Please cite this paper as: Moss J, Cooper K, Khaund A, Murray L, Murray G, Wu O, Craig L, Lumsden M. Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients ...with symptomatic uterine fibroids (REST trial): 5‐year results. BJOG 2011;118:936–944.
Objective To compare the long‐term results of uterine artery embolisation (UAE) with surgery for women with symptomatic uterine fibroids.
Design Pragmatic, open, multicentre, randomised trial.
Setting Twenty‐seven participating UK secondary care centres.
Sample Women aged ≥18 years with symptomatic fibroids who were considered to justify surgical treatment.
Methods In total, 157 women were randomised (in a 2:1 ratio): 106 to UAE and 51 to surgery (hysterectomy 42; myomectomy nine).
Main outcome measures Quality of life at 5 years, as assessed by the Short Form General Health Survey (SF‐36). Secondary measures included complications, adverse events and the need for further intervention.
Results There were no significant differences between groups in any of the eight components of the SF‐36 scores at 5 years (minimum P = 0.45). Symptom score reduction and patient satisfaction with either treatment was very high, with no group difference. Rates of adverse events were similar in both groups (19% embolization and 25% surgery; P = 0.40). The 5‐year intervention rate for treatment failure or complications was 32% (UAE arm) and 4% (surgery arm), respectively. The initial cost benefit of UAE over surgery at 12 months was substantially reduced because of subsequent interventions, with treatments being cost neutral at 5 years.
Conclusions We have found that UAE is a satisfactory alternative to surgery for fibroids. The less invasive nature of UAE needs to be balanced against the need for re‐intervention in almost a third of patients. The choice should lie with the informed patient.
Recent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of prediction errors plays a key role in learning and ...decision-making, is controlled by dopamine and contributes to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation with a placebo, a dopamine receptor agonist bromocriptine or a dopamine receptor antagonist sulpiride (dopamine study n = 59) and in patients with early psychosis (psychosis study n = 74: 20 participants with first-episode psychosis, 30 healthy controls and 24 participants with at-risk mental state attenuated psychotic symptoms). Behavioural computational modelling indicated that precision weighting of prediction errors benefits learning in health and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors, which signal surprise, relative to their precision in superior frontal cortex (replicated across studies, combined n = 133), which was perturbed by dopaminergic modulation, impaired in psychosis and associated with task performance and schizotypy (schizotypy correlation in 86 healthy volunteers). In contrast to our previous work, we did not observe significant precision-weighting of signed prediction errors, which signal valence, in the midbrain and ventral striatum in the healthy controls (or patients) in the psychosis study. We conclude that healthy people, but not patients with first-episode psychosis, take into account the precision of the environment when updating beliefs. Precision weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.
LOFAR FACET CALIBRATION Weeren, R. J. van; Williams, W. L.; Hardcastle, M. J. ...
The Astrophysical journal. Supplement series,
03/2016, Volume:
223, Issue:
1
Journal Article
Peer reviewed
Open access
ABSTRACT LOFAR, the Low-Frequency Array, is a powerful new radio telescope operating between 10 and 240 MHz. LOFAR allows detailed sensitive high-resolution studies of the low-frequency radio sky. At ...the same time LOFAR also provides excellent short baseline coverage to map diffuse extended emission. However, producing high-quality deep images is challenging due to the presence of direction-dependent calibration errors, caused by imperfect knowledge of the station beam shapes and the ionosphere. Furthermore, the large data volume and presence of station clock errors present additional difficulties. In this paper we present a new calibration scheme, which we name facet calibration, to obtain deep high-resolution LOFAR High Band Antenna images using the Dutch part of the array. This scheme solves and corrects the direction-dependent errors in a number of facets that cover the observed field of view. Facet calibration provides close to thermal noise limited images for a typical 8 hr observing run at ∼ 5 ″ resolution, meeting the specifications of the LOFAR Tier-1 northern survey.
We report the direct observation of resistive flow through a weak link in a weakly interacting atomic Bose-Einstein condensate. Two weak links separate our ring-shaped superfluid atomtronic circuit ...into two distinct regions, a source and a drain. Motion of these weak links allows for creation of controlled flow between the source and the drain. At a critical value of the weak link velocity, we observe a transition from superfluid flow to superfluid plus resistive flow. Working in the hydrodynamic limit, we observe a conductivity that is 4 orders of magnitude larger than previously reported conductivities for a Bose-Einstein condensate with a tunnel junction. Good agreement with zero-temperature Gross-Pitaevskii simulations and a phenomenological model based on phase slips indicate that the creation of excitations plays an important role in the resulting conductivity. Our measurements of resistive flow elucidate the microscopic origin of the dissipation and pave the way for more complex atomtronic devices.
