Background: Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder, characterized by gradual loss of motor, verbal and social skills. This study describes the epidemiology and healthcare resource utilization (HCRU) of RTT in Ontario, Canada. Methods: RTT patients (≥ one ICD-10-CA code F84.2) were identified using data held at the Institute for Clinical Evaluative Sciences (ICES), between September 2018-August 2023. Incidence and prevalence rates from Ontario were extrapolated nationally using the Stats Can population estimates. Results: A total of 246 patients were indexed; 95% female, median age 21 years and 40% from central Ontario. There were 57 incident and 257 prevalent RTT cases identified in Ontario. National extrapolations estimated 175 incident and 613 prevalent RTT cases. Common comorbidities included developmental disability (85.4%) and epilepsy (49.6%). Patients frequently had outpatient visits (primary care 96.7%, specialists 86.6%), emergency department visits (76.8%) and inpatient hospitalizations (54.5%). Most patients (95.1%) had at least one public claim for all-cause medication. Disease-specific medication claims were for anti-infectives (69.1%) and anti-seizure medications associated with mood effects (65.0%). Conclusions: This study provides population-based estimates of RTT in Canada. Findings highlight the high burden of illness and HCRU of RTT and the opportunities to improve healthcare outcomes in this population.

Psychopathology is intergenerationally transmitted through both genetic and environmental mechanisms via heterotypic (cross-domain), homotypic (domain-specific), and general (e.g., “p-factor”) pathways. The current study leveraged an adopted-at-birth design, the Early Growth and Development Study (57% male; 55.6% White, 19.3% Multiracial, 13% Black/African American, 10.9% Hispanic/Latine) to explore the relative influence of these pathways via associations between adoptive caregiver psychopathology (indexing potential environmental transmission) and birth parent psychopathology (indexing genetic transmission) with adolescent internalizing and externalizing symptoms. We included composite measures of adoptive and birth parent internalizing, externalizing, and substance use domains, and a general “p-factor.” Age 11 adolescent internalizing and externalizing symptom scores were the average of adoptive parent reports on the Child Behavior Checklist (n = 407). Examining domains independently without addressing comorbidity can lead to incorrect interpretations of transmission mode. Therefore, we also examined symptom severity (like the “p-factor”) and an orthogonal symptom directionality score to more cleanly disentangle transmission modes. The pattern of correlations was consistent with mostly general transmission in families with youth showing comorbid internalizing and externalizing symptoms, rather than homotypic transmission. Findings more strongly supported potential environmental or evocative mechanisms of intergenerational transmission than genetic transmission mechanisms (though see limitations). Parent-specific effects are discussed.

Many key environmental, industrial and energy processes rely on controlling fluid transport within subsurface porous media. These media are typically structurally heterogeneous, often with vertically layered strata of distinct permeabilities – leading to uneven partitioning of flow across strata, which can be undesirable. Here, using direct in situ visualization, we demonstrate that polymer additives can homogenize this flow by inducing a purely elastic flow instability that generates random spatio-temporal fluctuations and excess flow resistance in individual strata. In particular, we find that this instability arises at smaller imposed flow rates in higher-permeability strata, diverting flow towards lower-permeability strata and helping to homogenize the flow. Guided by the experiments, we develop a parallel-resistor model that quantitatively predicts the flow rate at which this homogenization is optimized for a given stratified medium. Thus, our work provides a new approach to homogenizing fluid and passive scalar transport in heterogeneous porous media.

Fall panicum is the most prevalent and problematic weed in rice in Florida. Outdoor studies were conducted in 2021 to determine the effect of flooding on fall panicum growth and its ability to produce and develop panicles. Fall panicum at the two- to four-leaf and four- to six-leaf stages of development were flooded in stock tanks maintained at flooding depths of 0, 10, 15, 20, and 30 cm for 56 d. Plant height, number of tillers and leaves, leaf area, shoot biomass, root biomass, and panicle branches for both fall panicum leaf stages of development decreased with increasing flooding depth. Fall panicum flooded at the two- to four-leaf stage survived flood depth of 15 cm, whereas plants flooded at the four- to six-leaf stage survived and emerged from a flood depth of up to 20 cm. The 10-cm flood depth resulted in the tallest plants with more leaves, tillers, and leaf area for both growth stages. The probability of fall panicum survival and ability to produce panicles decreased as flood depth increased. Flood depth required for 50% survival for four- to six-leaf-stage plants was estimated to occur at 14 cm, whereas that for plants at the two- to four-leaf stage occurred at 12 cm. The flood depth required to reduce panicle branch production by 50% was estimated to be 15 and 20 cm for two- to four-leaf, and four- to six-leaf-stage plants, respectively. These results show that flooding >10 cm is required to significantly reduce fall panicum survival and ability to produce panicles. Since flood level in rice is usually maintained at an average of 10 cm, chemical weed control will be important to supplement flooding for effective control of fall panicum in rice.

