Moderate high temperature is beneficial or detrimental depending on carbon availability in the green alga Chlamydomonas reinhardtii.

High temperatures impair plant growth and reduce agricultural yields, but the underlying mechanisms remain elusive. The unicellular green alga Chlamydomonas reinhardtii is an excellent model to study heat responses in photosynthetic cells due to its fast growth rate, many similarities in cellular processes to land plants, simple and sequenced genome, and ample genetic and genomics resources. Chlamydomonas grows in light by photosynthesis and with externally supplied acetate as an organic carbon source. Understanding how organic carbon sources affect heat responses is important for the algal industry but remains understudied. We cultivated wild-type Chlamydomonas under highly controlled conditions in photobioreactors at 25 °C (control), 35 °C (moderate high temperature), or 40 °C (acute high temperature) with or without constant acetate supply for 1 or 4 day. Treatment at 35 °C increased algal growth with constant acetate supply but reduced algal growth without sufficient acetate. The overlooked and dynamic effects of 35 °C could be explained by induced acetate uptake and metabolism. Heat treatment at 40 °C for more than 2 day was lethal to algal cultures with or without constant acetate supply. Our findings provide insights to understand algal heat responses and help improve thermotolerance in photosynthetic cells.

Ethics and the Future of Meaningful Work: Introduction to the Special Issue.

The world of work over the past 3 years has been characterized by a great reset due to the COVID-19 pandemic, giving an even more central role to scholarly discussions of ethics and the future of work. Such discussions have the potential to inform whether, when, and which work is viewed and experienced as meaningful. Yet, thus far, debates concerning ethics, meaningful work, and the future of work have largely pursued separate trajectories. Not only is bridging these research spheres important for the advancement of meaningful work as a field of study but doing so can potentially inform the organizations and societies of the future. In proposing this Special Issue, we were inspired to address these intersections, and we are grateful to have this platform for advancing an integrative conversation, together with the authors of the seven selected scholarly contributions. Each article in this issue takes a unique approach to addressing these topics, with some emphasizing ethics while others focus on the future aspects of meaningful work. Taken together, the papers indicate future research directions with regard to: (a) the meaning of meaningful work, (b) the future of meaningful work, and (c) how we can study the ethics of meaningful work in the future. We hope these insights will spark further relevant scholarly and practitioner conversations.

High-throughput identification of novel heat tolerance genes via genome-wide pooled mutant screens in the model green alga Chlamydomonas reinhardtii.

Different high temperatures adversely affect crop and algal yields with various responses in photosynthetic cells. The list of genes required for thermotolerance remains elusive. Additionally, it is unclear how carbon source availability affects heat responses in plants and algae. We utilized the insertional, indexed, genome-saturating mutant library of the unicellular, eukaryotic green alga Chlamydomonas reinhardtii to perform genome-wide, quantitative, pooled screens under moderate (35°C) or acute (40°C) high temperatures with or without organic carbon sources. We identified heat-sensitive mutants based on quantitative growth rates and identified putative heat tolerance genes (HTGs). By triangulating HTGs with heat-induced transcripts or proteins in wildtype cultures and MapMan functional annotations, we presented a high/medium-confidence list of 933 Chlamydomonas genes with putative roles in heat tolerance. Triangulated HTGs include those with known thermotolerance roles and novel genes with little or no functional annotation. About 50% of these high-confidence HTGs in Chlamydomonas have orthologs in green lineage organisms, including crop species. Arabidopsis thaliana mutants deficient in the ortholog of a high-confidence Chlamydomonas HTG were also heat sensitive. This work expands our knowledge of heat responses in photosynthetic cells and provides engineering targets to improve thermotolerance in algae and crops.

'Single-handed care' initiatives and reviews of double-handed homecare packages: A survey of practices in English local authorities with adult social care responsibilities.

