Background: Tuberous Sclerosis Complex (TSC) is a multisystemic neurocutaneous disorder in which hamartomas confer significant medical risks, including mortality, by disruption of local tissues. However, only recently have multiple studies assessed specific aetiologies of mortality in TSC. Methods: A literature review of all available studies examining mortality in TSC was conducted until December 15, 2024. Results: We identified 13 studies reporting 411 deaths from 6735 individuals with TSC. Crude mortality per 100 individuals ranged from 1.4-13.8 over average intervals of 11-45 years. Mortality risk ranged from 3.0-4.9 (mean 4.3) versus the general population. Mean life expectancy was 66.2 years compared to 81.8 in the general population. In seven studies that reported specific aetiologies of mortality, 6/7 (85%) had renal (commonly renal failure or angiomyolipoma hemorrhage) or brain disease (most frequently sudden unexpected death in epilepsy or brain tumours) as the most common cause of mortality. Intellectual delay conferred increased mortality risk. Lymphangioleiomyomatosis conferred significant risk of mortality in adult women and cardiac rhabdomyomas were the dominant cause of neonatal mortality. Conclusions: Mortality in TSC is elevated compared to the general population, with brain and renal disease most frequently culpable. Future studies should assess the impact of disease modifying therapies on mortality in TSC.

Background: In Canada, individuals with intellectual disabilities (ID) make up approximately 25% of the epilepsy population. Despite making up only a small portion, adult hospitalization data in Canada shows that individuals with ID are significantly more likely to be seen in the ED, be hospitalized, and to die as a result of epilepsy and epilepsy complications, than individuals with typical cognitive development. Data looking at ED visits in adolescents with epilepsy and varying cognitive abilities is extremely limited. Methods: To address this, a retrospective chart review of 122 adolescents (42 MID and 80 typical cognitive development) with epilepsy between the ages of 14 and 18 was done. Results: Results showed that adolescents with typical cognitive development had significantly more ED visits (p=.006), and seizure related ED visits (p= .008) than adolescents with MID. Despite the reasons for ED visits not significantly differing between the two groups, adolescents with MID had significantly longer ED visits (p=.023). Finally, when looking exclusively at the MID group, results showed that females were significantly more likely to be seen at the ED than males (p=.001). Conclusions: Results suggest that ED visit frequencies differ among adults and adolescents with ID, potentially suggesting the presence of unique protective factors for adolescents.

The effect dietary FODMAPs (fermentable oligo-, di- and mono-saccharides and polyols) in healthy adults is poorly documented. This study compared specific effects of low and moderate FODMAP intake (relative to typical intake) on the faecal microbiome, participant-reported outcomes and gastrointestinal physiology. In a single-blind cross-over study, 25 healthy participants were randomised to one of two provided diets, ‘low’ (LFD) <4 g/d or ‘moderate’ (MFD) 14-18 g/d, for 3 weeks each, with ≥2-week washout between. Endpoints were assessed in the last week of each diet. The faecal bacterial/archaeal and fungal communities were characterised in 18 participants in whom high quality DNA was extracted by 16S rRNA and ITS2 profiling, and by metagenomic sequencing. There were no differences in gastrointestinal or behavioural symptoms (fatigue, depression, anxiety), or in faecal characteristics and biochemistry (including short-chain fatty acids). Mean colonic transit time (telemetry) was 23 (95% confidence interval: 15, 30) h with the MFD compared with 34 (24, 44) h with LFD (n=12; p=0.009). Fungal diversity (richness) increased in response to MFD, but bacterial richness was reduced, coincident with expansion of the relative abundances of Bifidobacterium, Anaerostipes, and Eubacterium. Metagenomic analysis showed expansion of polyol-utilising Bifidobacteria, and Anaerostipes with MFD. In conclusion, short-term alterations of FODMAP intake are not associated with symptomatic, stool or behavioural manifestations in healthy adults, but remarkable shifts within the bacterial and mycobiome populations were observed. These findings emphasise the need to quantitatively assess all microbial Domains and their interrelationships to improve understanding of consequences of diet on gut function.

