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Oral rotavirus vaccine efficacy estimates from randomised controlled trials are highly variable across settings. Although the randomised study design increases the likelihood of internal validity of findings, results from trials may not always apply outside the context of the study due to differences between trial participants and the target population. Here, we used a weight-based method to transport results from a monovalent rotavirus vaccine clinical trial conducted in Malawi between 2005 and 2008 to a target population of all trial-eligible children in Malawi, represented by data from the 2015–2016 Malawi Demographic and Health Survey (DHS). We reweighted trial participants to reflect the population characteristics described by the Malawi DHS. Vaccine efficacy was estimated for 1008 trial participants after applying these weights such that they represented trial-eligible children in Malawi. We also conducted subgroup analyses to examine the heterogeneous treatment effects by stunting and tuberculosis vaccination status at enrolment. In the original trial, the estimates of one-year vaccine efficacy against severe rotavirus gastroenteritis and any-severity rotavirus gastroenteritis in Malawi were 49.2% (95% CI 15.6%–70.3%) and 32.1% (95% CI 2.5%–53.1%), respectively. After weighting trial participants to represent all trial-eligible children in Malawi, vaccine efficacy increased to 62.2% (95% CI 35.5%–79.0%) against severe rotavirus gastroenteritis and 38.9% (95% CI 11.4%–58.5%) against any-severity rotavirus gastroenteritis. Rotavirus vaccine efficacy may differ between trial participants and target populations when these two populations differ. Differences in tuberculosis vaccination status between the trial sample and DHS population contributed to varying trial and target population vaccine efficacy estimates.
A 9-month-old male presented to hospital with signs and symptoms of raised intracranial pressure. A CT scan showed obstructive hydrocephalus from a large pineal region mass lesion into which an intratumoral hemorrhage had occurred. A posterior fossa craniectomy and subtotal excision of the mass lesion were performed. By histopathology, the lesion was a malignant rhabdoid tumour (MRT). Despite surgery and chemotherapy, the tumour grew inexorably, and the patient died four months after the initial diagnosis. MRT is a rare and highly invasive neoplasm which infrequently arises from the central nervous system. This is the first documented case of a MRT arising from the pineal region. The clinical, radiographic, and pathological features of the MRT in this patient are presented.
Background: Population-based studies face challenges in measuring brain structure relative to cognitive aging. We examined the feasibility of acquiring state-of-the-art brain MRI images at a community hospital, and attempted to cross-validate two independent approaches to image analysis.
Methods: Participants were 49 older adults (29 cognitively normal and 20 with mild cognitive impairment (MCI)) drawn from an ongoing cohort study, with annual clinical assessments within one month of scan, without overt cerebrovascular disease, and without dementia (Clinical Dementia Rating (CDR) < 1). Brain MRI images, acquired at the local hospital using the Alzheimer's Disease Neuroimaging Initiative protocol, were analyzed using (1) a visual atrophy rating scale and (2) a semi-automated voxel-level morphometric method. Atrophy and volume measures were examined in relation to cognitive classification (any MCI and amnestic MCI vs. normal cognition), CDR (0.5 vs. 0), and presumed etiology.
Results: Measures indicating greater atrophy or lesser volume of the hippocampal formation, the medial temporal lobe, and the dilation of the ventricular space were significantly associated with cognitive classification, CDR = 0.5, and presumed neurodegenerative etiology, independent of the image analytic method. Statistically significant correlations were also found between the visual ratings of medial temporal lobe atrophy and the semi-automated ratings of brain structural integrity.
Conclusions: High quality MRI data can be acquired and analyzed from older adults in population studies, enhancing their capacity to examine imaging biomarkers in relation to cognitive aging and dementia.
We examine two different descriptions of the behavioral functions of the hippocampal system. One emphasizes spatially organized behaviors, especially those using cognitive maps. The other emphasizes memory, particularly working memory, a short-term memory that requires iexible stimulus-response associations and is highly susceptible to interference. The predictive value of the spatial and memory descriptions were evaluated by testing rats with damage to the hippocampal system in a series of experiments, independently manipulating the spatial and memory characteristics of a behavioral task. No dissociations were found when the spatial characteristics of the stimuli to be remembered were changed; lesions produced a similar deficit in both spatial and nonspatial test procedures, indicating that the hippocampus was similarly involved regardless of the spatial nature of the task. In contrast, a marked dissociation was found when the memory requirements were altered. Rats with lesions were able to perform accurately in tasks that could be solved exclusively on the basis of reference memory. They performed at chance levels and showed no signs of recovery even with extensive postoperative training in tasks that required working memory. In one experiment all the characteristics of the reference memory and working memory procedures were identical except the type of memory required. Consequently, the behavioral dissociation cannot be explained by differences in attention, motivation, response inhibition, or the type of stimuli to be remembered. As a result of these experiments we propose that the hippocampus is selectively involved in behaviors that require working memory, irrespective of the type of material (spatial or nonspatial) that is to be processed by that memory.
This chapter talks about a 61-year-old woman with a 5-year history of difficulty finding words and slowly progressive memory decline. At initial presentation, mood was good. General neurological exam was unremarkable. Language examination showed that spontaneous speech was fluent. Single photon emission computed tomography (SPECT) revealed reduced cortical perfusion in the left frontal, parietal, and temporal lobes compared to the right. The initial clinical impression was semantic dementia (SD). This senile dementia comprises one of the three clinical presentations of primary progressive aphasia (PPA). The other two are progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia. PPA has been recognized under several different labels and concepts over the last century. The term SD was coined in 1989 to describe three patients with fluent aphasia, impaired word comprehension and visual comprehension deficits. SD shows insidious onset and gradual progression that is characterized by understanding of word meaning and/or object identity.
