To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8–6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Māori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.
Objectives: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer’s disease (AD) and other neurological disorders, including Huntington’s disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. Methods: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes – across-trial novel intrusions and across/within trial repeated intrusions – in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. Results: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. Conclusions: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
Traditionally, design opportunities and directions are conceived based on expertise, intuition, or time-consuming user studies and marketing research at the fuzzy front end of the design process. Herein, we propose the use of the total technology space map (TSM) as a visual ideation aid for rapidly conceiving high-level design opportunities. The map is comprised of various technology domains positioned according to knowledge proximity, which is measured based on a large quantity of patent data. It provides a systematic picture of the total technology space to enable stimulated ideation beyond the designer's knowledge. Designers can browse the map and navigate various technologies to conceive new design opportunities that relate different technologies across the space. We demonstrate the process of using TSM as a rapid ideation aid and then analyze its applications in two experiments to show its effectiveness and limitations. Furthermore, we have developed a cloud-based system for computer-aided ideation, that is, InnoGPS, to integrate interactive map browsing for conceiving high-level design opportunities with domain-specific patent retrieval for stimulating concrete technical concepts, and to potentially embed machine-learning and artificial intelligence in the map-aided ideation process.
Objectives: Although subjective cognitive complaints (SCC) are an integral component of the diagnostic criteria for mild cognitive impairment (MCI), previous findings indicate they may not accurately reflect cognitive ability. Within the Alzheimer’s Disease Neuroimaging Initiative, we investigated longitudinal change in the discrepancy between self- and informant-reported SCC across empirically derived subtypes of MCI and normal control (NC) participants. Methods: Data were obtained for 353 MCI participants and 122 “robust” NC participants. Participants were classified into three subtypes at baseline via cluster analysis: amnestic MCI, mixed MCI, and cluster-derived normal (CDN), a presumptive false-positive group who performed within normal limits on neuropsychological testing. SCC at baseline and two annual follow-up visits were assessed via the Everyday Cognition Questionnaire (ECog), and discrepancy scores between self- and informant-report were calculated. Analysis of change was conducted using analysis of covariance. Results: The amnestic and mixed MCI subtypes demonstrated increasing ECog discrepancy scores over time. This was driven by an increase in informant-reported SCC, which corresponded to participants’ objective cognitive decline, despite stable self-reported SCC. Increasing unawareness was associated with cerebrospinal fluid Alzheimer’s disease biomarker positivity and progression to Alzheimer’s disease. In contrast, CDN and NC groups over-reported cognitive difficulty and demonstrated normal cognition at all time points. Conclusions: MCI participants’ discrepancy scores indicate progressive underappreciation of their evolving cognitive deficits. Consistent over-reporting in the CDN and NC groups despite normal objective cognition suggests that self-reported SCC do not predict impending cognitive decline. Results demonstrate that self-reported SCC become increasingly misleading as objective cognitive impairment becomes more pronounced. (JINS, 2018, 24, 842–853)
Objectives: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington’s disease [HD]). Methods: We compared the performance of individuals with Alzheimer’s disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Results: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Conclusions: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833–841)
Objectives: Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. Methods: A total of 806 participants diagnosed by means of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on “robust” normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Results: Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer’s disease CSF biomarkers than LPA-derived normal subjects. Conclusions: Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent “false-positive” diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564–576)
