We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Patients with hematological malignancies are at high risk of infections due to both the disease and the associated treatments. The use of immunoglobulin (Ig) to prevent infections is increasing in this population, but its cost effectiveness is unknown. This trial-based economic evaluation aimed to compare the cost effectiveness of prophylactic Ig with prophylactic antibiotics in patients with hematological malignancies.
Methods
The economic evaluation used individual patient data from the RATIONAL feasibility trial, which randomly assigned 63 adults with chronic lymphocytic leukemia, multiple myeloma, or lymphoma to prophylactic Ig or prophylactic antibiotics. The following two analyses were conducted to estimate the cost effectiveness of the two treatments over the 12-month trial period from the perspective of the Australian health system:
(i) a cost-utility analysis (CUA) to assess the incremental cost per quality-adjusted life-year (QALY) gained using data collected with the EuroQol 5D-5L questionnaire; and
(ii) a cost-effectiveness analysis (CEA) to assess the incremental cost per serious infection prevented (grade ≥3) and per infection prevented (any grade).
Results
The total cost per patient was significantly higher in the Ig arm than in the antibiotic arm (difference AUD29,140 [USD19,000]). There were non-significant differences in health outcomes between the treatment arms: patients treated with Ig had fewer QALYs (difference −0.072) and serious infections (difference −0.26) than those given antibiotics, but more overall infections (difference 0.76). The incremental cost-effectiveness from the CUA indicated that Ig was more costly than antibiotics and associated with fewer QALYs. In the CEA, Ig costed an additional AUD111,262 (USD73,000) per serious infection prevented, but it was more costly than antibiotics and associated with more infections when all infections were included.
Conclusions
These results indicate that, on average, Ig prophylactic treatment may not be cost effective compared with prophylactic antibiotics for the group of patients with hematological malignancies recruited to the RATIONAL feasibility trial. Further research is needed to confirm these findings in a larger population and over the longer term.
The bright radio source, GLEAM J091734$-$001243 (hereafter GLEAM J0917$-$0012), was previously selected as a candidate ultra-high redshift ($z \gt 5$) radio galaxy due to its compact radio size and faint magnitude ($K(\mathrm{AB})=22.7$). Its redshift was not conclusively determined from follow-up millimetre and near-infrared spectroscopy. Here we present new HST WFC3 G141 grism observations which reveal several emission lines including [NeIII]$\lambda$3867, [NeV]$\lambda$3426 and an extended ($\approx 4.8\,$kpc), [OII]$\lambda$3727 line which confirm a redshift of $3.004\pm0.001$. The extended component of the [OII]$\lambda$3727 line is co-spatial with one of two components seen at 2.276 GHz in high resolution ($60\times 20\,$mas) Long Baseline Array data, reminiscent of the alignments seen in local compact radio galaxies. The BEAGLE stellar mass ($\approx 2\times 10^{11}\,\textit{M}_\odot$) and radio luminosity ($L_{\mathrm{500MHz}}\approx 10^{28}\,$W Hz$^{-1}$) put GLEAM J0917$-$0012 within the distribution of the brightest high-redshift radio galaxies at similar redshifts. However, it is more compact than all of them. Modelling of the radio jet demonstrates that this is a young, $\approx 50\,$kyr old, but powerful, $\approx 10^{39}\,$W, compact steep spectrum radio source. The weak constraint on the active galactic nucleus bolometric luminosity from the [NeV]$\lambda$3426 line combined with the modelled jet power tentatively implies a large black hole mass, $\ge 10^9\,\textit{M}_\odot$, and a low, advection-dominated accretion rate, i.e. an Eddington ratio $\le 0.03$. The [NeV]$\lambda$3426/[NeIII]$\lambda$3867 vs [OII]$\lambda$3727/[NeIII]$\lambda$3867 line ratios are most easily explained by radiative shock models with precursor photoionisation. Hence, we infer that the line emission is directly caused by the shocks from the jet and that this radio source is one of the youngest and most powerful known at cosmic noon. We speculate that the star-formation in GLEAM J0917$-$0012 could be on its way to becoming quenched by the jet.
