Background: Hypothalamic hamartomas (HH) are a challenging cause of seizure in children, partly because the neural circuitry involved in ictogenesis is incompletely understood. We review our institutions’ use of magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) to treat hypothalamic hamartoma (HH) with resting-state fMRI performed immediately before and after ablation. Methods: Seed-based whole brain connectivity to thalamic regions of interest was performed immediately pre- and post- MRgLITT. Multivariable generalized linear models were used to correlate resting-state data with seizure outcomes. Results: Eight patients underwent MRgLITT treatments for HH, with a mean follow up of 29 months. Four patients (50%) were seizure free at 12 months and two (25%) had a significant improvement in seizure frequency. We identified reduced thalamocortical connectivity involving the anterior cingulate and posterior parietal regions, consistent with disconnection of the mammillothalamic tract and interruption of Papez circuit. Large-scale thalamocortical connectivity changes were driven by children who subsequently became seizure free. Conclusions: Disconnection of the mammillothalamic tract and interruption of thalamic circuitry in patients undergoing MRgLITT for HH appears to be associated with improved seizure outcomes. The ability to assess network changes immediately post- MRgLITT could enable operative adjustments to be made mid-procedure to optimize seizure outcome in real time.

The Tilburg Frailty Indicator (TFI) is a validated tool for determining frailty in older adults. This study examined the validity and accuracy of the TFI Part B (TFI-B) in a North American context. Seventy-two individuals ≥ 65 years of age recruited from a rural geriatric medicine clinic completed a set of self-reported and performance-based measures, including TFI-B. Frailty level was determined using modified Fried’s Frailty Phenotype (FFP). Pearson correlation coefficients (r) assessed the concurrent relationships between the TFI-B and other measures. Accuracy of the TFI-B in classifying frailty level was assessed using assessing area under the curve (AUC). The TFI-B scores showed low correlations (r < 0.4) with gait speed and grip, suggesting that the TFI-B did not consider frailty as merely a physical problem. The AUC of 0.82 indicated that the TFI-B scores accurately classified frail versus non-frail individuals. The score of ≥ 5 on the TFI-B scores showed satisfactory sensitivity/specificity (73%/77%) and excellent negative predictive value (91.95%). This indicates that a TFI-B score of < 5 can be used to rule out frailty.

Injurious feather pecking in non-cage systems is a serious economic and welfare concern for the egg-producing industry. Here, we describe the first results from an ongoing collaborative project to improve range environment and welfare of laying hens (Gallus gallus domesticus) within the McDonald's Restaurants Ltd, UK supply base. The objective of this study was to investigate, in a commercial situation, the correlation between: i) proportion of range cover and ii) proportion of canopy cover, with plumage damage of end-of-lay hens. The assessment of plumage damage due to injurious feather pecking is a key animal-based welfare indicator for laying hens in non-cage systems. In 2007 and 2008, all laying-hen producers within the McDonald's Restaurants Ltd egg-supply base, were required to plant (if not present already), 5% of the total range area with blocks of trees ether side, and between 20-25 m from the laying hen house. Plumage damage at end of lay was positively correlated with mortality and flocks depleted in summer had less plumage damage at end of lay than flocks depleted in autumn or winter, possibly because of weather conditions at the time of placement. There was no correlation between the proportion (5-90%) of range cover and plumage damage at the end of lay, however, plumage damage was negatively correlated with percent of canopy cover within tree-planted areas. Providing a minimum of 5% tree cover, planted close to the house but with good canopy coverage, may be a feasible and practical method enabling producers to reduce plumage damage due to injurious feather pecking in their laying-hen flocks. Tree cover provision may also provide environmental benefits, such as soil stabilisation, reduced nutrient leaching and carbon sequestration.

Background: Infantile spasms (IS) is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. This is a retrospective case series of children with IS who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada. Methods: The records of 223 patients seen in the IS clinic were reviewed. Results: Nineteen patients met inclusion criteria. The etiology of IS was encephalomalacia in six patients (32%), malformations of cortical development in 11 patients (58%), atypical hypoglycaemic injury in one patient (5%), and partial hemimegalencephaly in one patient (5%). Nine patients (47%) underwent hemispherectomy and 10 patients (53%) underwent lobectomy/lesionectomy. Three patients (16%) underwent a second epilepsy surgery. Fifteen patients (79%) were considered ILAE Seizure Outcome Class 1 (completely seizure free; no auras). The percentage of patients who were ILAE Class 1 at most recent follow-up decreased with increasing duration of epilepsy prior to surgery. Developmental outcome was improved in 14/19 (74%) and stable in 5/19 (26%) patients. Conclusions: Our study found excellent seizure freedom rates and improved developmental outcomes following epilepsy surgery in patients with a history of IS with a structural lesion detected on MRI brain.