International health and social care systems are experiencing unprecedented pressure and demand. 'Single-handed care' initiatives seek to identify whether all or part of a homecare package involving more than one care worker can be safely reduced to a single worker. Little is known about these initiatives across local authorities. The aim of this study was to identify, describe and explain current processes and practices for single-handed care initiatives and double-handed homecare reviews. An electronic survey link was sent to each local authority with social care responsibilities in England. The questions covered a range of areas in relation to single-handed care processes and included a combination of pre-coded and free-text responses. Responses were received from 76 (50%) local authorities. Findings were that over 12,000 reviews were reported within a year with a median of 141 (IQR 45-280) from 53 authorities that provided figures. Reviews were usually led by a local authority occupational therapist. On average, 540 min was spent per review, including conducting and organising the review, documentation, and travel. In nearly half the authorities, double handed care remained at least partially in place following at least 80% of the reviews and remained wholly in place following at least 60%. Local authorities also reported some resistance from homecare providers when implementing single-handed care. The findings have confirmed anecdotal evidence that reviews of double-handed homecare packages are common practice within local authorities. Given the amount of time taken with these reviews, and paucity of evidence on outcomes for people receiving them, further research should evaluate this.

Animal hoarding cases in England: Implications for public health services.

Hoarding disorder is characterized by an accumulation of possessions due to excessive acquisition of or difficulty discarding possessions, regardless of their actual value and is estimated to affect 2-6% of the population. Animal hoarding, a distinct subset of hoarding disorder, has a significant public health impact on the humans involved, as well as animal welfare. Individuals exhibit self-neglect, apathy, social withdrawal and object hoarding; living within squalid, deteriorated, structurally unsafe and uninhabitable premises, alongside neglected animals. Cases are complex, costly and impact on a range of responding service providers. Effective case management is poorly understood and researched, with published literature in England particularly sparse. Improving understanding of the characteristics of these cases is the first step in informed case management. This research is the first exploration of the characteristics of animal hoarders in England and the areas where cases were located. Information about prosecutions involving large numbers of animals that were reported in the media was systematically obtained. This identified 66 cases between January 2015 and December 2020. Geospatial analysis exploring characteristics of locations where animal hoarding cases are also reported. Findings were broadly consistent with the international literature in that females (64%), those living alone (71%) and those with a mean age of 49 were well represented. Cats (61.5%) and dogs (60%) were the most commonly hoarded species. There was a mean of 44 animals per case and dead or animals requiring euthanasia found in 53% of cases. Key characteristics of the areas where cases were found highlight urban, densely populated, and high levels of deprivation being the most represented. Evidence of recidivism was evident in 39% of cases, suggesting that prosecution is not an effective rehabilitator. Animal hoarding raises serious implications for Public Health Services, and the lack of current effective case management strategies are discussed.

Nursing surveillance of respiratory adverse events among hospitalized adults: A systematic review to guide evidence-based practice.

BACKGROUND: Nursing surveillance (NS) involves the purposeful, ongoing acquisition, interpretation, and synthesis of patient data for clinical decision-making. Surveillance is used to identify patients with early signs of distress and prevent adverse events. The processes that support and measure the outcomes of nursing surveillance are not clearly specified. AIM: The aim of this systematic review was to describe the impact of NS on respiratory adverse events for adult hospitalized patients. METHODS: The PRISMA model guided this systematic search of Academic Search Complete (EBSCOhost), CINAHL Complete (EBSCOhost), Nursing & Allied Health (ProQuest), and PubMed databases for articles published between 1990 and 2019. Search terms included nursing surveillance, data points typically attributed to nursing surveillance, adult hospitalized patients, and adverse respiratory events. The protocol for this review was registered as PROSPERO: CRD42020147557. RESULTS: Of the 2907 references screened, 67 full-text articles were reviewed and 10 were eligible for inclusion. Research on nursing surveillance in the presence of respiratory deterioration is limited. Six studies used assessment tools that were generated from early warning scores, and four used research or institutionally designed trigger criteria. Surveillance, like other types of nursing care, was difficult to isolate and measure. Although components of surveillance were described in the selected studies, the nurse's role was not explicitly identified. Further research is required to highlight the role nursing surveillance plays in clinical decision-making to keep patients safe. LINKING EVIDENCE TO ACTION: The attributes of NS provide a useful intervention guide for the hospitalized patient at risk of deterioration. Early warning score techniques provide empirical evidence for identifying patients at risk of deterioration. The findings of this study provide evidence of the significance for research focused on the attributes of NS relative to responding to patients at risk of deterioration.

Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS.

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia.

OBJECTIVE: To determine whether 1-stage, limited corticectomy controls seizures in patients with MRI-positive, bottom-of-sulcus dysplasia (BOSD). METHODS: We reviewed clinical, neuroimaging, electrocorticography (ECoG), operative, and histopathology findings in consecutively operated patients with drug-resistant focal epilepsy and MRI-positive BOSD, all of whom underwent corticectomy guided by MRI and ECoG. RESULTS: Thirty-eight patients with a median age at surgery of 10.2 (interquartile range [IQR] 6.0-14.1) years were included. BOSDs involved eloquent cortex in 15 patients. Eighty-seven percent of patients had rhythmic spiking on preresection ECoG. Rhythmic spiking was present in 22 of 24 patients studied with combined depth and surface electrodes, being limited to the dysplastic sulcus in 7 and involving the dysplastic sulcus and gyral crown in 15. Sixty-eight percent of resections were limited to the dysplastic sulcus, leaving the gyral crown. Histopathology was focal cortical dysplasia (FCD) type IIb in 29 patients and FCDIIa in 9. Dysmorphic neurons were present in the bottom of the sulcus but not the top or the gyral crown in 17 of 22 patients. Six (16%) patients required reoperation for postoperative seizures and residual dysplasia; reoperation was not correlated with ECoG, neuroimaging, or histologic abnormalities in the gyral crown. At a median 6.3 (IQR 4.8-9.9) years of follow-up, 33 (87%) patients are seizure-free, 31 off antiseizure medication. CONCLUSION: BOSD can be safely and effectively resected with MRI and ECoG guidance, corticectomy potentially being limited to the dysplastic sulcus, without need for intracranial EEG monitoring and functional mapping. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that 1-stage, limited corticectomy for BOSD is safe and effective for control of seizures.

Clinical seizure manifestations in the absence of synaptic connections.

We report a child with a history of temporal-parietal-occipital disconnection for epilepsy secondary to posterior quadrantic dysplasia who developed recurrent and prolonged bouts of distress and autonomic disturbance associated with EEG and PET evidence of status epilepticus confined to his disconnected cortex. These bouts were refractory to antiseizure medications but resolved following resection of the disconnected cortex. In the absence of synaptic connections, we hypothesise that his seizure-related symptoms were mediated either by neurochemical transmission in preserved vascular and lymphatic channels or by ephaptic transmission to trigeminal nerve fibres in overlying dura, producing symptoms akin to migraine. The case highlights potential means by which seizures may manifest clinically, without synaptic connections, and adds to the differential for symptoms post-disconnection surgery.

The meaning of rehabilitation: a qualitative study exploring perspectives of occupational therapists and physiotherapists working with older people in acute care.