Fall panicum is a problematic weed in cropping systems including rice in southern Florida. There is limited information on growth and reproductive ability of fall panicum in water-stressed environments. The objective of this study was to determine the effect of 12.5%, 25%, 50%, 75%, and 100% pot soil water content (SWC) levels on fall panicum growth and panicle branch production under greenhouse conditions. Fall panicum height, number of leaves, and tillers decreased over time as SWC decreased. Fall panicum height decreased by 65% and 50% at 12.5% and 25% SWC, respectively, relative to height achieved at 100% SWC. Plants at 50% to 100% SWC were able to achieve 50% tiller production within 31 to 43 d compared with 28 d at 25% SWC. The 50% tiller production was not reached at 12.5% SWC during the duration of the study. Fall panicum shoot and root biomass, total leaf area, and number of panicle branches per plant at 56 d after SWC treatment initiation decreased as SWC decreased. Fall panicum biomass decreased 83% to 85% and 66% to 68% at 12.5% and 25% SWC, respectively, relative to 100% SWC. Leaf area declined 79% and 65% at 12.5% and 25% SWC levels, respectively, compared to the 100% SWC. Fall panicum was able to produce panicles at all SWC levels, although the plant produced significantly fewer panicle branches as SWC decreased. Plants at 12.5% and 25% SWC produced 82% and 59% fewer panicle branches, respectively, compared with plants at 100% SWC. This study shows that SWC influences the growth and reproductive capacity of fall panicum. Although fall panicum did not reach its full growth potential at low SWC levels, it was able to survive and develop panicles, showing its ability to adapt and reproduce under dry conditions.

Wall cooling has substantial qualitative and quantitative effects on the development of instabilities and subsequent transition processes in hypersonic boundary layers (HBLs). A sequence of linear stability theory, nonlinear two-dimensional and three-dimensional direct numerical simulations is used to analyse Mach 6 boundary layers, with wall temperatures ranging from near-adiabatic to highly cooled conditions, where the second-mode instability is accompanied by radiation of energy. Decomposition of linear stability modes into their fluid-thermodynamic (acoustic, vortical and thermal) components shows that this radiation comprises both acoustic as well as vortical waves. Furthermore, in these cases, two-dimensional simulations show that the conventional ‘trapped’ nature of second-mode instability is ruptured. A quantitative analysis indicates that although the energy efflux of both acoustic and vortical components increases with wall cooling, the destabilization effect is much stronger and no significant abatement of pressure perturbations is realized. The direct impact of these mechanisms on the transition process itself is examined with high-fidelity simulations of three-dimensional second-mode wavepacket propagation. In the near-adiabatic HBL, the wavepacket remains trapped within the boundary layer and attenuates outside the region of linear instability. However, wavepackets in the cooled wall HBLs amplify and display nonlinear distortion, and transition more rapidly. The structure of the wavepacket also displays different behaviour; moderately cooled walls show bifurcation into a leading turbulent head region and a trailing harmonic region, while highly cooled wall cases display lower convection speeds and significant wavepacket elongation, with intermittent spurts of turbulence in the wake of the head region. This elongation effect is associated with a weakening of the lateral jet mechanism due to the breakdown of spanwise coherent structures. These features have a direct impact on wall loading, including skin friction and heat transfer. In moderately cooled walls, the spatially localized wall loading is similar to those in near-adiabatic walls, with dominant impact due to coherent structures in the leading turbulent head region. In highly cooled walls, the elongated near-wall streaks in the wake region of the wavepacket result in more than twice as large levels of skin friction and heat transfer over a sustained period of time.

The evolution of the potent second-mode instability in hypersonic boundary layers (HBLs) is examined holistically, by tracking its linear and nonlinear evolution, followed by its role in initiating transition and eventual breakdown of the HBL into a fully turbulent state. Linear stability theory is utilized to first identify the features of the second-mode wave after $FS$-synchronization. These are then employed in separate linearly and nonlinearly forced two-dimensional (2-D) and three-dimensional (3-D) direct numerical simulations (DNS). The nonlinear 2-D DNS shows saturation of the fundamental frequency, and the resulting superharmonics induce tightly braided ‘rope-like’ patterns near the generalized inflection point (GIP). The instability exhibits a second region of growth constituted by the fundamental frequency downstream of the primary envelope, which is absent in the linear scenario. Subsequent fully 3-D DNS identify this region as crucial in amplifying oblique instabilities riding on the 2-D second-mode ‘rollers’. This results in lambda vortices below the GIP, which are detached from the rollers in the inner boundary layer. Streamwise vortex-stretching results in a localized peak in length scales inside the HBL, eventually forming hairpin vortices. Spectral analyses track the transformation of harmonic peaks into a turbulent spectrum. The appearance of oblique modes at the fundamental frequency suggests that fundamental resonance is the most dominant mechanism of transition. The bispectrum reveals coupled nonlinear interactions between the fundamental and its superharmonics leading to spectral broadening, as well as traces of subharmonic resonance. The global forms of the fundamental and subharmonic modes show that the former disintegrate at the location of spanwise breakdown, beyond which the latter amplify. Statistical analyses of the near-wall flow field indicate an increase in large-scale ‘splatting’ motions immediately following transition, resulting in extreme skin-friction events, which equilibrate as turbulence sets in. Fundamental resonance results in complete breakdown of streamwise streaks in the lower log-layer, ultimately resulting in a fully turbulent HBL.

