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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.
The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.
The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
Here we present stringent low-frequency (185 MHz) limits on coherent radio emission associated with a short-duration gamma-ray burst (SGRB). Our observations of the short gamma-ray burst (GRB) 180805A were taken with the upgraded Murchison Widefield Array (MWA) rapid-response system, which triggered within 20s of receiving the transient alert from the Swift Burst Alert Telescope, corresponding to 83.7 s post-burst. The SGRB was observed for a total of 30 min, resulting in a
persistent flux density upper limit of 40.2 mJy beam–1. Transient searches were conducted at the Swift position of this GRB on 0.5 s, 5 s, 30 s and 2 min timescales, resulting in
limits of 570–1 830, 270–630, 200–420, and 100–200 mJy beam–1, respectively. We also performed a dedispersion search for prompt signals at the position of the SGRB with a temporal and spectral resolution of 0.5 s and 1.28 MHz, respectively, resulting in a
fluence upper-limit range from 570 Jy ms at DM
pc cm–3 (
) to 1 750 Jy ms at DM
pc cm–3 (
, corresponding to the known redshift range of SGRBs. We compare the fluence prompt emission limit and the persistent upper limit to SGRB coherent emission models assuming the merger resulted in a stable magnetar remnant. Our observations were not sensitive enough to detect prompt emission associated with the alignment of magnetic fields of a binary neutron star just prior to the merger, from the interaction between the relativistic jet and the interstellar medium (ISM) or persistent pulsar-like emission from the spin-down of the magnetar. However, in the case of a more powerful SGRB (a gamma-ray fluence an order of magnitude higher than GRB 180805A and/or a brighter X-ray counterpart), our MWA observations may be sensitive enough to detect coherent radio emission from the jet-ISM interaction and/or the magnetar remnant. Finally, we demonstrate that of all current low- frequency radio telescopes, only the MWA has the sensitivity and response times capable of probing prompt emission models associated with the initial SGRB merger event.
Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
Chinese privet (Ligustrum sinense Lour.) is a deciduous to evergreen shrub with an expansive nonnative global range. Control costs are often high, so land managers must carefully consider whether the plant’s potential negative effects warrant active management. To help facilitate this decision-making process, we reviewed and synthesized the literature on the potential ecological effects of L. sinense invasion. We also identified research gaps in need of further study. We found ample evidence of negative relationships between L. sinense invasion and native plant communities. While observational studies are not able to confirm whether L. sinense is driving these relationships, experimental evidence suggests that there is a cause–effect relationship. Of particular concern is the possibility that L. sinense could suppress forest regeneration and cause areas to transition from forest to L. sinense–dominated shrublands. Although this outcome would obviously impact a wide variety of wildlife species, empirical evidence of negative effects of L. sinense on wildlife are limited, and some species may actually benefit from the additional cover and foraging opportunities that L. sinense can provide. Further research on the potential effects of L. sinense invasion on large-scale forest structure and wildlife populations is needed. In areas where L. sinense invasion is a concern, evidence suggests early detection and management can mitigate control costs.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Multispectral imaging – the acquisition of spatially contiguous imaging data in a modest number (~3–16) of spectral bandpasses – has proven to be a powerful technique for augmenting panchromatic imaging observations on Mars focused on geologic and/or atmospheric context. Specifically, multispectral imaging using modern digital CCD photodetectors and narrowband filters in the 400–1100 nm wavelength region on the Mars Pathfinder, Mars Exploration Rover, Phoenix, and Mars Science Laboratory missions has provided new information on the composition and mineralogy of fine-grained regolith components (dust, soils, sand, spherules, coatings), rocky surface regions (cobbles, pebbles, boulders, outcrops, and fracture-filling veins), meteorites, and airborne dust and other aerosols. Here we review recent scientific results from Mars surface-based multispectral imaging investigations, including the ways that these observations have been used in concert with other kinds of measurements to enhance the overall scientific return from Mars surface missions.
Starburst galaxies are often found to be the result of galaxy mergers. As a result, galaxy mergers are often believed to lie above the galaxy main sequence: the tight correlation between stellar mass and star formation rate. Here, we aim to test this claim.
Deep learning techniques are applied to images from the Sloan Digital Sky Survey to provide visual-like classifications for over 340 000 objects between redshifts of 0.005 and 0.1. The aim of this classification is to split the galaxy population into merger and non-merger systems and we are currently achieving an accuracy of 92.5%. Stellar masses and star formation rates are also estimated using panchromatic data for the entire galaxy population. With these preliminary data, the mergers are placed onto the full galaxy main sequence, where we find that merging systems lie across the entire star formation rate - stellar mass plane.
To sustainably improve cleaning of high-touch surfaces (HTSs) in acute-care hospitals using a multimodal approach to education, reduction of barriers to cleaning, and culture change for environmental services workers.
The study was conducted in 2 academic acute-care hospitals, 2 community hospitals, and an academic pediatric and women’s hospital.
Frontline environmental services workers.