The nature of interstratification in mixed-layer illite-montmorillonites has been investigated by comparison of diffraction patterns of ethylene glycol and ethylene glycol monoethyl ether treated samples with calculated one-dimensional diffraction profiles. The calculated profiles take into account the effects of particle size distribution, chemical composition, and convolution factors as well as proportions of layers and interstratification type. On the basis of detailed matching of diffraction patterns of monomineralic illite-montmorillonites of known chemical composition it is concluded that there are three types of interstratification: (1) random, (2) allevardite-like ordering, and (3) superlattice units consisting of three illite and one montmorillonite layers (IMII). By comparison of suites of calculated profiles with the diffraction patterns of many samples of illite-montmorillonites it is concluded that virtually all illite-montmorillonites with expandabilities from about 40 to 100 per cent are randomly interstratified (allevardite being exceptional); at >40 per cent montmorillonite layers they almost always have ordered interstratification. Allevardite-like ordering predominates in illitemontmorillonites which have ordered interstratification, with the IMII superlattice varieties confined to samples with about 10 per cent montmorillonite layers.
This study identified 26 late invasive primary surgical site infection (IP-SSI) within 4–12 months of transplantation among 2073 SOT recipients at Duke University Hospital over the period 2015–2019. Thoracic organ transplants accounted for 25 late IP-SSI. Surveillance for late IP-SSI should be maintained for at least one year following transplant.
OBJECTIVES/GOALS: Prematurity and perinatal brain injury are known risk factors for strabismus. In this study, we sought to understand the link between neonatal neuroimaging measures in very preterm infants and the emergence of strabismus later in life. Study findings may inform if neonatal brain MRI could serve as a prognostic tool for this visual disorder. METHODS/STUDY POPULATION: This study draws from a longitudinal cohort of very preterm infants (VPT, < 30 weeks gestation, range 23 – 29 weeks) who underwent an MRI scan at 36 to 43 weeks postmenstrual age (PMA). Anatomic and diffusion MRI data were collected for each child . A subset of thirty-three patients in this cohort had records of an eye exam, which were reviewed for a history of strabismus. Patients with MRI scans demonstrating cystic periventricular leukomalacia or grade III/IV intraventricular hemorrhage were classified as having brain injury. Clinical variables with a known association to strabismus or diffusion metrics were included in a multivariable logistic regression model. Diffusion tractography metrics were screened for association with strabismus on univariable analysis prior to inclusion in the regression model. RESULTS/ANTICIPATED RESULTS: A total of 17/33 (51.5%) patients developed strabismus. A logistic regression model including gestational age, PMA at MRI, retinopathy of prematurity (ROP) stage, brain injury, and fractional anisotropy of the right optic radiation was significant at the .001 level according to the chi-square statistic. The model predicted 88% of responses correctly. Each decrease of 0.01 in the fractional anisotropy of the right optic radiation increased the odds of strabismus by a factor of 1.5 (95% CI 1.03 – 2.06; p = .03). Patients with brain injury had 15.8 times higher odds of strabismus (95% CI 1.1 – 216.5; p = .04). Gestational age (OR 1.7; 95% CI 0.9 – 3.3; p = .1) and stage of ROP (OR 0.6; 95% CI 0.2 – 2.0; p = .4) were not significant predictors of strabismus in the multivariable model. DISCUSSION/SIGNIFICANCE: Our findings suggest that strabismus in VPT patients may be related to specific changes in brain structure in the neonatal period. The identified association between neonatal optic radiation microstructure and strabismus supports the possibility of using brain MRI in very preterm infants to prognosticate visual and ocular morbidity.
Compassionate, non-judgemental abortion care should be provided to women seeking to end a pregnancy at the earliest gestation as possible and as late as necessary. Laws that prohibit abortion do not prevent abortion, but merely result in more unsafe abortions [1]. The legal requirements to access abortion vary significantly across Europe, and it is important for clinicians to be aware of their own country’s regulations but also those of their close neighbours, as it is common for women who live in areas of greater restriction to travel to nearby countries with less restrictive legislation.
Abortion is the most common gynaecological procedure worldwide and on average 56 million abortions are performed globally each year. One third of women will experience an induced abortion in their lifetime and most of them will have a single abortion [1]. When abortion is performed safely in a legal setting the complication rate is low and long-term morbidity and mortality are virtually non-existent [2] and 14 times lower than for childbirth [3]. However, less safe and least safe abortions are responsible for 31,000 maternal deaths and 7 million hospital admissions for complications globally each year [1].
