Reinstated episodic context guides sampling-based decisions for reward.

How does experience inform decisions? In episodic sampling, decisions are guided by a few episodic memories of past choices. This process can yield choice patterns similar to model-free reinforcement learning; however, samples can vary from trial to trial, causing decisions to vary. Here we show that context retrieved during episodic sampling can cause choice behavior to deviate sharply from the predictions of reinforcement learning. Specifically, we show that, when a given memory is sampled, choices (in the present) are influenced by the properties of other decisions made in the same context as the sampled event. This effect is mediated by fMRI measures of context retrieval on each trial, suggesting a mechanism whereby cues trigger retrieval of context, which then triggers retrieval of other decisions from that context. This result establishes a new avenue by which experience can guide choice and, as such, has broad implications for the study of decisions

Stellar Population Diagnostics of Elliptical Galaxy Formation

Major progress has been achieved in recent years in mapping the properties of passively-evolving, early-type galaxies (ETG) from the local universe all the way to redshift ~2. Here, age and metallicity estimates for local cluster and field ETGs are reviewed as based on color-magnitude, color-sigma, and fundamental plane relations, as well as on spectral-line indices diagnostics. The results of applying the same tools at high redshifts are then discussed, and their consistency with the low-redshift results is assessed. Most low- as well as high-redshift (z~1) observations consistently indicate 1) a formation redshift z>~3 for the bulk of stars in cluster ETGs, with their counterparts in low-density environments being on average ~1-2 Gyr younger, i.e., formed at z>~1.5-2, 2) the duration of the major star formation phase anticorrelates with galaxy mass, and the oldest stellar populations are found in the most massive galaxies. With increasing redshift there is evidence for a decrease in the number density of ETGs, especially of the less massive ones, whereas existing data appear to suggest that most of the most-massive ETGs were already fully assembled at z~1. Beyond this redshift, the space density of ETGs starts dropping significantly, and as ETGs disappear, a population of massive, strongly clustered, starburst galaxies progressively becomes more and more prominent, which makes them the likely progenitors to ETGs.Comment: To appear on Annual Review of Astronomy & Astrophysics, Vol. 44 (2006). 46 pages with 16 figures. Replaced version includes updated references, few typos less, and replaces Fig. 11 and Fig. 16 which had been skrewed u

Self-Motion Holds a Special Status in Visual Processing

Agency plays an important role in self-recognition from motion. Here, we investigated whether our own movements benefit from preferential processing even when the task is unrelated to self-recognition, and does not involve agency judgments. Participants searched for a moving target defined by its known shape among moving distractors, while continuously moving the computer mouse with one hand. They thereby controlled the motion of one item, which was randomly either the target or any of the distractors, while the other items followed pre-recorded motion pathways. Performance was more accurate and less prone to degradation as set size increased when the target was the self-controlled item. An additional experiment confirmed that participant-controlled motion was not physically more salient than motion recorded offline. We found no evidence that self-controlled items captured attention. Taken together, these results suggest that visual events are perceived more accurately when they are the consequences of our actions, even when self-motion is task irrelevant

The new COSMIN guidelines confront traditional concepts of responsiveness

The recently published "COSMIN" guidelines aim to rate properties of outcome instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues are comparison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth: the CASSAVA multiple methods study

BACKGROUND: Around 60,000 babies are born preterm (prior to 37 weeks' gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). OBJECTIVE: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 'Mode of delivery for preterm infants'). METHODS: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). RESULTS: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26-32 weeks' gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. CONCLUSION: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. FUTURE WORK: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. LIMITATIONS: Certainty that a trial could be conducted can be determined only when it is attempted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12295730. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information

Impact of the introduction of a universal childhood influenza vaccination programme on influenza-related admissions to paediatric intensive care units in England

