Background: To clarify the landscape of molecular diagnoses (MDs) in early-onset epilepsy individuals, we determined the prevalent MDs stratified by age at seizure onset (SO) and the time to MD in children with SO <36 months of life. Methods: A panel of up to 302 genes associated with epilepsy was utilized and ordering physicians provided the age of SO. Diagnostic yield analyses were performed for SO ages including <1 mo, 1-2 mo, 3-5 mo, 6-11 mo, 12-23 mo, and 24-35 mo. The time to MD (MD age - SO age) was determined for the top 10 genes in each SO category. Results: 15,074 individuals with SO <36 months of life were tested. Predominant MD findings are as follows: KCNQ2 in neonates with SO at <1mo, KCNQ2 and CDKL5 for SO between 1-2 mo, PRRT2 and SCN1A for SO between 3-11 mo, and SCN1A for SO between 12-36 months. The median time to MD varied by gene. For example, there was no delay in the median time to MD for the GLDC, KCNQ2, and SCN2A genes while the median delay for MECP2, SLC2A1, and other genes was ≥ 12 months. Conclusions: These data highlight the importance of comprehensive early testing in children with early-onset epilepsy.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

A 2012 American Heart Association statement concluded that children with CHD are at an increased risk for neurodevelopmental delays. Routine surveillance and evaluation throughout childhood are recommended. To assess paediatric cardiologist compliance with American Heart Association guidelines and developmental referral practices, a survey was distributed to paediatric cardiologists nationwide (n = 129). The majority of participants (69%) stated they were somewhat familiar or not familiar with the American Heart Association statement and were concerned about patients not being properly referred to specialists for developmental evaluation. Forty paediatric cardiologists (31%) indicated that their institution did not have a neurodevelopmental cardiology programme. Of these, 25% indicated they generally did not refer CHD patients for neurodevelopmental evaluation, 45% performed surveillance and referred if warranted, and 30% generally referred all patients for surveillance. Lastly, 43% of paediatric cardiologists did not feel responsible for developmental surveillance, and 11% did not feel responsible for referrals. To ensure all children with CHD are appropriately screened and referred, paediatricians and cardiologists must work together to address differing impressions of accountability for surveillance and screening of children with CHD.

Vitamin D, Ca and dairy products are negatively associated with colorectal cancer (CRC) incidence, but little is known of their influence on CRC survival. To investigate prediagnostic intakes of vitamin D, Ca and dairy products for their relevance to CRC prognosis, we analysed 504 CRC patients enrolled in the Newfoundland Colorectal Cancer Registry Cohort Study who were diagnosed for the first time with CRC between 1999 and 2003. Follow-up for mortality and cancer recurrence was through April 2010. Data on diet and lifestyle factors were gathered via a validated, semi-quantitative FFQ and a Personal History Questionnaire. Multivariate Cox models estimated hazard ratios (HR) and 95 % CI for the relationship of prediagnostic intakes of vitamin D, Ca and dairy products with all-cause mortality (overall survival, OS) and disease-free survival (DFS) among CRC patients. We found that prediagnostic Ca intake from foods, but not total Ca intake, was negatively associated with all-cause mortality (HR for Q2 v. Q1, 0·44; 95 % CI, 0·26, 0·75). An inverse relationship was also seen in a dose–response fashion for prediagnostic cheese intake (HR for Q4 v. Q1, 0·57, 95 % CI, 0·34, 0·95, Ptrend = 0·029). No evidence for modification by sex, physical activity, alcohol drinking and cigarette smoking was observed. In summary, high prediagnostic intakes of cheese and Ca from foods may be associated with increased survival among CRC patients. By manipulating diet, this study may contribute to the development of novel therapies that add to the armamentarium against CRC. Replication studies are required before any nutritional interventions are made available.

Exposure to childhood adversity is a powerful risk factor for psychopathology. Despite extensive efforts, we have not yet identified effective or scalable interventions that prevent the emergence of mental health problems in children who have experienced adversity. In this modified Delphi study, we identified intervention strategies for effectively targeting both the neurodevelopmental mechanisms linking childhood adversity and psychopathology – including heightened emotional reactivity, difficulties with emotion regulation, blunted reward processing, and social information processing biases, as well as a range of psychopathology symptoms. We iteratively synthesized information from experts in the field and relevant meta-analyses through three surveys, first with experts in intervention development, prevention, and childhood adversity (n = 32), and then within our study team (n = 8). The results produced increasing stability and good consensus on intervention strategy recommendations for specific neurodevelopmental mechanisms and symptom presentations and on strength of evidence ratings of intervention strategies targeting youth and parents. More broadly, our findings highlight how intervention decision making can be informed by meta-analyses, enhanced by aggregate group feedback, saturated before consensus, and persistently subjective or even contradictory. Ultimately, the results converged on several promising intervention strategies for prevention programming with adversity-exposed youth, which will be tested in an upcoming clinical trial.

We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (${\sim}2.8\,\mbox{K Jy}^{-1}$) low-system temperature (${\sim}18\,\mbox{K at }20\,\mbox{cm}$) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar $\mbox{J}0737{-}3039\mbox{A}$, pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR $\mbox{J}0540{-}6919$, and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR $\mbox{J}2241{-}5236$ exhibits a jitter limit of $<4\,\mbox{ns h}^{-1}$ whilst timing of PSR $\mbox{J}1909{-}3744$ over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.

We describe the design and deployment of GREENBURST, a commensal Fast Radio Burst (FRB) search system at the Green Bank Telescope. GREENBURST uses the dedicated L-band receiver tap to search over the 960–1 920 MHz frequency range for pulses with dispersion measures out to $10^4\ \rm{pc\,cm}^{-3}$. Due to its unique design, GREENBURST is capable of conducting searches for FRBs when the L-band receiver is not being used for scheduled observing. This makes it a sensitive single pixel detector capable of reaching deeper in the radio sky. While single pulses from Galactic pulsars and rotating radio transients will be detectable in our observations, and will form part of the database we archive, the primary goal is to detect and study FRBs. Based on recent determinations of the all-sky rate, we predict that the system will detect approximately one FRB for every 2–3 months of continuous operation. The high sensitivity of GREENBURST means that it will also be able to probe the slope of the FRB fluence distribution, which is currently uncertain in this observing band.

Difficulties with emotion regulation can take many forms, including increased sensitivity to emotional cues and habitual use of maladaptive cognitive or behavioral regulation strategies. Despite extensive research on emotion regulation and youth adjustment, few studies integrate multiple measures of emotion regulation. The present study evaluated the underlying structure of emotion regulation processes in adolescence using both task- and survey-based measures and determined whether differences in these emotion regulation latent factors mediated the association between peer victimization and internalizing psychopathology. Adolescents aged 16–17 years (n = 287; 55% female; 42% White) recruited in three urban centers in the United States completed baseline and follow-up assessments 4 months apart. Three models of emotion regulation were evaluated with confirmatory factor analysis. A three-factor model fit the data best, including cognitive regulation, behavioral regulation, and emotional reactivity latent factors. Task-based measures did not load onto these latent factors. Difficulties with behavioral regulation mediated the association between peer victimization and depression symptoms, whereas cognitive regulation difficulties mediated the association with anxiety symptoms. Findings point to potential targets for intervention efforts to reduce risk for internalizing problems in adolescents following experiences of peer victimization.