OBJECTIVE: To explore how occupational therapists and physiotherapists constructed and interpreted the meaning of rehabilitation in relation to older people in acute care. DESIGN: A focussed ethnographic study was undertaken, primarily using observation, interviewing and review of clinical records within one acute medical ward in a general hospital in the UK. Five patient participants gave consent for their episode of care to be studied, with observations and interviews primarily involving the identified patients and five occupational therapy and physiotherapy professionals. RESULTS: Four themes were identified: rehabilitation as a process to facilitate physical improvement; rehabilitation as physiotherapy-led; rehabilitation as a place…but not here; and rehabilitation as a process which prioritises safety over function. Such conceptualisations of rehabilitation were recognised as rooted in social and historical perceptions and challenged the ideals of rehabilitation professionals. CONCLUSIONS: The meaning of rehabilitation in acute care is shaped by a range of cultural, contextual and systemic influences. Recognising these influences, and subsequent challenges to rehabilitation ideals, can encourage professionals to work towards meaningful change.Implications for RehabilitationA reductionist version of rehabilitation was evident within this context which placed value on physical improvement, achieving optimum safety and led by physiotherapy.This version of rehabilitation was unsatisfactory to occupational therapists and physiotherapists in this setting and different to their ideals.Where rehabilitation may be associated with another place, practitioners should reflect on whether this is influencing patients becoming a lower priority for interventions whilst waiting and address this, if required, within their own reasoning, prioritisation and delegation.Those who recognise similarities with their own practice context could individually, and within teams, revisit definitions of rehabilitation to notice, document and have conversations about the ideals of their professions versus the reality of practice.Occupational therapists and physiotherapists can be champions for organisational and cultural change to promote rehabilitation as a multi-disciplinary phase of care working towards optimising improvements in wellbeing, function and safety, irrespective of location.

Views and experiences of visually impaired older people and exercise instructors about the Falls Management Exercise programme: a qualitative study.

PURPOSE: To gain insight into visually impaired older people's views regarding acceptability of an adapted Falls Management Exercise programme, and to explore Postural Stability Instructors's perspectives on provision of the programme. MATERIALS AND METHODS: Data from this qualitative study comprised interviews with nine visually impaired older people and two Postural Stability Instructors. Data were analysed using thematic analysis. RESULTS: Themes identified from interviews with the participants related to self-perception, exercise-related factors and facilitators to participation. Participants positioned themselves as not old or at risk of falls, felt exercises were not challenging enough and recommended that home exercise materials be offered in individually tailored formats. Themes identified from interviews with the instructors related to programme adaptations for visual impairments, exercises and facilitators to participation. Instructors recommended stratifying groups into levels of ability. Social time after the exercise sessions was deemed key in programme adherence by both participants and instructors. CONCLUSIONS: Visually impaired older people have similar barriers and facilitators to group-based falls prevention sessions as older people without visual impairment, but seem to have more difficulties in motivation to exercise at home. Both participants and instructors felt the main facilitator to adherence to group exercise sessions was the social time.Implications for rehabilitationVisually impaired older people have similar barriers and facilitators to group-based falls prevention sessions as older people without visual impairment, but seem to have more difficulties in motivation to exercise at home.Key recommended adaptations for falls prevention interventions in visually impaired older people include offering individually-tailored home exercise materials, stratifying groups into level of ability and involving social time.The social time after the exercise sessions was key in programme adherence.

Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19: a prospective observational study.

BACKGROUND: In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS. METHODS: In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2). FINDINGS: Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) was 18 kpa (IQR 15-21) and acute physiology and chronic health evaluation II score was 12 (10-16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO2/FiO2. The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01-0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS. INTERPRETATION: In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model. FUNDING: US National Institutes of Health, Innovate UK, and Randox.

Combined Isoflurane-Remifentanil Anaesthesia Permits Resting-State fMRI in Children with Severe Epilepsy and Intellectual Disability.