Background: Infantile spasms (IS) is an epileptic encephalopathy, characterized by epileptic spasms, hypsarrhythmia, and developmental regression. This is a retrospective case series detailing the experience in children with IS who have undergone epilepsy surgery at The Hospital for Sick Children (HSC). Methods: Records of 223 patients from HSC were reviewed. Patients were included if they had a current or previous history of IS with a lesion detected on MRI/PET scan who underwent epilepsy surgery. Results: Nineteen patients were included. The etiology of IS was encephalomalacia in six patients (32%), malformations of cortical development in 11 patients (58%), atypical hypoglycaemic injury in one patient (0.5%), and partial hemimegalencephaly in one patient (0.5%). The median age at the onset of IS was five months. The median age at surgery was 18 months. Nine patients (47%) underwent hemispherectomy and 10 patients (53%) underwent lobectomy/lesionectomy. Fifteen patients (79%) were considered ILAE Seizure Outcome Class 1. Developmental outcome was improved in 14/19 (74%) and stable in 5/19 (26%) patients. Conclusions: Even with a generalized EEG pattern such as hypsarrhythmia, patients should be considered for focal resective surgery. Early surgical intervention shortens the duration of active epilepsy thus limiting the potentially irreversible effects of on-going seizures.

This article reports on a new project to investigate the activities of early Homo sapiens in the area of the Chotts ‘megalake’ in southern Tunisia. Excavations in 2015 and 2019 at Oued el Akarit revealed one of a number of Middle Stone Age (MSA) horizons near the top of a long sequence of Upper Pleistocene deposits. The site identified as Oued el Akarit (Sondage 8) consists of lithic artefacts, bone fragments of large ungulates and pieces of ostrich eggshell. Many of the objects are burnt. Excavation of about nine square metres revealed that these were associated with a lightly trampled and combusted occupation surface. Amongst the identified artefacts were Levallois flakes some of which could be refitted, thereby indicating the generally undisturbed nature of the occupation. The lithic finds also included side scrapers and other tools diagnostic of the MSA but significantly no bifacial or tanged tools. OSL (Optically Stimulated Luminescence) dating of the sediments and AMS (Accelerator Mass Spectrometry) radiocarbon dating of ostrich eggshell have produced uncalibrated age determinations in the range 37,000–40,000 years ago, one of the youngest ages for MSA sites in the region. This is the first example of a securely dated later MSA occupation in a riparian environment in south-eastern Tunisia.

Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure in utero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) in utero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child’s behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.

A standard framework for business ethics views the inquiry as an application of major ethical theories to specific issues in business. As these theories are largely presented as being principled, the exercise therefore becomes one of applying general principles to business situations. Many adopting this standard approach have thus resisted the implementation of the most prominent development in ethical theory in recent history: that of particularism. In this article, I argue that particularist thinking has much to offer to business ethics and that standard resistance to particularist business ethics is based largely on misunderstandings. I do so by illustrating how the harbinger of particularism, W. D. Ross, countenances the practical wisdom of particularist ethics while being 1) invulnerable to standard objections to particularist business ethics and 2) compatible with the generalism of the standard approach. The Rossian business ethic is therefore one that the standard approach should be eager to include.

Poor school connectedness (SC), defined as students’ feelings of belonging, safety, and fairness at school, is a risk factor for negative psychosocial outcomes. Few studies have examined the specific relationship between SC and anxiety. This study examined the relation between SC and anxiety within a group of 114 clinically anxious youth (mean age = 10.82; SD = 2.93; 48.2% female; 70.2% White, non-Hispanic); age differences were also examined. Results indicated that SC was significantly negatively associated with age but unrelated to gender, race/ethnicity, socio-economic status, parent education, or presence of a comorbid disorder. Findings generally revealed that low SC was associated with greater total and domain specific anxiety. SC may play a unique role in the maintenance of global and domain specific anxiety symptoms.