Background: Prior to the pandemic, telemedicine use was limited and sparsely funded within Ontario. During the pandemic, a shift in clinical recommendations and government funding models promoted telemedicine. We aim to highlight both quantitative and qualitative aspects of the patient and provider experience over 2.5 years within a Canadian Pediatric Neurology clinic. Main objectives of the study are to assess the safety, efficiency and convenience of telemedicine. Methods: A REDCap survey was sent to all patients with a telemedicine appointment from March 2020 –September 2022 and all Pediatric Neurology providers. Survey included a 5-point Likert scale questions, open questions, and patient characteristics. Results: Responses received from 272 patients and 7 providers. 91% of patients and all providers were satisfied with telemedicine. 95% of patients and all providers felt they received or were able to provide safe/adequate care. 90% of patients and all providers reported that telemedicine was more convenient. 87% of patients and all providers were interested in future appointments via telemedicine. Conclusions: Our survey shows patients and providers had highly positive experiences with telemedicine – reporting care was adequate, safe, and more convenient. This data supports incorporating telemedicine into future care and advocates that Canadian regulations/billing codes to continue to support telemedicine.

Background: The Epilepsy Monitoring Unit (EMU) plays a crucial role in a patient’s diagnosis and management for seizures and epilepsy. The duration of stay required to obtain adequate information is not clear, especially in the pediatric population. In this study, we examine whether a one to four day length of stay in the EMU is sufficient to obtain the necessary information. Methods: Retrospective review of 522 admissions (2014-2021). Included any patient admitted to CHEO’s EMU for any length of time. Results: The average admission was 1.75 days with 35.7% of patients requiring repeat EMU visits. Through a binary logistic regression, we show that a previous diagnosis of refractory seizures increases the chance of readmission to the EMU. However, a diagnosis of refractory seizures is also associated with a higher chance of achieving admission goals. While other factors including seizure type, weaning of meds, goals of admission, age, and gender have no influence on likelihood of readmission or achieving admission goals. Conclusions: This study indicates that having a short admission for EMU monitoring is sufficient to capture enough data to achieve admission goals in the pediatric population.

Resistant starch 2 (RS2) may offer therapeutic value to irritable bowel syndrome (IBS) patients particularly in combination with minimally fermented fibre, but tolerability data are lacking. The present study evaluated the tolerability of RS2, sugarcane bagasse and their combination in IBS patients and healthy controls. Following baseline, participants consumed the fibres in escalating doses lasting 3 d each: RS2 (10, 15 and 20 g/d); sugarcane bagasse (5, 10 and 15 g/d); and their combination (20, 25 and 30 g/d). Gastrointestinal symptoms were assessed daily. Six IBS patients and five controls were recruited. No differences in overall symptoms from baseline were found across the fibre doses (IBS, P = 0⋅586; controls, P = 0⋅687). For IBS patients, all RS2 doses led to increased bloating. One IBS patient did not tolerate the low combination dose and another the high sugarcane bagasse dose. Supplementation of RS2 ≤ 20 g/d caused mild symptoms and was generally tolerated in IBS patients even when combined with minimally fermented fibre.

Background: Epilepsy is the most common chronic neurological illness worldwide, affecting more than 330, 000 people in Canada, 10, 000 of which reside in the Ottawa area. Despite facing higher mortality, stigma and social barriers, PLE (people living with epilepsy) incur treatment gaps even in high income countries like ours. Our goal was to address this burden locally with the creation of novel, community-integrated, care delivery for PLE in our area; we describe its inception. Methods: A transition program bridging pediatric and adult institutions was created to address the care continuity gap in 2017. Following a meeting of key stakeholders in the region in 2019, the community group was integrated into the model of care and the city-wide program was created incorporating adult, pediatric, transition and community pillars. A patient friendly website was launched in 2020 (ottawaepilepsyprogram.ca). Results: 170 patients were followed in the transition program since 2017. Adult and pediatric pillars have referred 70 patients to the community program between 2019-2020, 48 between 2020-2021. Through this, PLE are able to access the Clinic to community (C2C) and UPLIFT programs for social support services and mental health, respectively. Conclusions: An interconnected region-wide program can support PLE and foster innovative care integration across disciplines.

Background: The International League Against Epilepsy recommends patients with drug resistant epilepsy (DRE) be referred for surgical evaluation, however prior literature suggests this is an underutilized intervention. This study captures practices of North American pediatric neurologists regarding the management of DRE and factors which may promote or limit referrals for epilepsy surgical evaluation. Methods: A REDCap survey distributed via the Child Neurology Society mailing list to pediatric neurologists practicing in North America. “R” was used to conduct data analyses. Ethics approval from the CHEO REB was granted prior to the start of data collection. Results: 102 pediatric neurologists responded, 77% of whom currently practice in the United States. 73% of respondents reported they would refer a patient for surgical consultation after two failed medications. Of all potential predictors tested in a logistic regression model, low referral volume was the only predictor of whether participants refer patients after more than three failed medications. Conclusions: Pediatric neurologists demonstrate fair knowledge of formal recommendations to refer patients for surgical evaluation after two failed medication trials. Other modifiable factors reported, especially family perceptions of epilepsy surgery, should be prioritized when developing tools to enhance effective referrals and increase utilization of epilepsy surgery in the management of pediatric DRE.

