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Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
The COVID-19 pandemic requires an effort to coordinate the actions of government and society in a way unmatched in recent history. Individual citizens need to voluntarily sacrifice economic and social activity for an indefinite period of time to protect others. At the same time, we know that public opinion tends to become polarized on highly salient issues, except when political elites are in consensus (Berinsky, 2009; Zaller, 1992). Avoiding elite and public polarization is thus essential for an effective societal response to the pandemic. In the United States, there appears to be elite and public polarization on the severity of the pandemic (Gadarian et al., 2020). Other evidence suggests that polarization is undermining compliance with social distancing (Cornelson and Miloucheva, 2020). Using a multimethod approach, we show that Canadian political elites and the public are in a unique period of cross-partisan consensus on important questions related to the COVID-19 pandemic, such as its seriousness and the necessity of social distancing.
The Pennsylvania Longitudinal Study of Parents and Children Twin Registry was developed to capture a representative sample of multiple births and their parents in the state of Pennsylvania. The registry has two main efforts. The first began in 2012 through recruitment of adolescents in Pennsylvania schools. The second effort began in January 2019 in partnership with the Pennsylvania Department of Health to capture the birth cohort of twins born from 2007 to 2017. Study recruitment, sample demographics, focus and measures are provided, as well as future directions.
We report a summary of Portuguese families and siblings research under the umbrella of the Portuguese Healthy Family Project. Families lived in mainland Portugal, as well as in the Azores and Madeira islands. All samples comprise children and adolescents (9–20 years) and their parents (27–57 years). Recruitment procedures and phenotypes were detailed. Familial resemblance in body shape and composition, metabolic syndrome, physical fitness, physical activity and sedentary behaviors are presented, as well as future research avenues.
Sub-Saharan Africa has the highest natural twinning rate in the world. Unfortunately, due to lack of adequate care during pregnancy, labor and postnatally, twin mortality in Sub-Saharan Africa also remains very high. Thus, it has been estimated that one in five twins dies during the childhood years. In spite of this, surprisingly few twin studies have been conducted in the region, making additional epidemiological data much needed. In 2009, we established one of the first twin registries in Sub-Saharan Africa at the Bandim Health Project in Guinea-Bissau. The registry had two main objectives. First, we wanted to describe the twinning rate and mortality patterns among newborn twins, including mortality risk factors and hospitalization patterns. Such studies can help the local clinicians improve twin health by identifying the most vulnerable children. Second, and in light of the rapidly increasing diabetes rates in Africa, we wanted to use the registry to particularly focus on metabolic disorders. Twins are often born with low birth weight, which according to the ‘thrifty phenotype hypothesis’ could predispose them to metabolic disorders later in life. Yet, no such ‘fetal programming’ data have previously been available from African twins despite the fact that nutritional patterns and influences from other factors (e.g., infections) could be markedly different here compared to high-income settings. In this article, we summarize the findings and current status of the Guinea-Bissau twin registry.
Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of −1.11 (95% credible interval −1.62 to −0.60) for face-to-face CBT, −1.06 (−2.05 to −0.08) for hybrid CBT, and −0.59 (−1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible.
The 1983 case Racine v Woods is the leading child protection case from the Supreme Court of Canada, distinguishing bonding and/or attachment as a more important determinant of best interest for an Indigenous child than cultural connection. Using this case, courts are upholding the permanent placement of Indigenous children in non-Indigenous homes as opposed to placement within their culture. Racine v Woods reflected knowledge of attachment and family at that time but runs counter to current knowledge. Reconsideration of the factors to decide cross-cultural adoption is needed. The essential point is that attachment assessment draws from a dyadic relational theory and is being applied to communal family systems, such as Indigenous systems. Such a review is consistent with the calls to action of the Truth and Reconciliation Commission (TRC) as well as its predecessor, the Royal Commission on Aboriginal Peoples (RCAP), and recent Canadian Human Rights Tribunal (CHRT) decisions.
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
Holt et al show that a lifestyle intervention did not reduce weight in people with schizophrenia. The STEPWISE trial casts a critical focus on the challenges of improving physical health in people with schizophrenia. The trial underpins efforts to maintain momentum in overcoming the unacceptable health inequalities in this population.