Head motion is a significant barrier to functional MRI (fMRI) in patients who are unable to tolerate awake scanning, including young children or those with cognitive and behavioural impairments. General anaesthesia minimises motion and ensures patient comfort, however the optimal anaesthesia regimen for fMRI in the paediatric setting is unknown. In this study, we tested the feasibility of anaesthetised fMRI in 11 patients (mean age = 9.8 years) with Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy associated with intellectual disability. fMRI was acquired during clinically-indicated MRI sessions using a synergistic anaesthesia regimen we typically administer for epilepsy neurosurgery: combined low-dose isoflurane (≤ 0.8% end-tidal concentration) with remifentanil (≤ 0.1 mcg/kg/min). Using group-level independent component analysis, we assessed the presence of resting-state networks by spatially comparing results in the anaesthetised patients to resting-state network templates from the 'Generation R' study of 536 similarly-aged non-anaesthetised healthy children (Muetzel et al. in Hum Brain Mapp 37(12):4286-4300, 2016). Numerous resting-state networks commonly studied in non-anaesthetised healthy children were readily identifiable in the anaesthetised patients, including the default-mode, sensorimotor, and frontoparietal networks. Independent component time-courses associated with these networks showed spectral characteristics suggestive of a neuronal origin of fMRI signal fluctuations, including high dynamic range and temporal frequency power predominantly below 0.1 Hz. These results demonstrate the technical feasibility of anaesthetised fMRI in children, suggesting that combined isoflurane-remifentanil anaesthesia may be an effective strategy to extend the emerging clinical applications of resting-state fMRI (for example, neurosurgical planning) to the variety of patient groups who may otherwise be impractical to scan.

Focal cortical hypermetabolism in atypical benign rolandic epilepsy.

OBJECTIVE: Atypical benign rolandic epilepsy (BRE) is an underrecognized and poorly understood manifestation of a common epileptic syndrome. Most consider it a focal epileptic encephalopathy in which frequent, interictal, centrotemporal spikes lead to negative motor seizures and interfere with motor and sometimes speech and cognitive abilities. We observed focal cortical hypermetabolism on PET in three children with atypical BRE and investigated the spatial and temporal relationship with their centrotemporal spikes. METHODS: EEG, MRI and PET were performed clinically in three children with atypical BRE. The frequency and source localization of centrotemporal spikes was determined and compared with the location of maximal metabolic activity on PET. RESULTS: Cortical hypermetabolism on thresholded PET t-maps and current density reconstructions of centrotemporal spikes overlapped in each child, in the central sulcus region, the distances between the "centers of maxima" being 2 cm or less. Hypermetabolism was not due to recent seizures or frequent centrotemporal spikes at the time of FDG uptake. SIGNIFICANCE: The findings suggest that localized, increased cortical activity, in the region of the EEG focus, underlies the negative clinical manifestations of atypical BRE. Similar findings are reported in the broader group of epileptic encephalopathies associated with electrical status epilepticus in sleep.

The hidden impact of home adaptations: Using a wearable camera to explore lived experiences and taken-for-granted behaviours.

Most adults over 65 years old live in mainstream housing in the United Kingdom, yet these can often be unsuitable for an individual's needs. With increased understanding of the relationship between housing, and health and well-being, the importance of modifying the home to suit individuals is recognised as being paramount. However, it is often difficult to monitor the ways in which home adaptations and equipment are used in the home. This study used innovative wearable technology to explore everyday, lived experiences of using home adaptations and equipment. Six older adults who had received a major home adaptation in the last 24 months took part in this study. Each participant used a wearable camera for one day and participated in a semi-structured interview while watching the images back as a 'slideshow'. Using this novel approach, three themes were generated from the data: acquiring adaptations and equipment, adapting routine and changing behaviour, and inconsistent and unintended uses. The findings of this study open up the complexity of the lived experience of using home adaptations and equipment. Experiences from access to long-term outcomes are personal, and individuals modify and use the adaptations in various ways to suit their own needs. The wearable camera allowed additional insight into lived experience that would otherwise not have been captured without its use, as the photographs acted as a way of stimulating conversation and highlighting taken-for-granted behaviours not often consciously considered by the individuals.

The epileptic network of Lennox-Gastaut syndrome: Cortically driven and reproducible across age.

