Staying self-regulated in the classroom: The role of children's executive functions and situational factors.

BACKGROUND: Self-regulation is crucial for children's learning and development. Several studies have explored children's inter-individual differences in self-regulation, but little is known about sources of intra-individual variation. AIMS: This study addressed the variability of children's self-regulation across typical classroom situations and how this might be associated with children's executive functions (EFs). SAMPLE: The study included 148 children (54.7% girls; Mage = 56.73 months). METHODS: Self-regulation was assessed with an observational measure in teacher-led and child-led activities within naturalistic classroom settings. Children's EFs were assessed with direct assessments at the start and end of the school year. RESULTS: Linear mixed-effect models showed that children demonstrated higher levels of self-regulation in child-led in comparison with teacher-led activities. Children with higher levels of EFs at the start of the school year showed less variation across teacher-led and child-led activities in comparison with children with lower levels of EFs. Regarding other aspects of the classroom context, neither the group size in which the activity took place nor which school subject it was focused on were associated with children's self-regulation. However, in teacher-led activities the type of interaction involved in the activity and the type of task influenced children's self-regulation. CONCLUSION: These results suggest that children who start school with higher levels of EFs are more able to adapt to different situations, highlighting the importance of fostering these skills in early childhood. In turn, children with lower levels of EFs may need additional support from teachers to remain self-regulated across different contexts.

Principles for Adapting Assessments of Executive Function across Cultural Contexts.

Direct assessments of executive functions (EFs) are increasingly used in research and clinical settings, with a central assumption that they assess "universal" underlying skills. Their use is spreading globally, raising questions about the cultural appropriateness of assessments devised in Western industrialized countries. We selectively reviewed multidisciplinary evidence and theory to identify sets of cultural preferences that may be at odds with the implicit assumptions of EF assessments. These preferences relate to motivation and compliance; cultural expectations for interpersonal engagement; contextualized vs. academic thinking; cultural notions of speed and time; the willingness to be silly, be incorrect, or do the opposite; and subject-matter familiarity. In each case, we discuss how the cultural preference may be incompatible with the assumptions of assessments, and how future research and practice can address the issue. Many of the cultural preferences discussed differ between interdependent and independent cultures and between schooled and unschooled populations. Adapting testing protocols to these cultural preferences in different contexts will be important for expanding our scientific understanding of EF from the narrow slice of the human population that has participated in the research to date.

Promoting person-centred care at the end of life.

Providing person-centred care that takes into account each patient's individual needs and priorities is crucial at the end of life. Nurses need to be aware of the main aspects of person-centred care, such as supporting shared decision-making, developing therapeutic nurse-patient relationships, and considering the patient's physical, psychological, social and spiritual needs. This article discusses the concept of person-centred care in the context of providing end of life care to patients and their families. It explains the benefits and barriers to providing person-centred end of life care, and outlines some of the areas that nurses and other healthcare professionals need to consider to promote effective care.

The Impact of COVID-19 on the Lives of Individuals With Multiple Sclerosis: 1 Year Into the Pandemic.

Background: The COVID-19 pandemic resulted in implementation of restrictive public health policies requiring people to limit or avoid interaction with others. These policies also had an economic impact. Individuals with multiple sclerosis (MS) already experience higher incidences of depression, anxiety, social isolation, and job loss, and the continuing pandemic may exacerbate these. Methods: Between November 2, 2020, and February 12, 2021, 233 individuals with MS completed the Hospital Anxiety and Depression Scale, the modified Medical Outcomes Study Social Support Survey, the Centers for Disease Control/National Institutes of Health Common Data Element Repository economic impact questions, and study team-designed questions about social and family relationships and adherence to public health policies. Results: Study participants reported high rates of mask wearing, good hand hygiene, and limited interactions with those outside their homes. They felt isolated from family they did not live with, friends, and coworkers. The frequency of conflicts with their spouses/partners increased "a little" among 20% of respondents, but overall relationships with housemates were "unchanged" or "a little better." Ninety-one percent of participants reported experiencing no financial impact. On the Hospital Anxiety and Depression Scale, 16.0% of 218 respondents reported depressive symptoms and 26.8% of 216 reported symptoms of anxiety above the commonly accepted clinically significant cutoff points. Only 3.4% of participants reported contracting SARS-CoV-2. Conclusions: During the first year of the pandemic, this study found no pronounced impact on the emotional, social, or economic stability of the individuals with MS it surveyed. It seems that these study participants adapted to the restrictions created by the pandemic and, by adhering to guidelines, protected themselves from contracting SARS-CoV-2.