Modern welfare regimes rest on a range of actors – state, market, family/households, employers and charities – but austerity programmes diminish the contribution of the state. While changes in this ‘welfare mix’ require support from the population, attitude studies have focused mainly on people’s views on state responsibilities, using welfare regime theory to explain differences. This paper contributes to our understanding of the welfare mix by including other providers such as the market, the family or employers, and also introduces social risk theories, contrasting new and old risks. Regime theory implies differences will persist over time, but risk theory suggests that growing similarities in certain risks may tend to promote international convergence. This article examines attitudes to the roles of state, market, family, charity/community and employer for pension and childcare in Germany and the UK. We collected data using deliberative forums, a new method in social policy research that allows citizens space to pursue extended lightly moderated discussion and permits researchers to analyse people’s justifications for their attitudes. Our research indicated patterns of convergence especially in preferences for childcare, but that regime predominates in people’s justifications for their attitudes: regime differences in attitudes are resilient.
Type 2 diabetes mellitus (T2DM) is a global public health epidemic. Diet and lifestyle changes have been demonstrated as effective measures in managing T2DM and preventing or delaying the progression from prediabetes to diabetes, yet the relationship between diet, prediabetes and diabetes is still not entirely clear. The present study aimed to further elucidate the relationship between diet, diabetes and especially prediabetes. A total of 1542 participants of the cross-sectional, population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013/2014) were included in this analysis. Dietary intake was derived using a method combining information from a FFQ and repeated 24-h food lists. Glucose tolerance status was assessed via oral glucose tolerance tests in all participants without a previous physician-confirmed diagnosis of T2DM, and was classified according to the 2003 American Diabetes Association criteria. Crude and fully adjusted multinomial logistic regression models were fitted to examine associations between diet and prediabetes, undetected diabetes mellitus (UDM) and prevalent T2DM. After adjusting for major covariates, fruit was significantly inversely and total meat, processed meat, sugar-sweetened beverages and moderate alcohol significantly associated with UDM and/or prevalent diabetes. Sex-specific analyses showed that in men, coffee was significantly inversely (OR 0·80; 95 % CI 0·67, 0·96) and heavy alcohol significantly (OR 1·84; 95 % CI 1·14, 2·95) associated with prediabetes. Our findings on diet and T2DM are consistent with current literature, while our results regarding coffee, heavy alcohol consumption and prediabetes highlight new possible targets for primary prevention of the derangement of glucose homeostasis.
In their 1960 book on finite Markov chains, Kemeny and Snell established that a certain sum is invariant. The value of this sum has become known as Kemeny’s constant. Various proofs have been given over time, some more technical than others. We give here a very simple physical justification, which extends without a hitch to continuous-time Markov chains on a finite state space. For Markov chains with denumerably infinite state space, the constant may be infinite and even if it is finite, there is no guarantee that the physical argument will hold. We show that the physical interpretation does go through for the special case of a birth-and-death process with a finite value of Kemeny’s constant.
Fertility is one of the most economically important traits in both beef and dairy cattle production; however, only female fertility is typically subjected to selection. Male and female fertility have only a small positive genetic correlation which is likely due to the existence of a relatively small number of genetic variants within each breed that cause embryonic and developmental losses. Genomic tools have been developed that allow the identification of lethal recessive loci based upon marker haplotypes. Selection against haplotypes harbouring lethal alleles in conjunction with selection to improve female fertility will result in an improvement in male fertility. Genomic selection has resulted in a two to fourfold increase in the rate of genetic improvement of most dairy traits in US Holstein cattle, including female fertility. Considering the rapidly increasing rate of adoption of high-throughput single nucleotide polymorphism genotyping in both the US dairy and beef industries, genomic selection should be the most effective of all currently available approaches to improve male fertility. However, male fertility phenotypes are not routinely recorded in natural service mating systems and when artificial insemination is used, semen doses may be titrated to lower post-thaw progressively motile sperm numbers for high-merit and high-demand bulls. Standardization of sperm dosages across bull studs for semen distributed from young bulls would allow the capture of sire conception rate phenotypes for young bulls that could be used to generate predictions of genetic merit for male fertility in both males and females. These data would allow genomic selection to be implemented for male fertility in addition to female fertility within the US dairy industry. While the rate of use of artificial insemination is much lower within the US beef industry, the adoption of sexed semen in the dairy industry has allowed dairy herds to select cows from which heifer replacements are produced and cows that are used to produce terminal crossbred bull calves sired by beef breed bulls. Capture of sire conception rate phenotypes in dairy herds utilizing sexed semen will contribute data enabling genomic selection for male fertility in beef cattle breeds. As the commercial sector of the beef industry increasingly adopts fixed-time artificial insemination, sire conception rate phenotypes can be captured to facilitate the development of estimates of genetic merit for male fertility within US beef breeds.