Medical abortion is the use of medications, rather than surgical means to induce an abortion. The World Health Organization (WHO) recommends the use of a combination of mifepristone (a progesterone-receptor antagonist) followed by misoprostol (a synthetic prostaglandin) [1].
The International VLBI Service for Geodesy and Astrometry (IVS) regularly provides high-quality data to produce Earth Orientation Parameters (EOP), and for the maintenance and realisation of the International Terrestrial and Celestial Reference Frames, ITRF and ICRF. The first iteration of the celestial reference frame (CRF) at radio wavelengths, the ICRF1, was adopted by the International Astronomical Union (IAU) in 1997 to replace the FK5 optical frame. Soon after, the IVS began official operations and in 2009 there was a significant increase in data sufficient to warrant a second iteration of the CRF, ICRF2. The most recent ICRF3, was adopted by the IAU in 2018. However, due to the geographic distribution of observing stations being concentrated in the Northern hemisphere, CRFs are generally weaker in the South due to there being fewer Southern Hemisphere observations. To increase the Southern Hemisphere observations, and the density, precision of the sources, a series of deep South observing sessions was initiated in 1995. This initiative in 2004 became the IVS Celestial Reference Frame Deep South (IVS-CRDS) observing programme. This paper covers the evolution of the CRDS observing programme for the period 1995–2021, details the data products and results, and concludes with a summary of upcoming improvements to this ongoing project.
In 1922, the League of Nations inscribed the goal of establishing a settler colony in Palestine for the Jewish people—in denial of the national self-determination of the Indigenous Arab population—in public international law. The Palestine Mandate juridically erased the national status of the Palestinian people by: (1) framing the Arabs as incapable of self-rule; (2) heightening the significance of establishing a Jewish national home; and (3) distinguishing Palestine from the other Class A mandates for possessing religious significance that exceeded the interests of any single national group. A century later, the still-unresolved “question” of Palestine remains central to struggles for anti-racism and anti-colonialism in international law. This essay revisits two flashpoints in the tangled history of Palestine and international law, where questions of race and racism have been central: first, ongoing debates over the regime and crime of apartheid; and second, the now-repudiated UN General Assembly Resolution 3379, recognizing Zionism as a form of racism and racial discrimination. Both stories demonstrate the importance of understanding race and colonialism as conjoined concepts, neither of which can be properly understood in isolation from the other.
Partial agonists of dopamine receptors are used in combination with full antagonists in treating psychosis, either to mitigate side-effects or in the hope of increasing effectiveness. We examine how combinations may affect the occupancy of D2/D3 dopamine receptors and explore how these can explain the outcomes in the light of the dopamine hypothesis of psychosis. The combinations considered here are from published studies combining aripiprazole with amisulpride, with risperidone in people with hyperprolactinaemia and with olanzapine to mitigate weight gain. We discuss possible worsening of symptoms by the addition of a partial agonist or switching. We also examine the potentially adverse interaction with a full antagonist such as haloperidol given during a subsequent relapse to control severe agitation.
It is now over thirty years since epidemiological studies revealed a relationship between low birth weight and subsequent risk of developing traditionally adult-onset diseases, such as type 2 diabetes, cardiovascular and renal disease. Initial focus was directed towards the importance of fetal undernutrition. However, it is now recognized that a range of other in utero adverse exposures including chronic fetal hypoxia, maternal over-nutrition and maternal stress can also lead to increased risk of cardio-metabolic and renal diseases in later life. Animal models, including those using non-human primates, sheep and rodents have been critical in demonstrating causality of relationships and helped to define underlying mechanisms, such as epigenetic programming of gene expression and oxidative stress. As the field moves forward in the coming years, these mechanistic studies will help to identify rational intervention strategies to reduce the developmental programming of cardiometabolic and renal dysfunction in suboptimal pregnancy.
Cardiac intensivists frequently assess patient readiness to wean off mechanical ventilation with an extubation readiness trial despite it being no more effective than clinician judgement alone. We evaluated the utility of high-frequency physiologic data and machine learning for improving the prediction of extubation failure in children with cardiovascular disease.
Methods:
This was a retrospective analysis of clinical registry data and streamed physiologic extubation readiness trial data from one paediatric cardiac ICU (12/2016-3/2018). We analysed patients’ final extubation readiness trial. Machine learning methods (classification and regression tree, Boosting, Random Forest) were performed using clinical/demographic data, physiologic data, and both datasets. Extubation failure was defined as reintubation within 48 hrs. Classifier performance was assessed on prediction accuracy and area under the receiver operating characteristic curve.
