Observations of a Magellanic Corona Krishnarao, Dhanesh; Fox, Andrew J.; D’Onghia, Elena ...
Nature (London),
09/2022, Letnik:
609, Številka:
7929
Journal Article
Recenzirano
Odprti dostop
Abstract
The Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC) are the closest massive satellite galaxies of the Milky Way. They are probably on their first passage on an infalling ...orbit towards our Galaxy
1
and trace the continuing dynamics of the Local Group
2
. Recent measurements of a high mass for the LMC (
M
halo
≈ 10
11.1–11.4
M
⊙
)
3–6
imply that the LMC should host a Magellanic Corona: a collisionally ionized, warm-hot gaseous halo at the virial temperature (10
5.3–5.5
K) initially extending out to the virial radius (100–130 kiloparsecs (kpc)). Such a corona would have shaped the formation of the Magellanic Stream
7
, a tidal gas structure extending over 200° across the sky
2,8,9
that is bringing in metal-poor gas to the Milky Way
10
. Here we show evidence for this Magellanic Corona with a potential direct detection in highly ionized oxygen (O
+5
) and indirectly by means of triply ionized carbon and silicon, seen in ultraviolet (UV) absorption towards background quasars. We find that the Magellanic Corona is part of a pervasive multiphase Magellanic circumgalactic medium (CGM) seen in many ionization states with a declining projected radial profile out to at least 35 kpc from the LMC and a total ionized CGM mass of log
10
(
M
H II,CGM
/
M
⊙
) ≈ 9.1 ± 0.2. The evidence for the Magellanic Corona is a crucial step forward in characterizing the Magellanic group and its nested evolution with the Local Group.
Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair ...(HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.
Friends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.
This publication provides findings from the group's discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.
Overall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.
The incidence and prevalence of granulomatosis with polyangiitis (GPA) in the US is not well characterized. Owing to its rarity, outcomes data in pediatric-onset GPA are also lacking. The aims of ...this study were to describe the epidemiology of GPA and outcomes in GPA patients in the US, and to compare outcomes between pediatric and working-age adult patients.
A retrospective cohort study using the 2006-2014 Truven Health Analytics MarketScan Commercial Claims and Encounters Database was conducted. The incidence and prevalence rates of pediatric and adult GPA (age <65 years) were calculated. Outcomes among the 2 age groups were analyzed.
A total of 5,562 cases of GPA were identified, of which 214 (3.8%) were pediatric onset and 5,348 (96.2%) were adult onset. The incidence rate of pediatric-onset GPA was 1.8 cases per 1 million person-years, compared to 12.8 cases per 1 million person-years in working-age adults. There was a slight female preponderance in both groups (63% and 53% among pediatric and adult GPA patients, respectively). Rates of hospitalization and severe infections were high in both children and working-age adults, but children had more frequent hospitalizations (rate ratio RR 1.3 95% confidence interval (95% CI) 1.1-1.4) and 2-3-times higher rates of leukopenia (RR 2.6 95% CI 1.5-4.3), neutropenia (RR 2.2 95% CI 1.2-4.0), and hypogammaglobulinemia (RR 3.7 95% CI 2.0-6.4). Time-to-event analyses showed no differences in the time to hospitalization, severe infection, major relapse, or end-stage renal disease.
This study represents the largest cohort of GPA reported to date. Pediatric GPA patients experienced more frequent hospitalizations and were more vulnerable to hematologic complications than non-elderly adult patients.
Spinal muscular atrophy (SMA), caused by loss of the SMN1 gene, is a leading cause of early childhood death. Due to the near identical sequences of SMN1 and SMN2, analysis of this region is ...challenging. Population-wide SMA screening to quantify the SMN1 copy number (CN) is recommended by the American College of Medical Genetics and Genomics.
We developed a method that accurately identifies the CN of SMN1 and SMN2 using genome sequencing (GS) data by analyzing read depth and eight informative reference genome differences between SMN1/2.
We characterized SMN1/2 in 12,747 genomes, identified 1568 samples with SMN1 gains or losses and 6615 samples with SMN2 gains or losses, and calculated a pan-ethnic carrier frequency of 2%, consistent with previous studies. Additionally, 99.8% of our SMN1 and 99.7% of SMN2 CN calls agreed with orthogonal methods, with a recall of 100% for SMA and 97.8% for carriers, and a precision of 100% for both SMA and carriers.