OBJECTIVE: To identify brain regions underlying interictal generalized paroxysmal fast activity (GPFA), and their causal interactions, in children and adults with Lennox-Gastaut syndrome (LGS). METHODS: Concurrent scalp EEG-fMRI was performed in 2 separately analyzed patient groups with LGS: 10 children (mean age 8.9 years) scanned under isoflurane-remifentanil anesthesia and 15 older patients (mean age 31.7 years) scanned without anesthesia. Whole-brain event-related analysis determined GPFA-related activation in each group. Results were used as priors in a dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing initiation and propagation of GPFA between cortex, thalamus, and brainstem. RESULTS: A total of 1,045 GPFA events were analyzed (cumulative duration 1,433 seconds). In both pediatric and older groups, activation occurred in distributed association cortical areas, as well as the thalamus and brainstem (p < 0.05, corrected for family-wise error). Activation was similar across individual patients with structural, genetic, and unknown etiologies of epilepsy, particularly in frontoparietal cortex. In both groups, DCM revealed that GPFA was most likely driven by prefrontal cortex, with propagation occurring first to the brainstem and then from brainstem to thalamus. CONCLUSIONS: We show reproducible evidence of a cortically driven process within the epileptic network of LGS. This network is present early (in children) and late (in older patients) in the course of the syndrome and across diverse etiologies of epilepsy, suggesting that LGS reflects shared "secondary network" involvement. A cortical-to-subcortical hierarchy is postulated whereby GPFA rapidly propagates from prefrontal cortex to the brainstem via extrapyramidal corticoreticular pathways, whereas the thalamus is engaged secondarily.

Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome.

We previously observed that adults with Lennox-Gastaut syndrome (LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging (fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography (EEG) was acquired during presurgical fMRI. Presurgical and postsurgical functional connectivity were compared using (1) graph theoretical analyses of small-world network organization and node-wise strength; and (2) seed-based analyses of connectivity within and between five functional networks. To explore the specificity of these postsurgical network changes, connectivity was further compared to nine children with LGS who did not undergo surgery. The presurgical EEG-fMRI revealed diffuse activation of association cortex during interictal discharges. Following surgery and seizure control, functional connectivity showed increased small-world organization, stronger connectivity in subcortical structures, and greater within-network integration/between-network segregation. These changes suggest network improvement, and diverged sharply from the comparison group of nonoperated children. Following surgery, this child with LGS achieved seizure control and showed extensive reorganization of networks that underpin cognition. This case illustrates that the epileptic process of LGS can directly contribute to abnormal network organization, and that this network disruption may be reversible.

Centre of epileptogenic tubers generate and propagate seizures in tuberous sclerosis.

SEE DUCHOWNY DOI101093/AWW216 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Multiple seizure foci, seizure propagation and epileptic spasms complicate presurgical seizure localization in tuberous sclerosis. Furthermore, controversy exists about the contribution of tubers, perituberal cortex and the underlying genetic abnormality to epileptogenesis. We aimed to determine the epileptogenic substrate in tuberous sclerosis by studying spatio-temporal patterns of seizure onset and propagation on intracranial EEG recordings in which multiple depth and surface electrodes sampled multiple tubers and perituberal cortex. Ten intracranial EEG recordings (seven extraoperative, three intraoperative) from 10 children with tuberous sclerosis were analysed. Notable thickening and signal abnormality in the centre of many tubers on magnetic resonance imaging led to tuber centres being recorded with depth electrodes. Spatially-meaningful bipolar montages were reformatted incorporating channels recording only from the tuber centre, tuber rim and perituberal cortex. Interictal epileptiform discharges and ictal rhythms were analysed visually for location, field, morphology, frequency, latency and temporal dispersion. Fifteen electroclinically distinct seizures were recorded in the 10 patients. Seizure onset was recorded in tubers in all 15 electroclinically distinct seizures; in 9/10 electroclinically distinct seizures recorded with optimal spatial sampling, seizure onset was recorded in the tuber centre, with or without involvement of the tuber rim but not perituberal cortex. Quantitative electroencephalography analysis by pairwise cross-correlation confirmed that the tuber centre led the tuber rim and perituberal cortex during interictal, preictal and ictal spike trains. Seizure propagation was observed in 10/15 electroclinically distinct seizures, being tuber-to-tuber in all. Seven of the 17 tubers showing seizure propagation activated an independent ictal rhythm, morphologically distinct from that seen in seizure onset region (intra-ictal activation). Of the total 48 tubers sampled, 16 exhibited seizure onset, 17 were involved in seizure propagation and 40 exhibited interictal epileptiform discharges, 33 independent and seven propagated. Seizure onsets were recorded in 16/33 tubers with independent interictal epileptiform discharges, but 0/7 tubers with only propagated epileptiform discharges or 0/8 tubers with no epileptiform discharges (P = 0.003). Seizure onsets were recorded from 4/7 tubers with and 0/10 tubers without intra-ictal activation (P = 0.015). Thus, focal seizures and interictal epileptiform discharges in tuberous sclerosis arise in the centre of epileptogenic tubers and propagate to the tuber rim, perituberal cortex and other epileptogenic tubers. Rhythmic interictal epileptiform discharges and intra-ictal activation of propagated ictal rhythms are potential biomarkers of epileptogenic tubers. Interictal and ictal EEG features of epileptogenic tubers have similarities to focal cortical dysplasia type II, consistent with the reported imaging, histological and molecular similarities.