A 5-module educational program, using principles of adult learning theory, was developed and presented to environmental services workers. Audience response system (ARS), videos, demonstrations, role playing, and graphics were used to illustrate concepts of and the rationale for infection prevention strategies. Topics included hand hygiene, isolation precautions, personal protective equipment (PPE), cleaning protocols, and strategies to overcome barriers. Program evaluation included ARS questions, written evaluations, and objective assessments of occupied patient room cleaning. Changes in hospital-onset C. difficile infection (CDI) and methicillin-resistant S. aureus (MRSA) bacteremia were evaluated.
On average, 357 environmental service workers participated in each module. Most (93%) rated the presentations as ‘excellent’ or ‘very good’ and agreed that they were useful (95%), reported that they were more comfortable donning/doffing PPE (91%) and performing hand hygiene (96%) and better understood the importance of disinfecting HTSs (96%) after the program. The frequency of cleaning individual HTSs in occupied rooms increased from 26% to 62% (P < .001) following the intervention. Improvement was sustained 1-year post intervention (P < .001). A significant decrease in CDI was associated with the program.
A novel program that addressed environmental services workers’ knowledge gaps, challenges, and barriers was well received and appeared to result in learning, behavior change, and sustained improvements in cleaning.
The prevalence of mental disorders among Black, Latino, and Asian adults is lower than among Whites. Factors that explain these differences are largely unknown. We examined whether racial/ethnic differences in exposure to traumatic events (TEs) or vulnerability to trauma-related psychopathology explained the lower rates of psychopathology among racial/ethnic minorities.
We estimated the prevalence of TE exposure and associations with onset of DSM-IV depression, anxiety and substance disorders and with lifetime post-traumatic stress disorder (PTSD) in the Collaborative Psychiatric Epidemiology Surveys, a national sample (N = 13 775) with substantial proportions of Black (35.9%), Latino (18.9%), and Asian Americans (14.9%).
TE exposure varied across racial/ethnic groups. Asians were most likely to experience organized violence – particularly being a refugee – but had the lowest exposure to all other TEs. Blacks had the greatest exposure to participation in organized violence, sexual violence, and other TEs, Latinos had the highest exposure to physical violence, and Whites were most likely to experience accidents/injuries. Racial/ethnic minorities had lower odds ratios of depression, anxiety, and substance disorder onset relative to Whites. Neither variation in TE exposure nor vulnerability to psychopathology following TEs across racial/ethnic groups explained these differences. Vulnerability to PTSD did vary across groups, however, such that Asians were less likely and Blacks more likely to develop PTSD following TEs than Whites.
Lower prevalence of mental disorders among racial/ethnic minorities does not appear to reflect reduced vulnerability to TEs, with the exception of PTSD among Asians. This highlights the importance of investigating other potential mechanisms underlying racial/ethnic differences in psychopathology.
Paleoecological data from the Quaternary Period (2.6 million years ago to present) provides an opportunity for educational outreach for the earth and biological sciences. Paleoecology data repositories serve as technical hubs and focal points within their disciplinary communities and so are uniquely situated to help produce teaching modules and engagement resources. The Neotoma Paleoecology Database provides support to educators from primary schools to graduate students. In collaboration with pedagogical experts, the Neotoma Paleoecology Database team has developed teaching modules and model workflows. Early education is centered on discovery; higher-level educational tools focus on illustrating best practices for technical tasks. Collaborations among pedagogic experts, technical experts and data stewards, centered around data resources such as Neotoma, provide an important role within research communities, and an important service to society, supporting best practices, translating current research advances to interested audiences, and communicating the importance of individual research disciplines.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.
The Rockefeller Clinical Scholars (KL2) program began in 1976 and transitioned into a 3-year Master’s degree program in 2006 when Rockefeller joined the National Institute of Health Clinical and Translational Science Award program. The program consists of ∼15 trainees supported by the Clinical and Translational Science Award KL2 award and University funds. It is designed to provide an optimal environment for junior translational investigators to develop team science and leadership skills by designing and performing a human subjects protocol under the supervision of a distinguished senior investigator mentor and a team of content expert educators. This is complemented by a tutorial focused on important translational skills.
Since 2006, 40 Clinical Scholars have graduated from the programs and gone on to careers in academia (72%), government service (5%), industry (15%), and private medical practice (3%); 2 (5%) remain in training programs; 39/40 remain in translational research careers with 23 National Institute of Health awards totaling $23 million, foundation and philanthropic support of $20.3 million, and foreign government and foundation support of $6 million. They have made wide ranging scientific discoveries and have endeavored to translate those discoveries into improved human health.
The Rockefeller Clinical Scholars (KL2) program provides one model for translational science training.
We deposited TaWSi amorphous metal thin films to determine how composition affects film crystallization and oxidation at high temperatures. Films were deposited by magnetron sputtering from targets of nominal compositions Ta : W : Si = 40 : 40 : 20, 30 : 50 : 20, and 30 : 30 : 40, and studied by electron probe microanalysis, electron microscopy, electrical methods, x-ray diffraction, x-ray photoelectron spectroscopy, and atomic-force microscopy. All films remained amorphous to 800 °C or higher temperatures. Films prepared from the target composition 30 : 30 : 40 yielded the film composition Ta41.7W38.4Si19.9, which retained its film integrity and amorphous structure to 1100 °C, even after annealing in air.