Alzheimer's disease is marked by brain damage from tau and amyloid aggregates, particularly to the hippocampus and the default network. A new study in PLOS Biology shows sex differences in the ...patterns of damage and in their association with risk and protective factors.
Objective
To describe the incidence, risks, management and outcomes of cardiac arrest in pregnancy in the UK population, with specific focus on the use of perimortem caesarean section (PMCS).
Design
...A prospective, descriptive study using the UK Obstetric Surveillance System (UKOSS).
Setting
All UK hospitals with maternity units.
Population
All women who received basic life support in pregnancy in the UK between 1 July 2011 and 30 June 2014 (n = 66).
Methods
Prospective case identification through UKOSS monthly mailing.
Main outcome measures
Cardiac arrest in pregnancy, PMCS, maternal death.
Results
There were 66 cardiac arrests in pregnancy, resulting in an incidence of 2.78 per 100 000 maternities (1:36 000; 95% CI 2.2–3.6). In all, 28 women died (case fatality rate 42%); 16 women arrested solely as a consequence of obstetric anaesthesia, 12 of whom were obese. Basic and advanced life support were rapidly delivered. Those who died were more likely to have collapsed at home. Perimortem caesarean section was performed in 49 women, 11 in the emergency department. The time from collapse to PMCS was significantly shorter in women who survived (median interval 3 versus 12 minutes, P = 0.001). Forty‐six of 58 babies were born alive; 32 babies to surviving mothers and 14 to women who died.
Conclusion
Cardiac arrest is rare in the pregnant UK population, however, nearly a quarter of cases are precipitated by obstetric anaesthesia, suggesting an opportunity to reduce the incidence further. Maternal survival rates of 58% were achieved with timely resuscitation, including PMCS, delay in which was associated with maternal death. Inpatient arrests were associated with higher survival rates than arrests that occurred outside the hospital setting.
Tweetable
25% of cardiac arrest in pregnancy is caused by anaesthesia. Rapid perimortem section improves survival.
Tweetable
25% of cardiac arrest in pregnancy is caused by anaesthesia. Rapid perimortem section improves survival.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights14521.
Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally.
To ...characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures.
A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials.
The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Abeta-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures.
The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.
The Politics of Injustice Beckett, Katherine A; Sasson, Theodore
2003, 2004, 2003-10-16, 20040101
eBook
Examining the role of crime in American politics and culture, The Politics of Injustice, Second Edition provides a better understanding of the nature of crime and punishment in America, as well as ...the cultural and political contexts in which they occur.
The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity ...for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
The Centers for Disease Control and Prevention (CDC) and a group of governmental and private sector partners developed these evidence-based recommendations to increase the proportion of hepatitis C ...virus (HCV)-infected persons who know their status and are linked to appropriate care and treatment. The recommendations also address brief alcohol screening, as alcohol accelerates progression of liver disease among HCV-infected individuals. These recommendations augment CDC's 1998 and 1999 recommendations based on risk and medical indications and are not meant to replace those recommendations.
These recommendations are based on systematic reviews of evidence published from 1995 through February 2012 in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Database of Abstracts of Reviews of Effects. Selected studies included cross-sectional and cohort studies that addressed either prevalence of hepatitis C in the United States or clinical outcomes (for example, hepatocellular carcinoma and serious adverse events) among treated patients and systematic reviews of trials that assessed effectiveness of brief screening interventions for alcohol consumption. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess quality of the evidence. RECOMMENDATION 1: Adults born during 1945-1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: All persons with identified HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Grade: strong recommendation; moderate-quality evidence).
Abstract Introduction The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August ...1, 2016, is a 5-year renewal of the current ADNI-2 study. Methods ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Results Multimodal analyses will provide insight into AD pathophysiology and disease progression. Discussion ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.
Abstract Introduction The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and ...breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. Methods We used standard searches to find publications using ADNI data. Results (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by “classic” AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. Discussion Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial design.
The synthesis and characterization of six new substituted guanidium tetrahydroxidohexaoxidopentaborate(1-) salts are reported: C(NH
)
(NHMe)B
O
(OH)
·H
O (
), C(NH
)
(NH{NH
})B
O
(OH)
(
), C(NH
)
...(NMe
)B
O
(OH)
(
), C(NH
)(NMe
)
B
O
(OH)
(
), C(NHMe)(NMe
)
B
O
(OH)
·B(OH)
(
), and TBDHB
O
(OH)
(
) (TBD = 1,5,7-triazabicyclo 4.4.0dec-5-ene). Compounds
-
were prepared as crystalline salts from basic aqueous solution via self-assembly processes from B(OH)
and the appropriate substituted cation. Compounds
-
were characterized by spectroscopic (NMR and IR) and by single-crystal XRD studies. A thermal (TGA) analysis on compounds
-
and
demonstrated that they thermally decomposed via a multistage process to B
O
at >650 °C. The low temperature stage (<250 °C) was endothermic and corresponded to a loss of H
O. Reactant stoichiometry, solid-state packing, and H-bonding interactions are all important in assembling these structures. An analysis of H-bonding motifs in known unsubstituted guanidinium salts C(NH
)
B
O
(OH)
·2H
O, C(NH
)
B
O
(OH)
·H
O, and C(NH
)
B
O
(OH)
and in compounds
-
revealed that two important H-bonding R
(8) motifs competed to stabilize the observed structures. The guanidinium cation formed charge-assisted pincer cation-anion H-bonded rings as a major motif in C(NH
)
B
O
(OH)
·2H
O and C(NH
)
B
O
(OH)
, whereas the anion-anion ring motif was dominant in C(NH
)
B
O
(OH)
·H
O and in compounds
-
. This behaviour was consistent with the stoichiometry of the salt and packing effects also strongly influencing their solid-state structures.
Patients with Alzheimer’s disease show reduced cerebral blood flow, but it is unclear how this relates to β-amyloid pathology. By comparing patients with Alzheimer’s dementia, mild cognitive ...impairment, and controls, Mattsson et al. show that high β-amyloid load is associated with increased atrophy and reduced perfusion, independent of diagnosis.
Patients with Alzheimer’s disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer’s Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer’s disease with dementia (n = 24). Based on the theory that Alzheimer’s disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-β pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.
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