Objectives: Within the Alzheimer’s Disease Neuroimaging Initiative (ADNI)’s mild cognitive impairment (MCI) cohort, we previously identified MCI subtypes as well as participants initially diagnosed with MCI but found to have normal neuropsychological, biomarker, and neuroimaging profiles. We investigated the functional change over time in these empirically derived MCI subgroups. Methods: ADNI MCI participants (n=654) were classified using cluster analysis as Amnestic MCI (single-domain memory impairment), Dysnomic MCI (memory+language impairments), Dysexecutive/Mixed MCI (memory+language+attention/executive impairments), or Cluster-Derived Normal (CDN). Robust normal control participants (NCs; n=284) were also examined. The Functional Activities Questionnaire (FAQ) was administered at baseline through 48-month follow-up. Multilevel modeling examined FAQ trajectories by cognitive subgroup. Results: The Dysexecutive/Mixed group demonstrated the fastest rate of decline across all groups. Amnestic and Dysnomic groups showed steeper rates of decline than CDNs. While CDNs had more functional difficulty than NCs across visits, both groups’ mean FAQ scores remained below its suggested cutoff at all visits. Conclusions: Results (a) show the importance of executive dysfunction in the context of other impaired cognitive domains when predicting functional decline in at-risk elders, and (b) support our previous work demonstrating that ADNI’s MCI criteria may have resulted in false-positive MCI diagnoses, given the CDN’s better FAQ trajectory than those of the cognitively impaired MCI groups. (JINS, 2017, 23, 521–527)
One of the most notable currents in social, cultural and political historiography is the interrogation of the categories of 'elite' and 'popular' politics and their relationship to each other, as wellas the exploration of why and how different sorts of people engaged with politics and behaved politically. While such issues are timeless, they hold a special importance for a society experiencing rapid political and social change, like early modern England. No one has done more to define these agendas for early modern historians than John Walter. His work has been hugely influential, and at itsheart has been the analysis of the political agency of ordinary people. The essays in this volume engage with the central issues of Walter's work, ranging across the politics of poverty, dearth and household, popular political consciousness and practice more broadly, and religion and politics during the English revolution. This outstanding collection, bringing together some of the leading historians of this period with some of the field's rising stars, will appeal to anyone interested in the social, cultural and political history of early modern England or issues of popular political consciousness and behaviour more generally.
MICHAEL J. BRADDICK is professor of history at the University of Sheffield. PHIL WITHINGTON is professor of history at the University of Sheffield.
CONTRIBUTORS: Michael J. Braddick, J. C. Davis, Amanda Flather, Steve Hindle, Mark Knights, John Morrill, Alexandra Shepard, Paul Slack, Richard M. Smith, Clodagh Tait, Keith Thomas, Phil Withington, Andy Wood, Keith Wrightson.
In 1642, Anne Read's husband died of grief. In the same year, Sir Con Magennis died tormented by his evil deeds and ‘much … affrighted with the apprehension and conceipt that … Mr Tudge [a minister he had slain] was still in his presence’.Early modern people attributed huge consequence to ‘passions’ (they would not have used the word ‘emotion’) like grief, anger and fear. When uncontrolled, ‘passion’ started wars and ended life. Little wonder that contemporaries urged the restraint of potentially damaging feelings. However, there were times when emotions were particularly difficult to check.
John Walter's recent work on the collection of documents called the 1641 Depositions has assisted in building a new understanding of the outbreak of waves of violence in Ireland in 1641–2 and subsequently. The depositions contain testimonies from about 3,000 people, mostly British Protestant settlers, who had been dispossessed of their lands, homes and goods by Catholic rebels. Some had been confronted by crowds of local people, though as the rebellion continued, gentlemen tended to take over the leadership of these attacks. Either way, most of the deponents could identify at least some of those involved. The majority had been threatened with violence, and many bore tales of loss of property, personal injury and the torture and violent deaths of their family members, friends and neighbours. There were also accounts of incidents of desecration of sacred space and iconoclasm and of the deliberate humiliation of victims, who were routinely stripped and insulted. The depositions also contain a later set of ‘examinations’, usually conducted to probe particular crimes that had occurred in the early 1640s. The testimonies here included those of both settler and native witnesses and alleged perpetrators. It is no surprise, therefore, that Nicholas Canny should have described the depositions as ‘a body of material which is emotional’. Historians of the period often reflect on the emotional state of the Gaelic Irish and Old English participants, to paint a picture of simmering humiliation, shame, resentment, hostility, fear, hatred, anxiety and despair that led to outpourings of vengeful rage. Though economic and other grievances are pinpointed as arousing these emotions, they are regularly fathered above all on religion: Inga Jones argues that ‘religion has the capacity to arouse passions which go beyond what political and localist concerns can stimulate, a passion which … could and did spill over into unrestrained slaughter’.