Nuclear receptors and microRNAs: Who regulates the regulators in neural stem cells?

In this mini-review, we focus on regulatory loops between nuclear receptors and microRNAs, an emerging class of small RNA regulators of gene expression. Evidence supporting interactions between microRNAs and nuclear receptors in the regulation of gene expression networks is discussed in relation to its possible role in neural stem cell self renewal and differentiation. Furthermore, we discuss possible disturbances of the regulatory loops between microRNAs and nuclear receptors in human neurodegenerative disease. Finally, we discuss the possible use of nuclear receptors as pharmacological entry points to regulate neural stem cell self-renewal and differentiation

New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs

Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of the hippocampus and particularly the DG is impaired. For instance, adult neurogenesis is decreased with aging, in both proliferating and differentiation of newborn cells, while in parallel an age-associated decline in cognitive performance is often seen. Surprisingly, the synaptogenic potential of adult-born neurons is only marginally influenced by aging. Therefore, although proliferation, differentiation, and synaptogenesis of adult-born new neurons in the DG are closely related to each other, they are differentially affected by aging. In this review we discuss the crucial roles of a novel class of recently discovered modulators of gene expression, the small non-coding RNAs, in the regulation of adult neurogenesis. Multiple small non-coding RNAs are differentially expressed in the hippocampus. In particular a subgroup of the small non-coding RNAs, the microRNAs, fine-tune the progression of adult neurogenesis. This makes small non-coding RNAs appealing candidates to orchestrate the functional alterations in adult neurogenesis and cognition associated with aging. Finally, we summarize observations that link changes in circulating levels of steroid hormones with alterations in adult neurogenesis, cognitive decline, and vulnerability to psychopathology in advanced age, and discuss a potential interplay between steroid hormone receptors and microRNAs in cognitive decline in aging individuals

Piloting and producing a map of Millennium Cohort Study Data usage: Where are data underutilised and where is granularity lost?

The UK Millennium Cohort Study (MCS) is a longitudinal interdisciplinary study following the lives of 19,000 children born in the UK in 2000/1. Information has been collected at 9 months, 3, 5, 7 and 11 years, with the next sweep of data collection underway among study members who are aged 14 years. A wide range of data have been collected from children, parents and guardians, the partners of parents/guardians, older siblings and teachers, as well as sub-studies that collected data from health visitors; these include self-reported and objectively measured/verified data. This study sets out to examine how MCS data are utilised. To fit within the remit of the study, we hone in on ten priority question areas (Strengths and Difficulties Questionnaire, Child Social Behaviour Questionnaire, Diet, BMI, Immunisations, School Dis/like, Self-reported Friendships, Self-reported feelings, Screen Time, Hobbies). In total we found 481 unique studies that were using MCS data and undertaking primary analysis up to July 2015. Data that are collected through a recognised scale with defined thresholds or cut-off points for identifying constructs of interest and/or data that can provide a unique insight into a policy-relevant issue, are those most widely used in the MCS data. Measures that have been collected across sweeps – diet, BMI, SDQ and screen time - are all comparatively well used. Those measures that have started to be collected at age 7 (and first made available in 2010) have had lower usage. Data that were collected from the child’s own reports (e.g. friendships and feelings) have seldom been utilised in comparison to data collected through parental reports (e.g. SDQ). Collection of data from multiple informants did not always correlate with higher levels of usage. Imposing thresholds on data was found to be problematic in some cases, for example for BMI, where a number of different thresholds for overweight and obesity were in use. The use of different thresholds can lead to substantial differences in the results obtained. This is the first review using systematic methods that has explored MCS data use. We set out a number of ideas for good practice around the use of and reporting of MCS data

Cross-verification of independent quantum devices

Quantum computers are on the brink of surpassing the capabilities of even the most powerful classical computers. This naturally raises the question of how one can trust the results of a quantum computer when they cannot be compared to classical simulation. Here we present a verification technique that exploits the principles of measurement-based quantum computation to link quantum circuits of different input size, depth, and structure. Our approach enables consistency checks of quantum computations within a device, as well as between independent devices. We showcase our protocol by applying it to five state-of-the-art quantum processors, based on four distinct physical architectures: nuclear magnetic resonance, superconducting circuits, trapped ions, and photonics, with up to 6 qubits and 200 distinct circuits

Centralisation of services for children with cleft lip or palate in England: a study of hospital episode statistics.