Ictal unilateral blinking is an unreliable lateralizing sign in tuberous sclerosis complex.

OBJECTIVE: Ictal unilateral blinking is an uncommon but reportedly reliable lateralizing sign, indicating an ipsilateral seizure focus. We aimed to determine its lateralizing utility in patients with tuberous sclerosis complex (TSC). METHODS: We reviewed the video-EEGs of 92 children with TSC and drug-resistant epilepsy. Eleven (12%) had seizures with unilateral blinking, of which 10 underwent epilepsy surgery. Lateralization of seizures was inferred from other semiology, ictal scalp EEG and outcome following tuberectomy. RESULTS: Seizures manifesting with unilateral blinking were focal motor in four patients, focal motor evolving into epileptic spasms in six, and epileptic spasms with focal features in one. Associated unilateral facial contraction was seen in five patients and arm jerking in four. Lateralized scalp ictal rhythms were seen in seven patients. Following tuberectomies, seven patients are seizure free and two had >90% reduction. Overall lateralization of seizures with unilateral blinking was contralateral in six patients and ipsilateral in four. When unilateral blinking was early in seizures, overall lateralization was more often contralateral (6/7 patients, PPV 85%). SIGNIFICANCE: Ictal unilateral blinking is not infrequent but unreliable in lateralizing seizures in TSC. Unrecognized seizure propagation to contralateral symptomatogenic regions and potentially different mechanisms may account for the variable lateralization.

Creative writing and dementia care: 'making it real'.

BACKGROUND: Health professionals continue to seek ways to promote positive communication and self-worth when supporting people living with dementia. The value of creative writing techniques as part of reflective practice in nursing and caring for older people with dementia needs further exploration. AIM: To introduce creative writing techniques to health professionals as part of dementia-related reflective practice. METHOD: A local experienced author facilitated creative writing workshops with nine preregistration nursing students (general and mental health), one family carer and five care professionals working with people with dementia. FINDINGS: The student nurses reported that the creative writing exercises felt more 'real' than the reflective practice models they had used in their academic and practical studies. Workshop participants also reported they had learnt some creative writing techniques to reduce work-related stress and anxiety. They also saw the impact of writing activities with people living with dementia, which can enable creativity and 'alleviate the common symptoms of depression and anxiety'. CONCLUSION: Creative writing techniques can support insightful, reflective dementia focused practice. IMPLICATIONS FOR PRACTICE: Creative writing, as a tool in reflective practice, may enable health professionals and family carers to become confident and creative partners in older people's care. The added value, time and investment needed to introduce creative writing need to be articulated and acknowledged from within supervision and staffing teams.