Social support predicts sleep quality in people with multiple sclerosis during the COVID-19 pandemic.

BACKGROUND: Poor sleep quality is one of the most prominent patient-reported problems in people with multiple sclerosis (PwMS). The COVID-19 pandemic resulted in PwMS having less contact with physicians, therapists, support groups, and family, which led to decreased access to typical supports. The purpose of this study was to assess how social support impacted sleep quality during the COVID-19 pandemic in PwMS within the United States. METHODS: Anonymous surveys were utilized to gather data from February - May 2021 from 209 PwMS during their return appointments (face-to-face and virtual) at the University of Kansas Medical Center (KUMC)'s MS Clinic in the United States. SPSS 27 was used to run four regressions in order to determine if social support predicted sleep quality with and without the inclusion of covariates (age, education, disability, anxiety/depression). RESULTS: The results indicate that overall feelings of being socially supported predict sleep quality. Additionally, various facets of social support predict sleep quality, even when controlling for covariates. Interestingly, while depression and anxiety were significant predictors of sleep quality, those constructs do not attenuate the social support-sleep relationship. CONCLUSION: These findings will provide key information pertaining to the association between social support and sleep in PwMS during COVID-19 where typical supports were limited. Understanding the challenges facing those living with chronic illnesses, specifically PwMS, will help researchers and clinicians alike create interventions to promote social support in the midst of a global pandemic.

Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury.

Importance: In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. Objectives: To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. Design, Setting, and Participants: This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. Main Outcomes and Measures: The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Results: Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. Conclusions and Relevance: In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.

Performance of macroporous resins for debittering HLB-affected grapefruit juice and its impacts on furanocoumarin and consumer sensory acceptability.

About 90% of grapefruit in Florida are affected by Huanglongbing (HLB). HLB negatively affects the organoleptic properties of grapefruit juice because affected trees overproduce bitter secondary-metabolites, mostly naringin. The objective of this research was to remove naringin from HLB-affected grapefruit juice using microporous-adsorbents and to investigate how debittering affected narirutin, limonoids, bergamottin, and consumer acceptability. The adsorption kinetics of naringin on seven adsorbent resins obeyed pseudo-second order. PAD550 and PAD600 showed better static adsorption/desorption. Adsorption-isotherms on these resins were better fitted on Temkin-Pyzhev-model. On a fixed-bed-column packed with PAD550 resin, a slower loading rate increased its breakthrough volume before naringin in effluent reached its taste-threshold. In addition to naringin being reduced to below its taste-threshold, debittering significantly decreased the content of limonin, nomilin, and bergamottin. A consumer taste panel rated debittered and half-debittered juices higher for overall acceptability than the untreated. The half-debittered juice was ranked the most preferred while untreated was the least preferred.

Disability measurement in Multiple Sclerosis patients 55 years and older: What is the Expanded Disability Status Scale really telling clinicians?

BACKGROUND: The Expanded Disability Status Scale (EDSS) measures disease progression in Multiple Sclerosis (MS). EDSS changes are assumed to be due to worsening MS-related disability. Strict interpretation of this premise may include some normal findings as abnormal, inflating the disability score. Further, determining the cause of neurologic symptoms can be difficult in an older population with comorbid illness and polypharmacy. OBJECTIVE: To examine the association between EDSS, age, comorbidities and polypharmacy. METHODS: 106 people, 55 years and older, with and without MS were administered the EDSS and a validated comorbidity questionnaire. Polypharmacy was also assessed. RESULTS: Median EDSS scores were 6.0 in people with MS and 3.0 in people without MS. No participant in our cohort had an EDSS of 0. Higher EDSS scores were associated with older age and more polypharmacy. Pyramidal and cerebellar functional systems accounted for the largest percentage of unique variance between groups. CONCLUSION: Older individuals with and without MS demonstrated significant disability on the EDSS. These findings indicate that EDSS scores may be partially due to factors other than MS. Our understanding of disease course and disability may benefit from the development of normative EDSS scores to correct for these factors.