This SMN copy-number caller can be used to identify both carrier and affected status of SMA, enabling SMA testing to be offered as a comprehensive test in neonatal care and an accurate carrier screening tool in GS sequencing projects.
To better understand the impact of the Deepwater Horizon (DWH) incident on commercially and ecologically important pelagic fish species, a mahi-mahi spawning program was developed to assess the ...effect of embryonic exposure to DWH crude oil with particular emphasis on the effects of weathering and dispersant on the magnitude of toxicity. Acute lethality (96h LC50) ranged from 45.8 (28.4–63.1) μgl−1 ΣPAH for wellhead (source) oil to 8.8 (7.4–10.3) μgl−1 ΣPAH for samples collected from the surface slick, reinforcing previous work that weathered oil is more toxic on a ΣPAH basis. Differences in toxicity appear related to the amount of dissolved 3 ringed PAHs. The dispersant Corexit 9500 did not influence acute lethality of oil preparations. Embryonic oil exposure resulted in cardiotoxicity after 48h, as evident from pericardial edema and reduced atrial contractility. Whereas pericardial edema appeared to correlate well with acute lethality at 96h, atrial contractility did not. However, sub-lethal cardiotoxicity may impact long-term performance and survival. Dispersant did not affect the occurrence of pericardial edema; however, there was an apparent reduction in atrial contractility at 48h of exposure. Pericardial edema at 48h and lethality at 96h were equally sensitive endpoints in mahi-mahi.
Display omitted
•Weathering of crude oil increases the toxicity of water accommodated fractions.•Dispersant does not change lethal or sub-lethal oil toxicity in larval fish.•Pelagic larvae are sensitive to weathered oil at low μg/l ΣPAH concentrations.•There is a close relationship between survival and cardiotoxicity between oil types.
Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with ...suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts.
The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the
test, χ
statistics, and logistic regression analyses.
A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts.
In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.
Abstract
Background
Acceptability is recognised as a key concept in the development of health interventions, but there has been a lack of consensus about how acceptability should be conceptualised. ...The theoretical framework of acceptability (TFA) provides a potential tool for understanding acceptability. It has been proposed that acceptability measured before use of an intervention (anticipated acceptability) may differ from measures taken during and after use (experienced acceptability), but thus far this distinction has not been tested for a specific intervention. This paper 1) directly compares ratings of anticipated and experienced acceptability of a text message-based intervention, 2) explores the applicability of the TFA in a technology-based intervention, and 3) uses these findings to inform suggestions for measuring acceptability over the lifespan of technology-based health interventions.
Methods
Data were obtained from a quantitative online survey assessing anticipated acceptability of the proposed text messages (
n
= 59) and a 12-week proof-of-concept mixed methods study assessing experienced acceptability while receiving the text messages (
n
= 48). Both quantitative ratings by return text message, and qualitative data from participant interviews were collected during the proof-of-concept study.
Results
The quantitative analysis showed anticipated and experienced acceptability were significantly positively correlated (r
s
> .4). The qualitative analysis identified four of the seven constructs of the TFA as themes (burden, intervention coherence, affective attitude and perceived effectiveness). An additional two themes were identified as having an important impact on the TFA constructs (perceptions of appropriateness and participants’ role). Three suggestions are given related to the importance of appropriateness, what may affect ratings of acceptability and what to consider when measuring acceptability.
Conclusions
The high correlation between anticipated and experienced acceptability was a surprising finding and could indicate that, in some cases, acceptability of an intervention can be gauged adequately from an anticipated acceptability study, prior to an expensive pilot or feasibility study. Directly exploring perceptions of appropriateness and understanding whether the acceptability described by participants is related to the intervention or the research - and is for themselves or others - is important in interpreting the results and using them to further develop interventions and predict future use.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current interventions to support medication adherence in people with type 2 diabetes are generally resource-intensive and ineffective. Brief messages, such as those delivered via short message ...service (SMS) systems, are increasingly used in digital health interventions to support adherence because they can be delivered on a wide scale and at low cost. The content of SMS text messages is a crucial intervention feature for promoting behavior change, but it is often unclear what the rationale is for chosen wording or any underlying mechanisms targeted for behavioral change. There is little guidance for developing and optimizing brief message content for use in mobile device-delivered interventions.