ABSTRACT We present deep LOFAR observations between 120 and 181 MHz of the "Toothbrush" (RX J0603.3+4214), a cluster that contains one of the brightest radio relic sources known. Our LOFAR ...observations exploit a new and novel calibration scheme to probe 10 times deeper than any previous study in this relatively unexplored part of the spectrum. The LOFAR observations, when combined with VLA, GMRT, and Chandra X-ray data, provide new information about the nature of cluster merger shocks and their role in re-accelerating relativistic particles. We derive a spectral index of at the northern edge of the main radio relic, steepening toward the south to . The spectral index of the radio halo is remarkably uniform ( , with an intrinsic scatter of ). The observed radio relic spectral index gives a Mach number of , assuming diffusive shock acceleration. However, the gas density jump at the northern edge of the large radio relic implies a much weaker shock ( , with an upper limit of ). The discrepancy between the Mach numbers calculated from the radio and X-rays can be explained if either (i) the relic traces a complex shock surface along the line of sight, or (ii) if the radio relic emission is produced by a re-accelerated population of fossil particles from a radio galaxy. Our results highlight the need for additional theoretical work and numerical simulations of particle acceleration and re-acceleration at cluster merger shocks.
While dopamine systems have been implicated in the pathophysiology of schizophrenia and psychosis for many years, how dopamine dysfunction generates psychotic symptoms remains unknown. Recent ...theoretical interest has been directed at relating the known role of midbrain dopamine neurons in reinforcement learning, motivational salience and prediction error to explain the abnormal mental experience of psychosis. However, this theoretical model has yet to be explored empirically. To examine a link between psychotic experience, reward learning and dysfunction of the dopaminergic midbrain and associated target regions, we asked a group of first episode psychosis patients suffering from active positive symptoms and a group of healthy control participants to perform an instrumental reward conditioning experiment. We characterized neural responses using functional magnetic resonance imaging. We observed that patients with psychosis exhibit abnormal physiological responses associated with reward prediction error in the dopaminergic midbrain, striatum and limbic system, and we demonstrated subtle abnormalities in the ability of psychosis patients to discriminate between motivationally salient and neutral stimuli. This study provides the first evidence linking abnormal mesolimbic activity, reward learning and psychosis.
Previous efforts to report estimates of cancer incidence and mortality in India and its different parts include the National Cancer Registry Programme Reports, Sample Registration System cause of ...death findings, Cancer Incidence in Five Continents Series, and GLOBOCAN. We present a comprehensive picture of the patterns and time trends of the burden of total cancer and specific cancer types in each state of India estimated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 because such a systematic compilation is not readily available.
We used all accessible data from multiple sources, including 42 population-based cancer registries and the nationwide Sample Registration System of India, to estimate the incidence of 28 types of cancer in every state of India from 1990 to 2016 and the deaths and disability-adjusted life-years (DALYs) caused by them, as part of GBD 2016. We present incidence, DALYs, and death rates for all cancers together, and the trends of all types of cancers, highlighting the heterogeneity in the burden of specific types of cancers across the states of India. We also present the contribution of major risk factors to cancer DALYs in India.
8·3% (95% uncertainty interval UI 7·9–8·6) of the total deaths and 5·0% (4·6–5·5) of the total DALYs in India in 2016 were due to cancer, which was double the contribution of cancer in 1990. However, the age-standardised incidence rate of cancer did not change substantially during this period. The age-standardised cancer DALY rate had a 2·6 times variation across the states of India in 2016. The ten cancers responsible for the highest proportion of cancer DALYs in India in 2016 were stomach (9·0% of the total cancer DALYs), breast (8·2%), lung (7·5%), lip and oral cavity (7·2%), pharynx other than nasopharynx (6·8%), colon and rectum (5·8%), leukaemia (5·2%), cervical (5·2%), oesophageal (4·3%), and brain and nervous system (3·5%) cancer. Among these cancers, the age-standardised incidence rate of breast cancer increased significantly by 40·7% (95% UI 7·0–85·6) from 1990 to 2016, whereas it decreased for stomach (39·7%; 34·3–44·0), lip and oral cavity (6·4%; 0·4–18·6), cervical (39·7%; 26·5–57·3), and oesophageal cancer (31·2%; 27·9–34·9), and leukaemia (16·1%; 4·3–24·2). We found substantial inter-state heterogeneity in the age-standardised incidence rate of the different types of cancers in 2016, with a 3·3 times to 11·6 times variation for the four most frequent cancers (lip and oral, breast, lung, and stomach). Tobacco use was the leading risk factor for cancers in India to which the highest proportion (10·9%) of cancer DALYs could be attributed in 2016.