A Randomized Controlled Trial of Novel Loop Drainage Technique Versus Standard Incision and Drainage in the Treatment of Skin Abscesses.

OBJECTIVES: The objective was to compare the failure rate of incision and drainage (I&D) with LOOP technique versus I&D with standard packing technique in adults and children presenting to the emergency department (ED) with subcutaneous abscess. METHODS: This prospective, randomized controlled trial (NCT03398746) enrolled a convenience sample of patients presenting to two Level 1 trauma centers over 12 months with skin abscesses. Of 256 patients screened, 217 patients were enrolled, 109 randomized to I&D with packing (50%) and 108 (50%) to I&D with LOOP. The primary outcome was treatment failure defined by admission, IV antibiotics, or repeat drainage within 10-day follow-up. The secondary outcomes included ease of procedure, ease of care, pain, and satisfaction using a 10-point numeric rating scale. RESULTS: There were no differences in patient characteristics between groups. Follow-up data were available in 196 (90%). Treatment failure occurred in 20% (range = 12%-28%) of packing patients and 13% (range = 6%-20%) of LOOP patients (p = 0.25). There were no significant differences in failure rates in adults (p = 0.82), but there was a significant difference in children (age ≤ 18 years) at 21% (range = 8%-34%) in the packing group and 0 (0%) in the LOOP group (p = 0.002). Operators reported no significant differences in ease of procedure between techniques (p = 0.221). There was significantly less pain at follow-up in the LOOP group versus packing (p = 0.004). The wound was much easier to care for over the first 36 hours in the LOOP group (p = 0.002). Patient satisfaction at 10 days postprocedure was significantly higher in the LOOP group (p = 0.005). CONCLUSIONS: The LOOP and packing techniques had similar failure rates for treatment of subcutaneous abscesses in adults, but the LOOP technique had significantly fewer failures in children. Overall, pain and patient satisfaction were significantly better in patients treated using the LOOP technique.

Management of acute and chronic iliofemoral venous outflow obstruction: a multidisciplinary team consensus.

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

A data mining and item response mixture modeling method to retrospectively measure Diagnostic and Statistical Manual of Mental Disorders-5 attention deficit hyperactivity disorder in the 1970 British Cohort Study.

OBJECTIVE: To facilitate future outcome studies, we aimed to develop a robust and replicable method for estimating a categorical and dimensional measure of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) attention deficit hyperactivity disorder (ADHD) in the 1970 British Cohort Study (BCS70). METHOD: Following a data mining framework, we mapped DSM-5 ADHD symptoms to age 10 BCS70 data (N = 11,426) and derived a 16-item scale (α = 0.85). Mapping was validated by an expert panel. A categorical subgroup was derived (n = 594, 5.2%), and a zero-inflated item response theory (IRT) mixture model fitted to estimate a dimensional measure. RESULTS: Subgroup composition was comparable with other ADHD samples. Relative risk ratios (ADHD/not ADHD) included boys = 1.38, unemployed fathers = 2.07, below average reading = 2.58, and depressed parent = 3.73. Our estimated measures correlated with two derived reference scales: Strengths and Difficulties Questionnaire hyperactivity (r = 0.74) and a Rutter/Conners-based scale (r = 0.81), supporting construct validity. IRT model items (symptoms) had moderate to high discrimination (0.90-2.81) and provided maximum information at average to moderate theta levels of ADHD (0.5-1.75). CONCLUSION: We extended previous work to identify ADHD in BCS70, derived scales from existing data, modeled ADHD items with IRT, and adjusted for a zero-inflated distribution. Psychometric properties were promising, and this work will enable future studies of causal mechanisms in ADHD.

Preliminary report of histopathology associated with infection with tongue worms in Australian dogs and cattle.