This review aimed to (1) identify theoretical constructs (ie, the targets that interventions aim to change) and behavioral strategies (ie, features of intervention content) found to be associated with medication adherence in patients with type 2 diabetes and (2) map these onto a standard taxonomy for behavior change techniques (BCTs, that is, active ingredients of interventions used to promote behavioral change, to produce an evidence-based set of approaches that have shown promise of improving adherence in previous studies and which could be further tested in digital health interventions.
A rapid systematic review of existing relevant systematic reviews was conducted. MEDLINE and PsycINFO databases were searched from inception to April 10, 2017. Inclusion criteria were (1) systematic reviews of quantitative data if the studies reviewed identified predictors of or correlates with medication adherence or evaluated medication adherence-enhancing interventions and included adult participants taking medication to manage a chronic physical health condition, and (2) systematic reviews of qualitative studies of experiences of medication adherence for adult participants with type 2 diabetes. Data were extracted on review characteristics and BCTs, theoretical constructs, or behavioral strategies associated with improved adherence. Constructs and strategies were mapped onto the BCT version 1 taxonomy.
A total of 1701 references were identified; 25 systematic reviews (19 quantitative reviews, 3 qualitative reviews, and 3 mixed-method reviews) were included. Moreover, 20 theoretical constructs (eg, self-efficacy) and 19 behavioral strategies (eg, habit analysis) were identified in the included reviews. In total, 46 BCTs were identified as being related to medication adherence in type 2 diabetes (eg, habit formation, prompts or cues, and information about health consequences).
We identified 46 promising BCTs related to medication adherence in type 2 diabetes on which the content of brief messages delivered through mobile devices to improve adherence could be based. By using explicit systematic review methods and linking our findings to a standardized taxonomy of BCTs, we have described a novel approach for the development of digital message content. Future brief message interventions that aim to support medication adherence could incorporate the identified BCTs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Multidisciplinary transitional care services reduce readmissions for high-risk patients, but it is unclear if health system costs to offer these intensive services are offset by avoidance ...of higher downstream expenditures.
Objective
To evaluate net costs for a health system offering transitional care services
Design
One-year pragmatic, randomized trial
Participants
Adults aged ≥ 18 without a usual source of follow-up care at the time of hospital discharge were enrolled through a high-volume, urban academic medical center in Chicago, IL, USA, from September 2015 through February 2016.
Interventions
Eligible patients were silently randomized before discharge by an automated electronic health record algorithm allocating them in a 1:3 ratio to receive routine coordination of post-discharge care (RC) versus being offered intensive, multidisciplinary transitional care (TC) services.
Main Measurements
Health system costs were collected from facility administrative systems and transformed to standardized costs using Medicare reference files. Multivariable generalized linear models estimated proportional differences in net costs over one year.
Key Results
Study patients (489 TC; 164 RC) had a mean age of 44 years; 34% were uninsured, 55% had public insurance, and 49% self-identified as Black or Latinx. Over 90 days, cost differences between groups were not statistically significant. Over 180 days, the TC group had 41% lower ED/observation costs (adjusted cost ratio aCR, 0.59; 95% CI, 0.36–0.97), 50% lower inpatient costs (aCR, 0.50; 95% CI, 0.27–0.95), and 41% lower total healthcare costs (aCR, 0.59; 95% CI, 0.36–0.99) than the RC group. Over 365 days, total cost differences remained of similar magnitude but no longer were statistically significant.
Conclusions
Offering TC services for vulnerable adults at discharge reduced net health system expenditures over 180 days. The promising economic case for multidisciplinary transitional care interventions warrants further research.
Trial Registration
National Clinical Trials Registry (NCT03066492)
Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not ...been reported, but would facilitate diagnostic test development. To identify minimal transcript signatures, we applied a transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were further investigated using reverse transcriptase (RT)-digital PCR (dPCR). A four-transcript signature (
, and
) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI
82.2-100%). A three-transcript signature (
) differentiated TB from LTBI (AUC 97.3%, CI
: 93.3-100%), regardless of HIV. These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.
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