Polymer solutions are often injected in porous media for applications such as oil recovery and groundwater remediation. As the fluid navigates the tortuous pore space, elastic stresses build up, causing the flow to become unstable at sufficiently large injection rates. However, it is poorly understood how the spatial and temporal characteristics of this unstable flow depend on pore space geometry, which can vary widely between different porous media. We investigate this dependence by systematically varying the spacing between pore constrictions in a one-dimensional ordered array. We find that when the pore spacing is large, unstable eddies form upstream of each constriction, similar to observations of an isolated constriction. By contrast, when the pore spacing is sufficiently small, the flow in the different pores exhibits a surprising bistability, stochastically switching between two distinct unstable flow states. We hypothesize that this unusual behaviour arises from the interplay between elongation and relaxation of polymers as they are advected through the pore space. Consistent with this idea, we find that the flow state in a given pore persists for long times; moreover, flow states are strongly correlated between neighbouring pores. Thus, the characteristics of unstable flow are not determined just by injection conditions and the geometry of the individual pores, but also depend on the spacing between pores. Ultimately, these results help to elucidate the rich array of behaviours that can arise in polymer solution flow through porous media.

Discrete unstable modes of hypersonic laminar boundary layers, obtained from an eigenvalue analysis, provide insight into key transition scenarios. The character of such modes near the leading edge is often identified with the corresponding asymptotic free-stream behaviour of acoustic, vortical or entropic (thermal) content, which we designate fluid-thermodynamic (FT) components. In downstream regions, however, this direct one-to-one correspondence between discrete modes and FT components does not hold, since FT components interact in well-defined ways with the basic state and with each other (even under linear scenarios). In the present work, we perform an FT decomposition of discrete modes using momentum potential theory, to yield a physics-based analysis that complements linear stability theory in the linear regime, and seamlessly extends to the nonlinear domain where direct numerical simulations are appropriate. Linear and nonlinear saturated disturbance effects, different forcing types and wall thermal conditions are considered, with emphasis on phenomena occurring near stability-mode synchronization locations. The results show that, in the linear regime, each discrete mode contains all FT components, whose relative amplitudes vary with streamwise distance. Vortical components are always the largest, followed by thermal and acoustic components. These latter two show distinct fore and aft signatures near mode synchronization. The vortical component displays a series of rope-shaped recirculation-cell patterns across the generalized inflection point. However, both acoustic and thermal components display ‘trapped’ structures. The former contains an alternating monopole array between the wall and the critical layer, while the latter is confined to an undulating region between the wall and a wavy locus straddling the generalized inflection point. Nonlinear saturation in the region of Mack-mode growth further strengthens the rope-shaped structures in the vortical component and higher harmonics appear, whose form and location depend on the specific component. Wall cooling modifies the eigenfunctions such that the acoustic component accounts for more of its composition, consistent with its destabilization. Analysis of energy interactions among the FT components indicates that, even though the vorticity component is the largest, the thermal component induces the most significant source term for the growth of acoustic perturbations, possibly due to the trapped nature of both.

The conversion of Ca(OH)2 to CaO has been studied by X-ray diffraction techniques. When Ca(OH)2 crystals are heated in vacuo the conversion is oriented, but not when they are heated at atmospheric pressure. This difference is attributed to the lowering of the decomposition temperature in vacuo and consequent lower thermal vibration.

Field experiments were conducted on clay and clay loam soils at the International Rice Research Institute to investigate the effects of competition between upland rice (Oryza sativa L.) and varying populations of purple nutsedge (Cyperus rotundus L.) for nitrogen, moisture, and light on the grain yield of upland rice. ‘IR5’ was used in 1972, while the experimental line ‘IR442-2-58’ was used in 1973. Grain yields of ‘IR5’ and ‘IR442-2-58’ increased with 60 kg/ha of nitrogen, and decreased with increased purple nutsedge population. The application of nitrogen to weedy upland rice fields benefited the purple nutsedge more than the rice. Purple nutsedge and upland rice competed extensively for moisture and the competition was much more serious with increased nitrogen fertilization. Purple nutsedge competition reduced the light transmission ratio (LTR). The reduction was proportional to the increase in purple nutsedge population density. Reductions in the LTR were greater at higher nitrogen levels during the three seasons.