The substantial heterogeneity in the state-level incidence rate and health loss trends of the different types of cancer in India over this 26-year period should be taken into account to strengthen infrastructure and human resources for cancer prevention and control at both the national and state levels. These efforts should focus on the ten cancers contributing the highest DALYs in India, including cancers of the stomach, lung, pharynx other than nasopharynx, colon and rectum, leukaemia, oesophageal, and brain and nervous system, in addition to breast, lip and oral cavity, and cervical cancer, which are currently the focus of screening and early detection programmes.
Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.
Smoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. ...We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, (an archetypal generalized inflammatory marker) and/or IL-6 activity, as a potential explanation for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated reciprocal relationships of lifetime smoking with depression (OR
= 2.01, 95% CI 1.71-2.37, p < 0.001; OR
= 1.09, 95% CI 1.06-1.13, p < 0.001), CRP levels and IL-6 activity (OR
= 1.40, 95% CI 1.21-1.55, p < 0.001; OR
= 1.03, 95% CI 1.02-1.05, p < 0.001, OR
= 1.06 (1.03-1.09), p < 0.001). These associations were also supported by the majority of the robust MR methods performed. We did not find evidence for a reciprocal relationship between CRP levels (using > 500 genetic instruments for CRP) and depression (OR
= 1.01, 95% CI 0.99-1.04; OR
= 1.03, 95% CI 0.99-1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to measures of generalized inflammation, but we found evidence for an attenuation of the smoking-depression association in multivariable mendelian randomization when adjusting for IL-6 activity, suggesting that the IL-6 pathway may be at least in part responsible for the association of smoking and depression. Our study supports potential bidirectional causal associations between lifetime smoking and depression which may be at least in part explained by the IL-6 signalling pathway. The IL-6 pathway may represent a putative therapeutic target for smoking and to mitigate the effects of smoking on depression.
Sugira Muryango is a father-engaged early child development and violence-prevention home-visiting programme delivered by trained lay workers. This cluster-randomised trial evaluates whether families ...living in extreme poverty (Ubudehe 1, the poorest category in the Government of Rwanda's wealth ranking) who receive Sugira Muryango in combination with a government-provided social protection programme demonstrate greater responsive, positive caregiving, nutrition, care seeking, hygiene, and father involvement compared with control families receiving usual care (UC).
Using detailed maps, we grouped closely spaced villages into 284 geographic clusters stratified by the type of social protection programmes operating in the village clusters; 198 clusters met all enrolment criteria. Sugira Muryango was delivered to n = 541 families in 100 treatment clusters with children aged 6-36 months living in extreme poverty. We assessed changes in outcomes in intervention and n = 508 UC control families using structured surveys and observation. Analyses were intent to treat using mixed models to accommodate clustering.
Families receiving Sugira Muryango improved on core outcomes of parent-child relationships assessed using the Home Observation for Measurement of the Environment (Cohen's d = 0.87, 95% CI: 0.74, 0.99) and the Observation of Mother-Child Interaction (Cohen's d = 0.29, 95% CI: 0.17, 0.41). We also saw reductions in harsh discipline on items from the UNICEF MICS (OR = 0.30: 95% CI: 0.19, 0.47) and in violent victimisation of female caregivers by their partners (OR = 0.49, 95% CI: 0.24, 1.00) compared with UC. Moreover, children in families receiving SM had a 0.45 higher increase in food groups consumed in the past 24 h (Cohen's d = 0.35, 95% CI: 0.22, 0.47), increased care seeking for diarrhoea (OR = 4.43, 95% CI: 1.95, 10.10) and fever (OR = 3.28, 95% CI: 1.82, 5.89), and improved hygiene behaviours such as proper treatment of water (OR = 3.39, 95% CI: 2.16, 5.30) compared with UC. Finally, Sugira Muryango was associated with decreased caregiver depression and anxiety (OR = 0.58, 95% CI: 0.38, 0.88).
Sugira Muryango led to improvements in caregiver behaviours linked to child development and health as well as reductions in violence.
ClinicalTrials.gov number NCT02510313.
Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) ...provides a comprehensive assessment of morbidity and mortality from falls.
Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records.
Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622-5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5-9.8) per 100 000 which equated to 695 771 (644 927-741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897-17 636 830) YLLs, 19 252 699 (13 725 429-26 140 433) YLDs and 35 940 787 (30 185 695-42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age.
This study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.
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