An examination of the factors connected with social, emotional and behavioural changes in Nurture Group pupils and an exploration of pupils' experiences

PhD ThesisThis review examined the effectiveness of Nurture Groups (NGs) for improving the SEBD of mainstream primary children by focusing on the primary review question, “What is known about the effectiveness of NGs to support pupils with social, emotional and behavioural difficulties in mainstream classrooms?” The review employed the seven stage methodology described by Petticrew and Roberts (2006) and initial screening achieved a systematic map of twenty studies. The refocusing of the review question into two separate questions allowed seven quantitative studies for the in-depth review. These studies were analysed according to an adapted framework by Cole (2008) and were synthesised on the basis of experimental design; outcomes and effectiveness and short term effects of NGs. All studies found evidence of significant short-term improvements in SEBD outcomes for mainstream NG children using reported scores on the Boxall Profile while the majority of studies found NGs to be effective directly post intervention using scores on the Strengths and Difficulties Questionnaire. These findings were consistent with the examination of effect sizes using data from three out of the seven studies which were in the medium to large range. As only one study provided follow-up data for the long term SEBD outcomes (Cooper and Whitebread, 2007), the review focused on short term effects and did not consider maintained change of NGs. Results are interpreted with caution due to variability in the methodological quality of studies and design limitations (very small sample sizes, lack of randomised control groups). The absence of commonality in statistical reporting also precludes any strong claims for the effectiveness of NGs from existing studies. The review concludes with suggestions for researchers, policy makers and those involved with NGs attempting to improve the SEBD outcomes for mainstream pupils

Differences in illness perceptions between patients with non-epileptic seizures and functional limb weakness

Objectives Illness perceptions play an important role in the onset and maintenance of symptoms in functional neurological symptom disorder (conversion disorder). There has, however, been little work examining differences between subtypes of this disorder. We therefore aimed to compare illness perceptions of patients with non-epileptic seizures (NES) and those with functional weakness (FW) with matching neurological disease controls to examine their specificity. Methods The Illness Perception Questionnaire Revised (IPQ-R) was completed by patients with functional limb weakness, non-epileptic seizures and patients with neurological disease causing limb weakness and epilepsy in two separate case control studies. Results Patients with FW (n=107), NES (= 40), Epilepsy (n=34) and neurological disease causing limb weakness (NDLW) (n=46) were included in the analysis. Both FW and NES patients reported a low level of personal control, understanding of their symptoms and a tendency to reject a psychological causation of their symptoms. However NES patients rejected psychological causes less strongly than FW patients (P<.01). Patients with NES were also more likely to consider their treatment to be more effective (P<.01). None of these differences appeared in a similar comparison between patients with epilepsy and patients with NDLW. Conclusion Although patients with NES tended, as a group, to reject psychological factors as relevant to their symptoms, they did so less strongly than patients with functional limb weakness in these cohorts. This has implications for both the way in which these symptoms are grouped together but also the way in which treatment is approached. Keywords Psychogenic non-epileptic seizures; Functional weakness; Conversion disorder; Epilepsy; Illness perception; Neurolog

Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants

There is increasing evidence that long-term outcomes for infants born prematurely are adversely affected by repeated exposure to noxious procedures. These interventions vary widely, for example, in the extent of damage caused and duration. NICU (neonatal intensive care unit) procedures are therefore likely to each contribute differently to the overall pain burden of individual neonates, ultimately having a different impact on their development. In order for researchers to quantify the procedural pain burden experienced by infants on NICU, we aimed to estimate the pain severity of common NICU procedures using published pain scores. We extracted pain scores over the first minute (pain reactivity) from the literature, using 59 randomized controlled trials for 15 different procedures. Hierarchical cluster analysis of average pain scores resulted in five discrete severity groups; mild (n=1), mild to moderate (n=3), moderate (n=7), severe (n=3) and very severe (n=1). The estimate of the severity of individual procedures provided new insight into infant pain reactivity which is not always directly related to the invasiveness and duration of a procedure; thus both heel lance and skin tape removal are moderately painful procedures. This estimate of procedural pain severity, based on pain reactivity scores, provides a novel platform for retrospective quantification of an individual neonate's pain burden due to NICU procedures. The addition of measures that reflect the recovery from each procedure, such as brain activity and behavioural regulation, would further improve estimates of the pain burden of neonatal intensive care

A developmental shift in habituation to pain in human neonates

Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates

Differences in relatives' and patients' illness perceptions in functional neurological symptom disorders compared with neurological diseases

Objective: The illness perceptions of the relatives of patients with functional neurological symptom disorders (FNSDs) and their relation to the illness perceptions of the patients have been little studied. We aimed to compare illness perceptions of relatives of patients with FNSDs with those held by patients themselves. We used control pairs with neurological diseases (NDs) to examine the specificity of the findings to FNSDs. Material and methods: Patients with FNSDs (functional limb weakness and psychogenic nonepileptic seizures) and patients with NDs causing limb weakness and epilepsy, as well as their relatives, completed adapted versions of the Illness Perception Questionnaire - Revised (IPQ-R). Results: We included 112 pairs of patients with FNSDs and their relatives and 60 pairs of patients with NDs and their relatives. Relatives of patients with FNSDs were more likely to endorse psychological explanations and, in particular, stress as causal factors than patients with FNSDs (p. <.001). Relatives of patients with FNSDs were also more pessimistic about the expected duration of the disorder and perceived a greater emotional impact compared with patients themselves (p. <.001). However, the latter two differences between patients and relatives were also found in pairs of patients with NDs and their relatives. Conclusion: The main difference in illness perceptions between relatives and patients that appeared specific to FNSDs was a tendency for relatives to see psychological factors as more relevant compared with patients. Some other differences were observed between pairs of patients with FNSDs and their relatives, but the same differences were also seen in pairs of patients with NDs and their relatives. These other differences were, therefore, not specific to FNSDs. Discussion about possibly relevant psychological factors with patients suffering from FNSDs may be helped by including relatives

Insights Into Elevated Distortion Product Otoacoustic Emissions In Sickle Cell Disease: Comparisons of Hydroxyurea-treated and Non-treated Young Children

Distortion product otoacoustic emissions (DPOAEs) were examined in 15 normal- hearing African-American children between the ages of 6 and 14 years with homozygous sickle cell disease (SCD), who were on a regimen of hydroxyurea (HDU), a drug that reduces inflammatory processes and symptoms of SCD; a matched group of 15 African- American children with homozygous SCD not on HDU; and 15 African-American children with normal hemoglobin. DPOAEs were evoked by 13 primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. Increased DPOAE amplitudes, believed to be a precursor of eventual hearing loss, were evident in children with SCD who were not receiving HDU. Those taking HDU had DPOAE amplitudes similar to normal controls. These findings suggest that HDU, in addition to reducing symptoms of SCD, may play a role in inhibiting or preventing cochlear pathology and hearing loss in individuals with SCD. Key Words: distortion product otoacoustic emissions; sickle cell disease; hydroxyurea Abbreviations: ABR = auditory brainstem response; DPOAE = distortion product otoacoustic emission; HDU = hydroxyurea; HbSS = homozygous sickle cell disease; ICAM = intercellular adhesion molecule; M = mean; OAE = otoacoustic emission; p = probability; PECAM = platelet-endothelial cell adhesion molecule SCD = sickle cell disease; SD = standard deviation of the mean; SOAE = spontaneous otoacoustic emission; TEOAE = transient evoked otoacoustic emission; VCAM = vascular cell adhesion molecule

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead