Pathogenic CACNA1A mutations can result in paroxysmal attacks of encephalopathy, hemiplegia and cerebral edema. We report two patients with CACNA1A-associated encephalopathy, hemiplegia and contralateral hemispheric cerebral edema treated successfully with intravenous magnesium sulfate and dexamethasone. One patient met the clinical criteria for familial hemiplegic migraine. There is a paucity of guidance in the literature on how to manage these patients. Despite some discrepancies in the treatment protocols in our two cases, they indicate that magnesium and dexamethasone could be part of the treatment algorithm for these patients. Further research to delineate appropriate dosing and duration of therapy is needed.

EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.

Glass bangles are found in southern England and Wales from the mid-first century ad and become common in the north of England and southern Scotland in the late first century, before their numbers decline a century later. British bangles develop at a time of change, as Roman glassmaking practices were introduced across large areas of Britain, and as blown, transparent, colourless and naturally-coloured glassware became increasingly popular. In many communities, however, there was still a demand for strongly coloured opaque glass, including for bangles, and glassworkers devised ways of extending their supplies of opaque coloured glass. This study is based on over one hundred and fifty analyses of bangle fragments from sites in Wales, northern England and southern Scotland, spanning this transitional period. The bangle makers recycled coloured glass from imported vessels, and probably beads and bangle-making waste, to supplement supplies of fresh coloured glass. The novel methods used to modify and extend the coloured glass may derive from pre-Roman bead-making industries, and made use of widely available materials, including smithing hammerscale and possibly plant ashes. The results show the shifting balance of indigenous and Roman influences on different bangle types, depending on when and where they were made, and by whom.

New Zealand has a strategy of eliminating SARS-CoV-2 that has resulted in a low incidence of reported coronavirus-19 disease (COVID-19). The aim of this study was to describe the spread of SARS-CoV-2 in New Zealand via a nationwide serosurvey of blood donors. Samples (n = 9806) were collected over a month-long period (3 December 2020–6 January 2021) from donors aged 16–88 years. The sample population was geographically spread, covering 16 of 20 district health board regions. A series of Spike-based immunoassays were utilised, and the serological testing algorithm was optimised for specificity given New Zealand is a low prevalence setting. Eighteen samples were seropositive for SARS-CoV-2 antibodies, six of which were retrospectively matched to previously confirmed COVID-19 cases. A further four were from donors that travelled to settings with a high risk of SARS-CoV-2 exposure, suggesting likely infection outside New Zealand. The remaining eight seropositive samples were from seven different district health regions for a true seroprevalence estimate, adjusted for test sensitivity and specificity, of 0.103% (95% confidence interval, 0.09–0.12%). The very low seroprevalence is consistent with limited undetected community transmission and provides robust, serological evidence to support New Zealand's successful elimination strategy for COVID-19.

‘Dementia-friendly communities’ herald a shift toward the neighbourhood as a locus for the care and support of people with dementia, sparking growing interest in the geographies of dementia care and raising questions over the shifting spatial and social experience of the condition. Existing research claims that many people with dementia experience a ‘shrinking world’ whereby the boundaries to their social and physical worlds gradually constrict over time, leading to a loss of control and independence. This paper reports a five-year, international study that investigated the neighbourhood experience of people with dementia and those who care for and support them. We interrogate the notion of a shrinking world and in so doing highlight an absence of attention paid to the agency and actions of people with dementia themselves. The paper draws together a socio-relational and embodied-material approach to question the adequacy of the shrinking world concept as an explanatory framework and to challenge reliance within policy and practice upon notions of place as fixed or stable. We argue instead for the importance of foregrounding ‘lived place’ and attending to social practices and the networks in which such practices evolve. Our findings have implications for policy and practice, emphasising the need to bolster the agency of people living with dementia as a route to fostering accessible and inclusive neighbourhoods.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.

Funding: None

Disclosures: None

Background: Extended-spectrum β-lactamase–producing (ESBL) Escherichia coli infection incidence is increasing in the United States. This increase may be due to the rapid expansion of ST131, which is now the predominant ESBL strain globally, often multidrug resistant, and has been shown to establish longer-term human colonization than other E. coli strains. We assessed potential risk factors that distinguish ST131 from other ESBL E. coli. Methods: From October 1 through December 31, 2017, 5 CDC Emerging Infections Program (EIP) sites pilot tested active, laboratory-based surveillance in selected counties in Colorado, Georgia, New Mexico, New York, and Tennessee. An E. coli case was defined as the first isolation from a normally sterile body site or urine in a surveillance area resident in a 30-day period resistant to 1 extended-spectrum cephalosporin antibiotic and susceptible or intermediate to all carbapenem antibiotics tested. Epidemiologic data were collected from case patients’ medical records. A convenience sample of 117 E. coli isolates from case patients was collected. All isolates underwent whole-genome sequencing to determine sequence type and the presence of ESBL genes. We compared ST131 E. coli epidemiology to other ESBL E. coli. Results: Among 117 E. coli isolates, 97 (83%) were ESBL producers. Of the 97 ESBL E. coli, 52 (54%) were ST131 (range, for 4 EIP sites submitting >10 isolates: 25%–88%; P < .001). Other common STs were ST38 (12%) and ST10 (5%). ST131 infections were more likely to be healthcare-associated than non-ST131 (56% vs 36%; P = .05) (Table 1). Among specific prior healthcare exposures, only residence in long-term care facilities (LTCFs) in the year before culture was more common among ST131 case patients (29% vs 11%; P = .03). Notably, 85% of ESBL E. coli collected from LTCF residents were ST131. ST131 E. coli were more common among patients with underlying medical conditions (81% vs 60%; P = .02). No statistically significant difference by sex, race, age, culture source, location of culture collection, and frequency of antibiotic use in the prior 30 days was observed. Conclusions:The prevalence of ST131 E. coli varies regionally. The association between ST131 and LTCFs suggests that these may be particularly important settings for ST131 acquisition. Improving infection control measures that limit ESBL transmission in these settings and preventing dissemination in facilities receiving patients from LTCFs may be necessary to contain ST131 spread.

Funding: None

Disclosures: None

Background: Hospital-acquired influenza (HA flu) lacks a consensus definition. However, it is known to be associated with increased inpatient morbidity and mortality. Objective: To describe the clinical course of HA flu in a cohort population. Methods: A retrospective cohort study was conducted at a tertiary-care adult and pediatric teaching hospital. Patients with HA flu during 3 seasons, 2016 through 2019, were identified from medical record information based on timing of the onset of signs and symptoms and positive virologic testing >72 hours after admission. Influenza infection was confirmed by multiplex respiratory PCR, influenza A/B PCR, or direct fluorescent antibody tests. Chart review was performed to abstract patient demographics and comorbidities, length of stay, testing, and timing to antiviral administration as well as diagnosis of pneumonia, coinfections, and 30-day mortality. Escalation of care during hospitalization was defined as a new requirement of supplemental oxygen, invasive or noninvasive ventilation, and transfer to an intensive care unit. Results: During the 3 flu seasons, 132 patients were identified with HA flu; 76 (58%) were women, 6 (4.6%) were aged <18 years, and 126 (95.4%) were adults. Annually, HA-flu patients accounted for 5%–7.8% of all patients hospitalized with laboratory-proven influenza. The median duration between hospitalization and positive flu test was 15 days, and the median length of stay after influenza diagnosis was 6 days. Antiviral treatment was received by 96% of the patients. In total, 41 patients (31%) showed radiographic evidence for pneumonia. Coinfection with either a viral or bacterial pathogen was identified in 25% of the cases. In addition, 26% of the patients experienced an escalation of care, and 20 patients (15%) were transferred to the intensive care unit after HA flu diagnosis. Furthermore, 4 deaths (3%) were attributed to influenza during their hospitalization. Conclusions: HA flu was a frequent cause for escalation in care and was associated with a mortality rate substantially higher than is typically seen in community-based populations with influenza. Coinfection was mostly related to bacteremia and pneumonia, yet not all pneumonias had an associated microbiological diagnosis other than influenza, and there was no significant association between coinfection and mortality. Future work should explore more precise definitions for HA flu as well as its complications.

Funding: None

Disclosures: None

The extent of social isolation experienced by people living with dementia who reside in the community has been well acknowledged, yet little is known about how people living alone with dementia maintain neighbourhood-based connections. The purpose of this study is to examine the experiences of people with dementia who live alone, focusing upon how they establish social networks and relationships in a neighbourhood context, and how they are supported to maintain this social context within everyday life. Multiple data collection methods were used including, semi-structured interviews, walking interviews, guided home tours and social network mapping, which were conducted with 14 community-dwelling people living alone with dementia (11 women and three men) situated across the three international study sites in England, Scotland and Sweden. Data were analysed using thematic analysis. The analysis revealed four main themes: (a) making the effort to stay connected; (b) befriending by organisations and facilitated friendships; (c) the quiet neighbourhood atmosphere; and (d) changing social connections. The analysis suggests that people with dementia who live alone were active agents who took control to find and maintain relationships and social networks in the neighbourhood. Our findings indicate the need to raise awareness about this specific group in both policy and practice, and to find creative ways to help people connect through everyday activities and by spontaneous encounters in the neighbourhood.

One of the foundations of product design is the division between production and design. This division manifests as designers aspiring to create fixed iconic archetypes and production replicates endlessly in thousands or millions. Today innovation and technological change are challenging this idea of product design and manufacturing. The evolution of Rapid Prototyping into Additive Manufacturing (AM), is challenging the notion of mass manufacture and consumer value. As AM advances in capability and capacity, the ability to economically manufacture products in low numbers with high degrees of personalisation poses questions of the accepted product development process. Removing the need for dedicated expensive tooling also eliminates the cyclical timescales and commitment to fixed designs that investment in tooling demands. The ability to alter designs arbitrarily, frequently and responsively means that the traditional design process need not be applied and because of this, design processes and practice might be radically different in the future. In this paper, we explore this possible evolution by drawing parallels with principles and development models found in software development.

Since 1975 Richard had been based in Australia, where he taught at the Sydney Conservatorium, but he was born in England, in Chichester, and studied at Hull University. In the late 60s and early 70s he was active as a contemporary music pianist and in the mid-70s became part of the Cologne music scene, working as Stockhausen's Teaching Assistant at the Cologne Staatliche Musikhochschule from 1973 until his move to Australia. But his most significant contribution to new music was as a writer. His 1999 book on the life and work of Ligeti is a superb introduction to the composer's work, and in 2005 it was followed by his book of lectures on Stockhausen, Six Lectures from the Stockhausen Courses Kürten 2002; he also co-edited the collected writings of Ferneyhough with James Boros.