Tongue worms utilise herbivorous mammals as intermediate hosts and reside in the nasopharynx of carnivores as their definitive hosts. A recent study in south eastern Australia showed an unexpectedly high infection (67%) of wild dogs with these parasites. The present study aimed at determining the pathogenicity of the parasite in both definitive (dog) and intermediate (cattle) hosts by histopathology. The definitive host showed multifocal haemorrhage of the interstitium of the nasal mucosa, multifocal mucosal erosion, congestion and haemorrhage, with haemosiderin laden macrophages present in those foci and distortion and destruction of the nasal mucosa. Histopathologic examination of lymph nodes from an infected cow showed diffuse eosinophilic granulomatous necrotising lymphadenitis and perinodal panniculitis with intralesional parasitic remnants and comparatively large numbers of eosinophils. A large, ~300-500 µm diameter, area of necrosis was also observed in one lymph node. This is the first time a study has been undertaken in Australia to determine the pathogenicity of tongue worms in both their definitive and intermediate hosts. This is a preliminary study and to properly estimate the health impact of infection with this pathogenic parasites on Australian production and companion animals more studies are necessary.

Culture-specific links between maternal executive function, parenting, and preschool children's executive function in South Korea.

BACKGROUND: Research on the relationships between parental factors and children's executive function (EF) has been conducted mainly in Western cultures. AIM: This study provides the first empirical test, in a non-Western context, of how maternal EF and parenting behaviours relate to child EF. SAMPLE: South Korean mothers and their preschool children (N = 95 dyads) completed EF tasks. METHOD: Two aspects of parental scaffolding were observed during a puzzle task: contingency (i.e., adjusting among levels of scaffolding according to the child's ongoing evidence of understanding) and intrusiveness (i.e., directive, mother-centred interactions). RESULTS AND CONCLUSIONS: Maternal EF and maternal contingency each accounted for unique variance in child EF, above and beyond child age, child language and maternal education. Maternal intrusiveness, however, was not significantly related to child EF. Additionally, no mediating role of parenting was found in the maternal and child EF link. However, child language was found to partially mediate the link between maternal contingency and child EF. These results complement prior findings by revealing distinctive patterns in the link between maternal EF, parenting behaviours, and child EF in the Korean context.

Examining Admission Factors Predicting Success in a Doctor of Nursing Practice Program.

BACKGROUND: Graduate nursing programs are challenged to select students who are likely to succeed and who add to nursing workforce diversity. METHOD: For this retrospective study, researchers examined 5 years of admission and retention data from a 4-year Bachelor-to-Doctor of Nursing Practice (DNP) program (n=144) at a large public midwestern university. Using a multinomial logistic regression analysis, four factors were examined to determine which predicted student success, delayed success, or failure: last 60-credit grade point average (GPA), admission essay score, average recommendation letter score, and demographic data (i.e., race, age, gender). RESULTS: GPA, age, and race were found to be significant predictors of student outcomes in this program. Writing and recommendation scores and gender did not predict student outcomes. CONCLUSION: DNP admission committees should consider the weight given to the GPA in their admission formulas and be prepared to work with retention committees to support older and minority students. [J Nurs Educ. 2018;57(1):49-52.].

Occurrence of tongue worm, Linguatula cf. serrata (Pentastomida: Linguatulidae) in wild canids and livestock in south-eastern Australia.

Pentastomids are obligate zoonotic arthropod parasites utilising canids and vulpids as their definitive hosts and several herbivorous species as their intermediate hosts. Reported only 10 times in Australia over the last 150 years as incidental findings, adult Pentastomids referred to as Linguatula serrata have been encountered in nasal cavities of domestic and wild dogs, and foxes. Nymphs have been reported in cattle and rabbits. In the present study, a number of potential definitive hosts, including red foxes (Vulpes vulpes), wild dogs (Canis lupus dingo and C.l. dingo x C. familiaris) and feral cats (Felis catus), and intermediate hosts cattle (Bos taurus), sheep (Ovis aries), feral pigs (Sus scrofa), rabbits (Oryctolagus cuniculus), goats (Capra hircus) and a European hare (Lepus europaeus), from the highlands of south-eastern Australia were examined. Of the animals examined 67.6% of wild dogs (n = 37), 14.5% of red foxes (n = 55) and 4.3% of cattle (n = 164) were found to be infected with Pentastomids, herein identified as Linguatula cf. serrata. The common occurrence of the parasite in wild dogs and less frequently in foxes suggests these wild canids have potential to act as a reservoir for infection of livestock, wildlife, domestic dogs and possibly humans. The unexpected high frequency of the parasite in wild dogs and foxes in south-eastern Australia suggests the parasite is more common than previously realised. Of the potential intermediate hosts in the region, only 4.3% of cattle were found to be infected with pentastomid nymphs which suggest the search for the host(s) acting as the main intermediate host in the region should continue. Future studies should investigate transmission patterns, health impacts on hosts and whether the parasite has zoonotic significance in Australia.