Examining neurometabolic abnormalities in critical brain areas in schizophrenia and major depressive disorder (MDD) may help guide future pharmacological interventions including glutamate-modulating treatments.
To measure metabolite concentrations within the anterior cingulate cortex (ACC) and thalamus of people with schizophrenia and people with MDD.
Spectra were acquired from 16 volunteers with schizophrenia, 17 with MDD and 18 healthy controls using magnetic resonance spectroscopy on a 7 Tesla scanner.
In the thalamus, there were lower glycine concentrations in the schizophrenia group relative to control (P=0.017) and MDD groups (P=0.012), and higher glutamine concentrations relative to healthy controls (P=0.009). In the thalamus and the ACC, the MDD group had lower myo-inositol concentrations than the control (P=0.014, P=0.009, respectively) and schizophrenia (P=0.004, P=0.002, respectively) groups.
These results support the glutamatergic theory of schizophrenia and indicate a potential glycine deficiency in the thalamus. In addition, reduced myo-inositol concentrations in MDD suggest its involvement in the disorder.
The double crisis approach distinguishes two kinds of challenge confronting modern welfare states: long-term structural problems and short-term difficulties resulting from policy choices which affect the success with which the long-term issues can be addressed. Structural challenges include two main areas:
• globalisation and technological changes demanding that governments direct attention to national competitiveness, and
• population ageing, requiring more spending on pensions, and health and social care.
Recent policy-related problems include the austerity programme since 2010 which has been particularly directed towards benefits and services for working-age people. Responses to both kinds of challenge have set the stage for Brexit.
The aim of this article is to investigate the argument that choice and competition will unleash entrepreneurial innovation in free schools. Free schools were introduced as a subset of the Academies by the Conservative–Liberal Democrat Coalition government, following the general election in 2010. The government made it possible for non-state providers to set up their own independent, state-funded schools in order to create more choice, competition and innovation. We conclude that a higher level of substantive innovation is taking place in regards to management practices than in respect of curriculum and pedagogical practices. Innovation in curriculum and pedagogical practices is very limited. Creating a free school offer that seems to differ from other schools appears to be done through marketing and branding rather than innovation. We argue that parents, OFSTED, and the relative isolation of free schools constrain innovation from taking place.
Over 1 billion children worldwide are exposed to political violence and armed conflict. The current conclusions are qualified by limited longitudinal research testing sophisticated process-oriented explanatory models for child adjustment outcomes. In this study, consistent with a developmental psychopathology perspective emphasizing the value of process-oriented longitudinal study of child adjustment in developmental and social–ecological contexts, we tested emotional insecurity about the community as a dynamic, within-person mediating process for relations between sectarian community violence and child adjustment. Specifically, this study explored children's emotional insecurity at a person-oriented level of analysis assessed over 5 consecutive years, with child gender examined as a moderator of indirect effects between sectarian community violence and child adjustment. In the context of a five-wave longitudinal research design, participants included 928 mother–child dyads in Belfast (453 boys, 475 girls) drawn from socially deprived, ethnically homogenous areas that had experienced political violence. Youth ranged in age from 10 to 20 years and were 13.24 (SD = 1.83) years old on average at the initial time point. Greater insecurity about the community measured over multiple time points mediated relations between sectarian community violence and youth's total adjustment problems. The pathway from sectarian community violence to emotional insecurity about the community was moderated by child gender, with relations to emotional insecurity about the community stronger for girls than for boys. The results suggest that ameliorating children's insecurity about community in contexts of political violence is an important goal toward improving adolescents' well-being and adjustment. These results are discussed in terms of their translational research implications, consistent with a developmental psychopathology model for the interface between basic and intervention research.
Improving children's learning and development in conflict-affected countries is critically important for breaking the intergenerational transmission of violence and poverty. Yet there is currently a stunning lack of rigorous evidence as to whether and how programs to improve learning and development in conflict-affected countries actually work to bolster children's academic learning and socioemotional development. This study tests a theory of change derived from the fields of developmental psychopathology and social ecology about how a school-based universal socioemotional learning program, the International Rescue Committee's Learning to Read in a Healing Classroom (LRHC), impacts children's learning and development. The study was implemented in three conflict-affected provinces of the Democratic Republic of the Congo and employed a cluster-randomized waitlist control design to estimate impact. Using multilevel structural equation modeling techniques, we found support for the central pathways in the LRHC theory of change. Specifically, we found that LRHC differentially impacted dimensions of the quality of the school and classroom environment at the end of the first year of the intervention, and that in turn these dimensions of quality were differentially associated with child academic and socioemotional outcomes. Future implications and directions are discussed.