We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save 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 saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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 have previously argued thatbehavioral scientists have been testing and advocating individualistic (i-frame) solutions to policy problems that have systemic (s-frame) causes and require systemic solutions. Here, we consider the implications of adopting an s-frame approach for research. We argue that an s-frame approach will involve addressing different types of questions, which will, in turn, require a different toolbox of research methods.
Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.
Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.
Table for P.120
Patients
Age/Sex
Development
Age of
seizure onset
Epilepsy type
Current antiseizure medication
Seizure frequency
Gene variant/Function
Inheritance
P1
14y/F
Profound GDD
5m
Infantile spasms, LGS, hyperkinetic movements
Clobazam
Daily
c.1238C>A (p.Ala413Asp)
De novo
P2
6y/F
Normal
3-7m
Focal epilepsy
Carbamazepine
Seizure free
c.5630A>G (p.Asn1877Ser)/GoF
Paternal
P3
4y/F
Normal
12m
Focal epilepsy
Clobazam, topiramate
Seizure free
c.4447G>A (p.Glu1483Lys)
De novo
P4
6y/F
GDD, autism
3y - EEG abnormality only
-
Sodium valproate (discontinued)
No clinical seizure
c.971G>A (p.Cys324Tyr)/LoF, VUS in KCNQ3
De novo
P5
7y/M
GDD
5m
Generalized seizures
Ethosuximide, acetazolamide
Daily
c.773C>T (p.Thr258Ile)
De novo
P6
19y/F
Normal
10y
Focal epilepsy
Carbamazepine
Seizure free
c.986A>G (p.Asp329Gly)
De novo
Abbreviations: *Father with similar history, y Years, m Months, GDD Global developmental delay, LGS Lennox-Gastaut syndrome, VUS Variant of unknown significance, LoF Loss-of-function, GoF Gain-of-function, EEG Electroencephalogram, F - Female, M - Male, CBD - Cannabidiol
This article provides the first systematic interpretation of the moral theory developed in Newcome's Enquiry into the Evidence of the Christian Religion (1728, revised 1732). More importantly, it shows that Newcome's views constitute a valuable but overlooked contribution to the development of utilitarianism. Indeed, she is arguably the first utilitarian. Her ethical views are considered in two stages. The article first explores her hedonist approach to the good and then turns to her consequentialist account of right action. The article then situates Newcome's work within the context of the pre-Bentham utilitarian movement. Strikingly, Newcome lived and worked in close proximity to other prominent early utilitarians and was well positioned to have exerted an influence on the development of their views. Newcome has never been discussed in connection with the history of ethics. This article constitutes an argument for her inclusion in our narratives about the development of a major moral theory.
This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.
Unaffected healthy 1st degree relatives of patients with major depressive disorder (MDD) are 3.6 times more liable to develop the disease themselves than the standard population without the history of the disorder. Neural correlates of this liability are of particular interest since the phenomenon does not always have behavioral manifestations and early detected can enhance quicker and better MDD prevention.
Objective
The objective of our study was to establish neuronal correlates of susceptibility MDD in unaffected healthy 1st degree relatives of patients with MDD. Inhibition of emotional information was examined in the present study.
Aims
The aim of the study was to better understand the development of MDD and the role of altered inhibition of emotional processing in it. That, in consequence, may contribute to establishing new methods of prevention and quicker detection of MDD liability.
Methods
Twenty-one unaffected healthy 1st degree relatives of patients with MDD and twenty-five matched healthy controls underwent a functional magnetic resonance imaging procedure with a task involving inhibition of emotional processing of positive, negative and neutral emotional information. 2 × 3 ANOVA was performed to establish if the two groups differed significantly in the inhibition of one of the three types of emotions.
Results
The unaffected healthy 1st degree relatives displayed an increased neural activation during the inhibition of negative emotional information in the bilateral middle cingulate cortex (MCC) and the left caudate nucleus (p< 0.05, family wise error).
Conclusions
The overactivation of the MCC and caudate nucleus can be a marker of MDD liability
The number of older people choosing to relocate to retirement villages (RVs) is increasing rapidly. This choice is often a way to decrease social isolation while still living independently. Loneliness is a significant health issue and contributes to overall frailty, yet RV resident loneliness is poorly understood. Our aim is to describe the prevalence of loneliness and associated factors in a New Zealand RV population.
Design:
A resident survey was used to collect demographics, social engagement, loneliness, and function, as well as a comprehensive geriatric assessment (international Resident Assessment Instrument [interRAI]) as part of the “Older People in Retirement Villages Study.”
Setting:
RVs, Auckland, New Zealand.
Participants:
Participants included RV residents living in 33 RVs (n = 578).
Measurements:
Two types of recruitment: randomly sampled cohort (n = 217) and volunteer sample (n = 361). Independently associated factors for loneliness were determined through multiple logistic regression with odds ratios (ORs).
Results:
Of the participants, 420 (72.7%) were female, 353 (61.1%) lived alone, with the mean age of 81.3 years. InterRAI assessment loneliness (yes/no question) was 25.8% (n = 149), and the resident survey found that 37.4% (n = 216) feel lonely sometimes/often/always. Factors independently associated with interRAI loneliness included being widowed (adjusted OR 8.27; 95% confidence interval [CI] 4.15–16.48), being divorced/separated/never married (OR 4.76; 95% CI 2.15–10.54), poor/fair quality of life (OR 3.37; 95% CI 1.43–7.94), moving to an RV to gain more social connections (OR 1.55; 95% CI 0.99–2.43), and depression risk (medium risk: OR 2.58, 95% CI 1.53–4.35; high risk: OR 4.20, 95% CI 1.47–11.95).
Conclusion:
A considerable proportion of older people living in RVs reported feelings of loneliness, particularly those who were without partners, at risk of depression and decreased quality of life and those who had moved into RVs to increase social connections. Early identification of factors for loneliness in RV residents could support interventions to improve quality of life and positively impact RV resident health and well-being.
Poor physical health in severe mental illness (SMI) remains a major issue for clinical practice.
Aims
To use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder.
Method
We linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data.
Results
There was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high.
Conclusions
Electronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy.
Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Methods
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
Results
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Conclusions
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Cougar Mountain Cave is located in Oregon's Fort Rock Basin. In 1958, avocationalist John Cowles excavated most of the cave's deposits and recovered abundant fiber, lithic, wood, and osseous artifacts. A crew from the University of California, Davis returned to the site in 1966 to evaluate the potential for further research, collecting additional lithic and fiber artifacts from disturbed deposits and in situ charcoal from apparently undisturbed deposits. Because Cowles took few notes or photographs, the Cougar Mountain Cave collection—most of which is housed at the Favell Museum in Klamath Falls, Oregon—has largely gone unstudied even though it contains diagnostic artifacts spanning the Holocene and, potentially, the terminal Pleistocene. We recently submitted charcoal and basketry from the site for radiocarbon dating, providing the first reliable sense of when Cougar Mountain Cave was first occupied. Our results indicate at least a Younger Dryas age for initial occupation. The directly dated basketry has provided new information about the age ranges and spatial distributions of diagnostic textile types in the northwestern Great Basin.