Results:
Of 178 episodes, 11.2% (N = 20) failed extubation. Using clinical/demographic data, our machine learning methods identified variables such as age, weight, height, and ventilation duration as being important in predicting extubation failure. Best classifier performance with this data was Boosting (prediction accuracy: 0.88; area under the receiver operating characteristic curve: 0.74). Using physiologic data, our machine learning methods found oxygen saturation extremes and descriptors of dynamic compliance, central venous pressure, and heart/respiratory rate to be of importance. The best classifier in this setting was Random Forest (prediction accuracy: 0.89; area under the receiver operating characteristic curve: 0.75). Combining both datasets produced classifiers highlighting the importance of physiologic variables in determining extubation failure, though predictive performance was not improved.
Conclusion:
Physiologic variables not routinely scrutinised during extubation readiness trials were identified as potential extubation failure predictors. Larger analyses are necessary to investigate whether these markers can improve clinical decision-making.
Unintended pregnancy is common. It is estimated that one in three pregnancies end in abortion. Management of unintended pregnancy, in the form of surgical and medical abortion, is an essential part of reproductive healthcare and fundamental for training in obstetrics and gynaecology. Comprehensive abortion care includes provision of accurate information on methods of abortion, provision of abortion and post-abortion care.
This chapter will provide background on the prevalence of abortion, pre-abortion assessment, methods of abortion, post-abortion contraception and management of abortion-related complications.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
Incentivizing the development of interdisciplinary scientific teams to address significant societal challenges usually takes the form of pilot funding. However, while pilot funding is likely necessary, it is not sufficient for successful collaborations. Interdisciplinary collaborations are enhanced when team members acquire competencies that support team success.
Methods:
We evaluated the impact of a multifaceted team development intervention that included an eight-session workshop spanning two half-days. The workshop employed multiple methods for team development, including lectures on empirically supported best practices, skills-based modules, role plays, hands-on planning sessions, and social interaction within and across teams. We evaluated the impact of the intervention by (1) asking participants to assess each of the workshop sessions and (2) by completing a pre/postquestionnaire that included variables such as readiness to collaborate, goal clarity, process clarity, role ambiguity, and behavioral trust.
Results:
The content of the team development intervention was very well received, particularly the workshop session focused on psychological safety. Comparison of survey scores before and after the team development intervention indicated that scores on readiness to collaborate and behavioral trust were significantly higher among participants who attended the workshop. Goal clarity, process clarity, and role ambiguity did not differ among those who attended versus those who did not.
Conclusions:
Multicomponent team development interventions that focus on key competencies required for interdisciplinary teams can support attitudes and cognitions that the literature on the science of team science indicate are predictive of success. We offer recommendations for the design of future interventions.
The coronavirus disease 2019 (COVID-19) created major disruptions at academic centers and healthcare systems globally. Clinical and Translational Science Awards (CTSA) fund hubs supported by the National Center for Advancing Translational Sciences provideinfrastructure and leadership for clinical and translational research at manysuch institutions.
Methods:
We surveyed CTSA hubs and received responses from 94% of them regarding the impact of the pandemic and the processes employed for the protection of research personnel and participants with respect to the conduct of research, specifically for studies unrelated to COVID-19.
Results:
In this report, we describe the results of the survey findings in the context of the current understanding of disease transmission and mitigation techniques.
Conclusions:
We reflect on common practices and provide recommendations regarding lessons learned that will be relevant to future pandemics, particularly with regards to staging the cessation and resumption of research activities with an aim to keep the workforce, research participants, and our communities safe in future pandemics.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
$\sim$
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
$+41^\circ$
made over a 288-MHz band centred at 887.5 MHz.
The European Union's external border regime is a manifestation of continuing imperialism. It reinforces particular imaginaries of Europe's wealth as somehow innate (rather than plundered and extorted) and of Europeanness itself as whiteness—euphemistically packaged as a “European Way of Life” to be protected. This exposes international law's structural limitations—if not designs—as bound up with racial borders in the global context. In the wake of COVID-19 and with a climate apocalypse already underway, these realities need to be urgently ruptured and reimagined.