 during pre-mRNA splicing. With the recent US Food and Drug Administration approval of nusinersen (Spinraza), the potential for correction of SMN2 exon 7 splicing as an SMA therapy has been affirmed. Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School. ISS-N1 has emerged as the model target for testing the therapeutic efficacy of antisense oligonucleotides using different chemistries as well as different mouse models of SMA. Here, we provide a historical account of events that led to the discovery of ISS-N1 and describe the impact of independent validations that raised the profile of ISS-N1 as one of the most potent antisense targets for the treatment of a genetic disease. Recent approval of nusinersen provides a much-needed boost for antisense technology that is just beginning to realize its potential. Beyond treating SMA, the ISS-N1 target offers myriad potentials for perfecting various aspects of the nucleic-acid-based technology for the amelioration of the countless number of pathological conditions.
The 2016 definitions of sepsis included the quick Sepsis-related Organ Failure Assessment (qSOFA) score to identify high-risk patients outside the intensive care unit (ICU).
We sought to compare ...qSOFA with other commonly used early warning scores.
All admitted patients who first met the criteria for suspicion of infection in the emergency department (ED) or hospital wards from November 2008 until January 2016 were included. The qSOFA, Systemic Inflammatory Response Syndrome (SIRS), Modified Early Warning Score (MEWS), and the National Early Warning Score (NEWS) were compared for predicting death and ICU transfer.
Of the 30,677 included patients, 1,649 (5.4%) died and 7,385 (24%) experienced the composite outcome (death or ICU transfer). Sixty percent (n = 18,523) first met the suspicion criteria in the ED. Discrimination for in-hospital mortality was highest for NEWS (area under the curve AUC, 0.77; 95% confidence interval CI, 0.76-0.79), followed by MEWS (AUC, 0.73; 95% CI, 0.71-0.74), qSOFA (AUC, 0.69; 95% CI, 0.67-0.70), and SIRS (AUC, 0.65; 95% CI, 0.63-0.66) (P < 0.01 for all pairwise comparisons). Using the highest non-ICU score of patients, ≥2 SIRS had a sensitivity of 91% and specificity of 13% for the composite outcome compared with 54% and 67% for qSOFA ≥2, 59% and 70% for MEWS ≥5, and 67% and 66% for NEWS ≥8, respectively. Most patients met ≥2 SIRS criteria 17 hours before the combined outcome compared with 5 hours for ≥2 and 17 hours for ≥1 qSOFA criteria.
Commonly used early warning scores are more accurate than the qSOFA score for predicting death and ICU transfer in non-ICU patients. These results suggest that the qSOFA score should not replace general early warning scores when risk-stratifying patients with suspected infection.
Tools that screen inpatients for sepsis use the systemic inflammatory response syndrome (SIRS) criteria and organ dysfunctions, but most studies of these criteria were performed in intensive care ...unit or emergency room populations.
To determine the incidence and prognostic value of SIRS and organ dysfunctions in a multicenter dataset of hospitalized ward patients.
Hospitalized ward patients at five hospitals from November 2008 to January 2013 were included. SIRS and organ system dysfunctions were defined using 2001 International Consensus criteria. Patient characteristics and in-hospital mortality were compared among patients meeting two or more SIRS criteria and by the presence or absence of organ system dysfunction.
A total of 269,951 patients were included in the study, after excluding 48 patients with missing discharge status. Forty-seven percent (n = 125,841) of the included patients met two or more SIRS criteria at least once during their ward stay. On ward admission, 39,105 (14.5%) patients met two or more SIRS criteria, and patients presenting with SIRS had higher in-hospital mortality than those without SIRS (4.3% vs. 1.2%; P < 0.001). Fourteen percent of patients (n = 36,767) had at least one organ dysfunction at ward admission, and those presenting with organ dysfunction had increased mortality compared with those without organ dysfunction (5.3% vs. 1.1%; P < 0.001).
Almost half of patients hospitalized on the wards developed SIRS at least once during their ward stay. Our findings suggest that screening ward patients using SIRS criteria for identifying those with sepsis would be impractical.
Precision cosmology with Type Ia supernovae (SNe Ia) makes use of the fact that SN Ia luminosities depend on their light-curve shapes and colours. Using Supernova Legacy Survey (SNLS) and other data, ...we show that there is an additional dependence on the global characteristics of their host galaxies: events of the same light-curve shape and colour are, on average, 0.08 mag (≃4.0σ) brighter in massive host galaxies (presumably metal-rich) and galaxies with low specific star formation rates (sSFR). These trends do not depend on any assumed cosmological model, and are independent of the SN light-curve width: both fast and slow-declining events show the same trends. SNe Ia in galaxies with a low sSFR also have a smaller slope (‘β’) between their luminosities and colours with ∼2.7σ significance, and a smaller scatter on SN Ia Hubble diagrams (at 95 per cent confidence), though the significance of these effects is dependent on the reddest SNe. SN Ia colours are similar between low-mass and high-mass hosts, leading us to interpret their luminosity differences as an intrinsic property of the SNe and not of some external factor such as dust. If the host stellar mass is interpreted as a metallicity indicator using galaxy mass–metallicity relations, the luminosity trends are in qualitative agreement with theoretical predictions. We show that the average stellar mass, and therefore the average metallicity, of our SN Ia host galaxies decreases with redshift. The SN Ia luminosity differences consequently introduce a systematic error in cosmological analyses, comparable to the current statistical uncertainties on parameters such as w, the equation of state of dark energy. We show that the use of two SN Ia absolute magnitudes, one for events in high-mass (metal-rich) galaxies and the other for events in low-mass (metal-poor) galaxies, adequately corrects for the differences. Cosmological fits incorporating these terms give a significant reduction in χ2 (3.8σ–4.5σ); linear corrections based on host parameters do not perform as well. We conclude that all future SN Ia cosmological analyses should use a correction of this (or similar) form to control demographic shifts in the underlying galaxy population.
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