The therapeutic value of specific fibres is partly dependent on their fermentation characteristics. Some fibres are rapidly degraded with the generation of gases that induce symptoms in patients with irritable bowel syndrome (IBS), while more slowly or non-fermentable fibres may be more suitable. More work is needed to profile a comprehensive range of fibres to determine suitability for IBS. Using a rapid in vitro fermentation model, gas production and metabolite profiles of a range of established and novel fibres were compared. Fibre substrates (n 15) were added to faecal slurries from three healthy donors for 4 h with gas production measured using real-time headspace sampling. Concentrations of SCFA and ammonia were analysed using GC and enzymatic assay, respectively. Gas production followed three patterns: rapid (≥60 ml/g over 4 h) for fructans, carrot fibre and maize-derived xylo-oligosaccharide (XOS); mild (30–60 ml/g) for partially hydrolysed guar gum, almond shell-derived XOS and one type of high-amylose resistant starch 2 (RS2) and minimal (no differences with blank controls) for methylcellulose, another high-amylose RS2, acetylated or butyrylated RS2, RS4, acacia gum and sugarcane bagasse. Gas production correlated positively with total SCFA (r 0·80, P < 0·001) and negatively with ammonia concentrations (r –0·68, P < 0·001). Proportions of specific SCFA varied: fermentation of carrot fibre, XOS and acetylated RS2 favoured acetate, while fructans favoured butyrate. Gas production and metabolite profiles differed between fibre types and within fibre classes over a physiologically relevant 4-h time course. Several fibres resisted rapid fermentation and may be candidates for clinical trials in IBS patients.

The lift and drag forces acting on a small spherical particle in a single wall-bounded linear shear flow are examined via numerical computation. The effects of shear rate are isolated from those of slip by setting the particle velocity equal to the local fluid velocity (zero slip), and examining the resulting hydrodynamic forces as a function of separation distance. In contrast to much of the previous numerical literature, low shear Reynolds numbers are considered ($10^{-3} \lesssim Re_{\gamma } \lesssim 10^{-1}$). This shear rate range is relevant when dealing with particulate flows within small channels, for example particle migration in microfluidic devices being used or developed for the biotech industry. We demonstrate a strong dependence of both the lift and drag forces on shear rate. Building on previous theoretical $Re_{\gamma } \ll 1$ studies, a wall-shear-based zero-slip lift correlation is proposed that is applicable when the wall lies both within the inner and outer regions of the disturbed flow. Similarly, we validate an improved wall-shear-based zero-slip drag correlation that more accurately captures the drag force when the particle is close to, but not touching, the wall. Application of the new correlations to predict the movement of a force-free particle shows that the examined shear-based lift force is as important as the previously examined slip-based lift force, highlighting the need to accurately account for shear when predicting the near-wall movement of force-free particles.

Early Palaeozoic crinoids are known only patchily from the British Isles except for accumulations at starfish beds. A single, exquisitely preserved crinoid is reported from the Telychian (Llandovery, Silurian) of the Pysgotwr Grits Formation of the Llangurig area, Powys, mid-Wales. This sedimentary succession is turbiditic in origin and poorly fossiliferous. The crinoid is a diplobathrid camerate, Euptychocrinus longipinnulus sp. nov., preserved as an external mould without counterpart. It has a high, shuttlecock-like crown; a conical, unsculptured cup; low infrabasals; a pair of long, slender, feather-like arms on each ray, each bearing numerous long pinnules; and a heteromorphic column. Most previous reports of this genus have been from the Upper Ordovician – lower Silurian series of Laurentia; uncertainly, it is described from the Upper Ordovician deposits of Morocco (Gondwana). Euptychocrinus longipinnulus is the first Avalonian occurrence. The beautiful preservation of the arms, including cover plates of pinnules, contrasts with the proxistele, which is a series of ‘broken sticks’. This crinoid responded to an adverse environmental fluctuation, probably a turbidity current, by autotomizing the stem, but it was carried downslope and buried alive.