Processing of gaze direction within the N170/M170 time window: A combined EEG/MEG study.

Gaze direction is an important social signal for human beings. Beside the role of gaze in attention orienting, direct gaze (that is, gaze directed toward an observer) is a highly relevant biological stimulus that elicits attention capture and increases face encoding. Brain imaging studies have emphasized the role of the superior temporal sulcus (STS) in the coding of gaze direction and in the integration of gaze and head cues of social attention. The dynamics of the processing and integration of these cues remains, however, unclear. In order to address this question, we used deviated and frontal faces with averted and direct gaze in a combined electro- and magneto- encephalography (EEG-MEG) study. We showed distinct effects of gaze direction on the N170 and M170 responses. There was an interaction between gaze direction and head orientation between 134 and 162ms in MEG and a main effect of gaze direction between 171 and 186ms in EEG. These effects involved the posterior and anterior regions of the STS respectively. Both effects also emphasized the sensitivity to direct gaze. These data highlight the central role of the STS in gaze processing.

Bayesian change-point analysis reveals developmental change in a classic theory of mind task.

Although learning and development reflect changes situated in an individual brain, most discussions of behavioral change are based on the evidence of group averages. Our reliance on group-averaged data creates a dilemma. On the one hand, we need to use traditional inferential statistics. On the other hand, group averages are highly ambiguous when we need to understand change in the individual; the average pattern of change may characterize all, some, or none of the individuals in the group. Here we present a new method for statistically characterizing developmental change in each individual child we study. Using false-belief tasks, fifty-two children in two cohorts were repeatedly tested for varying lengths of time between 3 and 5 years of age. Using a novel Bayesian change point analysis, we determined both the presence and-just as importantly-the absence of change in individual longitudinal cumulative records. Whenever the analysis supports a change conclusion, it identifies in that child's record the most likely point at which change occurred. Results show striking variability in patterns of change and stability across individual children. We then group the individuals by their various patterns of change or no change. The resulting patterns provide scarce support for sudden changes in competence and shed new light on the concepts of "passing" and "failing" in developmental studies.

Contralateral breast cancer can represent a metastatic spread of the first primary tumor: determination of clonal relationship between contralateral breast cancers using next-generation whole genome sequencing.

INTRODUCTION: By convention, a contralateral breast cancer (CBC) is treated as a new primary tumor, independent of the first cancer (BC1). Although there have been indications that the second tumor (BC2) sometimes may represent a metastatic spread of BC1, this has never been conclusively shown. We sought to apply next-generation sequencing to determine a "genetic barcode" for each tumor and reveal the clonal relationship of CBCs. METHODS: Ten CBC patients with detailed clinical information and available fresh frozen tumor tissue were studied. Using low-coverage whole genome DNA-sequencing data for each tumor, chromosomal rearrangements were enumerated and copy number profiles were generated. Comparisons between tumors provided an estimate of clonal relatedness for tumor pairs within individual patients. RESULTS: Between 15-256 rearrangements were detected in each tumor (median 87). For one patient, 76 % (68 out of 90) of the rearrangements were shared between BC1 and BC2, highly consistent with what has been seen for true primary-metastasis pairs (>50 %) and thus confirming a common clonal origin of the two tumors. For most of the remaining cases, BC1 and BC2 had similarly low overlap as unmatched randomized pairs of tumors from different individuals, suggesting the CBC to represent a new independent primary tumor. CONCLUSION: Using rearrangement fingerprinting, we show for the first time with certainty that a contralateral BC2 can represent a metastatic spread of BC1. Given the poor prognosis of a generalized disease compared to a new primary tumor, these women need to be identified at diagnosis of CBC for appropriate determination of treatment. Our approach generates a promising new method to assess clonal relationship between tumors. Additional studies are required to confirm the frequency of CBCs representing metastatic events.

Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.

BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. RESULTS: The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS: Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. FUTURE WORK: Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51995477. 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. 19, No. 27. See the NIHR Journals Library website for further project information.