BACKGROUND: In 1998, a process of centralisation was initiated for services for children born with a cleft lip or palate in the UK. We studied the timing of this process in England according to its impact on the number of hospitals and surgeons involved in primary surgical repairs. METHODS: All live born patients with a cleft lip and/or palate born between April 1997 and December 2008 were identified in Hospital Episode Statistics, the database of admissions to English National Health Service hospitals. Children were included if they had diagnostic codes for a cleft as well as procedure codes for a primary surgical cleft repair. Children with codes indicating additional congenital anomalies or syndromes were excluded as their additional problems could have determined when and where they were treated. RESULTS: We identified 10,892 children with a cleft. 21.0% were excluded because of additional anomalies or syndromes. Of the remaining 8,606 patients, 30.4% had a surgical lip repair only, 41.7% a palate repair only, and 28.0% both a lip and palate repair. The number of hospitals that carried out these primary repairs reduced from 49 in 1997 to 13, with 11 of these performing repairs on at least 40 children born in 2008. The number of surgeons responsible for repairs reduced from 98 to 26, with 22 performing repairs on at least 20 children born in 2008. In the same period, average length of hospital stay reduced from 3.8 to 3.0 days for primary lip repairs, from 3.8 to 3.3 days for primary palate repairs, and from 4.6 to 2.6 days for combined repairs with no evidence for a change in emergency readmission rates. The speed of centralisation varied with the earliest of the nine regions completing it in 2001 and the last in 2007. CONCLUSIONS: Between 1998 and 2007, cleft services in England were centralised. According to a survey among patients' parents, the quality of cleft care improved in the same period. Surgical care became more consistent with current recommendations. However, key outcomes, including facial appearance and speech, can only be assessed many years after the initial surgical treatment

Grommet Surgery in Children With Orofacial Clefts in England.

OBJECTIVE: To assess grommet insertion practice in the first 5 years of life among children with an orofacial cleft in England. DESIGN: Analysis of national administrative data of hospital admissions. SETTING: National Health Service hospitals, England. PATIENTS: Patients born between 1997 and 2005 who underwent surgical cleft repair. INTERVENTION: Children receiving grommets before the age of 5 years. OUTCOME MEASURES: The proportion of children receiving grommets before the age of 5 years, the timing of the first grommet insertion, and the proportion of children having repeat grommet insertions were examined according to cleft type, the absence or presence of additional anomalies, socioeconomic deprivation, and region of residence. RESULTS: The study included 8,269 children. Before the age of 5 years, 3,015 (36.5%) children received grommets. Of these, 33.2% received their first grommets at primary cleft repair and 33.3% underwent multiple grommet insertion procedures. The most common age for the first procedure was between 6 and 12 months. Children with a cleft affecting the palate were more likely to receive grommets than children with a cleft lip alone (45.5% versus 4.5%). Grommet insertion practice also varied according to year of birth, absence or presence of additional anomalies, socioeconomic deprivation, and region of residence. CONCLUSION: Grommets practice in children with a cleft appears to vary according to their clinical characteristics. The differences in practice observed according to deprivation and region of residence need to be further explored

Prevalence and severity of patient harm in a sample of UK-hospitalised children detected by the Paediatric Trigger Tool

The measurement and examination of adverse events (AEs) that occur in children during hospital admissions is essential if we are to prevent, reduce or ameliorate the harm experienced. The UK Paediatric Trigger Tool (UKPTT) is a method of retrospective case note review that measures harm in hospitalised children. Objectives: To examine the harm resulting from the processes of healthcare in hospitalised children from centres providing data to the National Health Service (NHS) Institute UKPTT data portal, to understand the positive predictive values of triggers and to make recommendations for the further development of the trigger tool. Setting: 25 hospitals across the UK, including secondary, tertiary and quaternary paediatric centres. Participants: Randomly selected children who were admitted to hospital for longer than 24 h. Outcome measures: The primary outcome measure was the rate of harm (the percentage of children experiencing one or more AEs during a hospital admission). Secondary measures were the severity of harm and performance of triggers. Results: Data from 3992 patient admissions were reviewed across the hospitals and submitted to the trigger tool portal from February 2008 to November 2011. At least one AE was reported for 567 (14.2%) patients, with 211 (5.3%) experiencing more than one event. There were 1001 AEs identified. Where harm occurred, it was considered temporary for 923 (92.2%) AEs; however, 43 (4.3%) AEs resulted in the need for life-sustaining interventions, 18 (1.8%) AEs led to permanent harm and for 17 children (1.7% of AEs) the AE was believed to have contributed to death. Conclusions: There is a significant, measurable level of harm experienced by children admitted to hospitals in the UK. While most of this harm is temporary, some of it is serious. The UKPTT offers organisations the means to measure and examine the AEs occurring in their hospital in order to reduce harm