Background: Tuberous sclerosis complex (TSC) is characterized by growth of benign tumors in the skin, brain, kidneys, lung and heart. Prognosis is mostly determined by the extent of brain involvement as tumors in the brain lead to seizures and cognitive problems. Epilepsy is highly associated with the cognitive abnormalities in TSC and recent evidence suggests anti-epileptic treatment before onset of seizures reduces epilepsy severity and risk of mental retardation. Screening and potential identification of TSC in utero via ultrasound would allow for prophylactic seizure management in these children. The sensitivity of antenatal ultrasound in the identification of brain abnormalities associated with TSC has not yet been published. In this case, we review the antenatal ultrasounds of a child with TSC for evidence of brain abnormalities in utero. Methods: Retrospective review Results: Retrospective review of antenatal ultrasounds showed some evidence of intracranial abnormalities. Ultrasound at 34 weeks and 4 days gestation revealed an echogenic density in the right ventricle that correlates with SEGA on post-natal MRI brain at 12 days of life. Post-natal brain ultrasound at 37 weeks revealed multiple cranial abnormalities not seen in utero. Conclusions: There are limitations to antenatal neurosonography in the detection of intracranial abnormalities associated with TSC.

Background: Fundoscopy is an important component of the neurological examination, but can be challenging in uncooperative children. This study explores whether playing a video during eye examination, improves the success, duration and ease of pediatric fundoscopy. Methods: We completed a prospective, multi-clinic, block-randomized trial. Patients 1-4 years were recruited in the emergency department, neurology, spinal cord and general pediatric clinic. Patients were randomized (by eye examined) to video/non-video assisted fundoscopy. Successful exams were defined as visualizing the fundus within 60 seconds. Time to visualize optic disc was recorded and difficulty of exam was examined using a 10-point Likert scale. Results: 101 subjects were recruited, with a mean age of 2.8 years. Overall, there was a 20% absolute improvement in the success rate of visualizing the optic disc in the video versus non-video group (p<0.01). Time to visualize optic disc was also improved (Δ5.3s, p<0.01). Improvement in ease of examination with video were noted by caregivers and practitioners (p<0.01). Conclusion: Playing a video improved the ease, duration and most importantly the success of fundoscopy in younger children. This simple, inexpensive adjunct has great potential to improve the ease and efficacy of this aspect of the neurological examination.

During the period from 1995 to 2011, radiocarbon measurements from the coast around Hartlepool in NE England have revealed anomalous enrichments in seawater, sediment, and marine biota. These cannot be explained on the basis of atomic weapons testing or authorized nuclear industry discharges, including those from the nearby advanced gas-cooled reactor. Enhanced 14C-specific activities have also been observed since 2005 in biota during routine monitoring at Hartlepool by the Food Standards Agency, but are reported as “likely” originating from a “nearby non-nuclear source.” Studies undertaken in Hartlepool and Teesmouth during 2005 and 2011 suggest that the 14C discharges are in the vicinity of Greatham Creek, with activity levels in biota analogous to those measured at Sellafield, which discharges TBq activities of 14C per annum. However, if the discharges are into Greatham Creek or even the River Tees, it is proposed that they would be much smaller than those at Sellafield and the high specific activities would be due to much smaller dilution factors. The discharge form of the 14C remains unclear. The activity patterns in biota are similar to those at Sellafield, suggesting that initial inputs are dissolved inorganic carbon (DI14C). However, the mussel/seaweed ratios are more akin to those found around Amersham International, Cardiff, which is known to discharge 14C in an organic form. 14C analysis of a sediment core from Seal Sands demonstrated excess 14C to the base of the core (43–44 cm). 210Pb dating of the core (0–32 cm) produced an accumulation rate of 0.7 g cm−2 yr−1, implying that 14C discharges have occurred from the 1960s until the present day.

From 1994 onwards, radiocarbon discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of northeast Irish Sea sediments would increase in 14C activity as mollusk shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and subtidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago.

Electroless (chemical) copper deposition, followed by electrolytic (galvanic) copper deposition, is used to construct electrical interconnects for electronic components on insulating substrate materials. As smooth substrates, such as glass or flexible materials like polyimide or polyethylene terephthalate, are used increasingly, achieving the required level of adhesion becomes more difficult. The film strain is one key variable that influences film adhesion. Standard X-ray diffraction based strain analysis was adapted for in situ strain monitoring during and after wet-chemical copper deposition. The results show that adding nickel suppresses an initial compressive strain that frequently appears in Ni-free baths. Adding ruthenium complexes to a standardized electroless copper formulation gradually shifts the strain from tensile to compressive. Spontaneous recrystallization at room temperature was monitored in detail for films obtained by direct current galvanic copper plating.