In experiments conducted at the International Rice Research Institute, Philippines, all commonly marketed formulations and derivatives of either [(4-chloro-o-tolyl)oxy]acetic acid (MCPA) or (2,4-dichlorophenoxy) acetic acid (2,4,D) performed in about the same way and were equally safe for use in controlling barnyardgrass [Echinochloa crusgalli (L.) Beauv.] and other annual weeds in transplanted rice (Oryza sativa L.). Eleven-day-old rice seedlings were more susceptible to amine salts of 2,4-D or MCPA than 21-day-old seedlings. Granular formulations of some chemicals were relatively less toxic than liquid formulations. The toxic effect of spraying the potassium salt of MCPA was less prolonged on the indica variety, IR22, than it was on the japonica variety, Chianung 242, which had delayed flowering and maturity.

Background: The KCNT1 gene encodes subunits of the Na+-activated K+ channel, widely expressed in the CNS. Mutations of this gene have been implicated in Malignant Migrating Partial Seizures of Infancy (MMPSI). This early-onset epileptic encephalopathy represents a challenge due to pharmacoresistance. The channel-specific mutation represents the potential for targeted pharmacotherapy. Quinidine is a partial antagonist of the KCNT1 encoded channel; patients with MMPSI have been reported to have responded to doses ranging 34.4/kg/d - 60mg/kg/d. We present a case of MMPSI with a KCNTI mutation (c.G1283A:p.R428Q) trialled on quinidine. Methods: Following ineffective trials of 6 anti-seizure medications, this patient was trialled on oral quinidine. This patient was titrated up to a dose of 52mg/kg/d. Twenty-four hour EEG monitoring prior to quinidine therapy, and at target dose were compared. Results: Prior to initiation of quinidine, this patient experienced 22 electrographic seizures over 24 hours. At target dose, this patient experienced greater than 70 seizures over 24 hours. Conclusions: Quinidine has previously been reported to be effective in patients with MMPSI with the same and different mutations. We report the second case of a patient with MMPSI and KCNT1 mutation R428Q with poor clinical response to quinidine.

Background: Hemimegalencephaly (HME) is a hamartomatous malformation of one cerebral hemisphere, resulting in refractory epilepsy, intellectual disability, and autistic features. Hemispherectomy is the definitive treatment, but there is risk of high morbidity and mortality, especially when done in early infancy. Various preclinical studies have shown that dysregulation of the mTOR pathway has an integral role in the development of various epilepsy syndromes, including tuberous sclerosis complex (TSC), focal cortical dysplasia and HME. Recently, mTOR inhibitors were proven to be effective in treating seizures in TSC. Methods: We present a case of a 6 day old female with refractory epilepsy despite the trial of 9 anti-seizure medications and the ketogenic diet. As the patient was awaiting epilepsy surgery, an mTOR inhibitor, rapamycin was initiated. Results: After 1 week of the initiation, she had over a 50% reduction in seizures. At two weeks, the parents felt that for the first time, she was making developmental gains. She also appeared brighter and more interactive. Due to her response to treatment, her hemispherectomy was deferred to when she is older, so there will be a decreased risk of complications from the surgery. Conclusions: This case exemplifies how mTOR inhibitors should be considered as a treatment option for patients with HME and refractory epilepsy.

Background: Perampanel (PER) is a new anti-seizure medication that inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors. It is available in Canada for children since 2014. It is important for physicians to be aware of the efficacy and tolerability of drugs in the post-marketing phase. Methods: We did a retrospective review of our experience with PER at BC Children’s Hospital. Patients on PER were identified. Clinical data, including demographics, efficacy, tolerability, adverse effects (AE) and retention rates were obtained by review of clinical records. Results: Of 24 patients pediatric patients prescribed PER, 21 (87%) had focal and three had symptomatic generalized epilepsy. Ten (42%) had greater than 50% reduction in seizures. In fifteen patients, (63%) PER was discontinued due to AE or poor response. Twelve (50%) had behavioral AE and eight (33%) had non-behavioral AE. PER was effective, at lower doses than required for adults. One third experienced serious AE. One patient experienced oculogyric crisis, not previously reported with PER. AE were not associated with high doses and were reversible. Possible risk factors for behavioral AE include behavioral problems with other medications and pre-existing behavioral co-morbidities. Conclusions: It is important for clinicians to be aware of and counsel patients about serious AE, particularly behavioral, when prescribing PER.