Introduction A universal childhood influenza vaccination programme was introduced in the UK in September 2013. We examine the impact of the gradual introduction of this programme on influenza-related paediatric intensive care unit (PICU) admission rates in England. Methods We extracted data on all influenza-related admissions to PICUs in England in resident children aged 0–15 years old between October 2003 and March 2017 from the Paediatric Intensive Care Audit Network (PICANet) database. We estimated influenza-associated PICU admission rates per 100 000 children by age group, sex and winter season (October to March), and used Poisson regression models to estimate incidence rate ratios (IRRs) in the winter seasons since the introduction of universal childhood vaccination compared with the two winters before the introduction of the programme (2011–2013). Results We identified 929 influenza-related PICU admissions among 873 children. 48.3% of admissions were among children aged less than 2 years old. The influenza-associated PICU admission rate was 1.32 per 100 000 children (95% CI 1.23 to 1.40). We identified a significant increase in influenza PICU admissions in the winters following the introduction of the universal childhood vaccination programme compared with the winters of 2010/2011–2012/2013 among children aged <5 years old: IRR 1.58 (1.05, 2.37) in children <1 year, 2.71 (1.43, 5.17) in 1 year-olds and 1.98 (1.18, 3.31) in children 2–4 years old. No significant difference was found among children aged 5–15 years. Conclusion The universal childhood influenza vaccination has not yet reduced the influenza-associated burden on PICUs in England during its early phase of introduction. Monitoring of influenza PICU admission rates needs to continue in England to assess the long-term impact of universal paediatric influenza vaccination. Linkage between PICANet and national infection surveillance databases would better enable such monitoring

Effects of acute fatigue on the volitional and magnetically-evoked electromechanical delay of the knee flexors in males and females

Neuromuscular performance capabilities, including those measured by evoked responses, may be adversely affected by fatigue; however, the capability of the neuromuscular system to initiate muscle force rapidly under these circumstances is yet to be established. Sex-differences in the acute responses of neuromuscular performance to exercise stress may be linked to evidence that females are much more vulnerable to ACL injury than males. Optimal functioning of the knee flexors is paramount to the dynamic stabilisation of the knee joint, therefore the aim of this investigation was to examine the effects of acute maximal intensity fatiguing exercise on the voluntary and magnetically-evoked electromechanical delay in the knee flexors of males and females. Knee flexor volitional and magnetically-evoked neuromuscular performance was assessed in seven male and nine females prior to and immediately after: (i) an intervention condition comprising a fatigue trial of 30-seconds maximal static exercise of the knee flexors, (ii) a control condition consisting of no exercise. The results showed that the fatigue intervention was associated with a substantive reduction in volitional peak force (PFV) that was greater in males compared to females (15.0%, 10.2%, respectively, p < 0.01) and impairment to volitional electromechanical delay (EMDV) in females exclusively (19.3%, p < 0.05). Similar improvements in magnetically-evoked electromechanical delay in males and females following fatigue (21%, p < 0.001), however, may suggest a vital facilitatory mechanism to overcome the effects of impaired voluntary capabilities, and a faster neuromuscular response that can be deployed during critical times to protect the joint system

Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2-a study protocol.

INTRODUCTION: The STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings. METHODS: STOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks' gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary).The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks' gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies.We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups. ANALYSIS: Data will be analysed on the intention-to-treat principle. ETHICS: STOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610. DISSEMINATION: Peer reviewed journals, presentations at national and international scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN98835694 and NCT02235181

Design and Synthesis of a Quintessential Self-Transmissible IncX1 Plasmid, pX1.0

DNA exchange in bacteria via conjugative plasmids is believed to be among the most important contributing factors to the rapid evolution- and diversification rates observed in bacterial species. The IncX1 plasmids are particularly interesting in relation to enteric bacteria, and typically carry genetic loads like antibiotic resistance genes and virulence factors. So far, however, a “pure” version of these molecular parasites, without genetic loads, has yet to be isolated from the environment. Here we report the construction of pX1.0, a fully synthesized IncX1 plasmid capable of horizontal transfer between different enteric bacteria. The designed pX1.0 sequence was derived from the consensus gene content of five IncX1 plasmids and three other, more divergent, members of the same phylogenetic group. The pX1.0 plasmid was shown to replicate stably in E. coli with a plasmid DNA per total DNA ratio corresponding to approximately 3–9 plasmids per chromosome depending on the growth phase of the host. Through conjugation, pX1.0 was able to self-transfer horizontally into an isogenic strain of E. coli as well as into two additional species belonging to the family Enterobacteriaceae. Our results demonstrate the immediate applicability of recent advances made within the field of synthetic biology for designing and constructing DNA systems, previously existing only in silica