Although memory deficits are typically the earliest and most profound symptoms of Alzheimer’s disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects. (JINS, 2009, 15, 751–757.)
Individuals infected with Human Immunodeficiency Virus (HIV) and having cognitive impairment have been described as having slow mentation. Data supporting this proposition come from a variety of sources, including Sternberg's (1966) item recognition memory task. The procedure nominally provides an index of speed of mental operations, independent from input/output demands. However, since the original use of this procedure in the 1960s, advances in cognitive psychology have revealed many of its limitations. The purpose of the present study was to examine the psychometric characteristics of this task. Each participant performed the Sternberg item recognition task twice, 6 mo apart. The stability of the estimate of the slope of regression equations and for zero intercept ranged from excellent (r = .87) to poor (r = .30), and the data from many individual subjects could not be reliably modelled using multiple linear regression techniques. These data, as well as those from previous research, demonstrate the limited practical use of this task in clinical samples. Furthermore, as cognitive psychological theory has advanced in the past 30 yr, the conceptual underpinnings of the procedure have essentially evaporated. (JINS, 1995, 1, 3–9).
The purpose of this study was to examine regional
cerebral blood flow using positron emission tomography
(PET) during the performance of tasks related to visual
confrontation naming. Ten healthy, young participants were
scanned twice in each of 5 conditions; blood flow was measured
using standard PET [15O]-water technology.
Two major findings have replicated previous studies. First,
the naming of visually presented objects, whether covert
or overt, requires a region of the left inferior cortex
including the fusiform gyrus. Second, during overt naming,
there is an increase in activity in the inferior or frontal
cortex and insula as a consequence of generating speech
code. These data are consistent with other studies demonstrating
the importance of the inferior temporal regions for semantic
processing, and the frontal cortex for word form generation.
(JINS, 1998, 4, 160–166.)
Individuals infected with the acquired immunodeficiency
syndrome (AIDS) are at risk for developing cognitive impairment.
The extent to which the impairment represents the results
of a single factor accounting for a wide degree of cognitive
dysfunction, or is the result of the combined effects of
multiple factors, has not been determined. In the present
study, we analyzed data from 134 patients with AIDS and
105 HIV− controls using a recently developed analytical
procedure. The results revealed that, by and large, the
test variables shared a significant amount of variance
related to disease status. Hence the AIDS-related influences
on cognition are shared and thus cannot be considered independent.
Two tests, Digit Symbol Substitution, and the primacy measure
of verbal free recall, had a direct relationship with the
group variable (AIDS vs. controls). These results
suggest that a single factor is sufficient to account for
a large proportion of the AIDS-related variance on a wide
variety of neuropsychological tests. (JINS, 1999,
Current views of long-term memory presume that
both the hippocampal complex and the neocortex play interactive,
but separate, roles in the storage of memories. While the
neocortex is considered the eventual and permanent store
for our memories, the encoding of recently experienced
events is thought to be initially dependent upon the hippocampus
and closely related structures. Neuropsychological studies
have demonstrated that damage to the medial temporal lobe
results in a retrograde amnesia extending back in time,
with better preservation of older memories. The converse
pattern has been shown in patients with semantic dementia,
who have focal atrophy of the inferolateral temporal neocortex,
but relative sparing of the hippocampal complex (Graham
& Hodges, 1997). Here we demonstrate that such patients
can show relatively preserved new learning on a forced-choice
recognition memory test (based on real and chimeric animals),
while patients in the early amnestic phase of Alzheimer's
disease show severely impaired learning on the same test.
This result provides support for the view that new learning
is primarily dependent upon the hippocampus and related
structures. (JINS, 1997, 3, 534–544.)
Neuropsychological and psychiatric evaluations were made of 39 subjects with possible Alzheimer's disease and a history of excessive alcohol consumption (AD + ETOH), who had been abstinent or had drunk minimally for at least three months before evaluation, and 225 patients with probable Alzheimer's disease (PAD) of comparable age, years of education, and baseline global impairment. At baseline, there were no significant differences between the groups in terms of age of onset of dementia, neuropsychological test scores, or current behavioural or psychiatric symptoms. One year later, no differences in rates of decline between 20 abstinent AD + ETOH patients and 88 PAD subjects could be shown. Thus, past heavy alcohol consumption does not appear to modify the presentation of dementia of the Alzheimer's type, nor does it modify progression over a one-year interval.
Immediate memory for visuospatial information was assessed in patients affected by Alzheimer-type dementia but with unimpaired visuo-perceptual functions. Patients were given two tasks: one was a traditional visuospatial memory task (Corsi's block tapping test), the second explored specifically immediate memory for visuospatial patterns. The experiment was conducted in two parallel groups of patients in Italy and the United States, each with its own appropriate sample of normal control subjects. Results showed a specific deficit of visual working memory in demented patients, even in a task in which control subjects achieved error-free performance. These data are interpreted in the light of the Working Memory Model, and suggest that in dementia the functions of the Visuospatial Scratchpad, unlike the functions of the verbal subsystems, may be impaired.
The memory deficit in Alzheimer's disease (AD) has been characterized as consisting of multiple components. The purpose of this study was to confirm the utility of a two-process model, and to examine changes in the nature and extent of the neuropsychological deficits after a one-year interval. The results replicate the initial observation that the memory loss in AD can be described as consisting of a focal amnesic syndrome and a dysexecutive syndrome characterized by failure of rapid information processing and search of both episodic and semantic memory. One year after the initial observation, all dysexecutive patients and the majority of the amnesic patients had become non-focal. No patient developed a dysexecutive syndrome, but 18 patients developed amnesic syndromes. These results suggest that, like other aspects of the cognitive deficits of AD, the memory loss is multifactorial. These results have implications for understanding the pathophysiology of AD, and for designing pharmacotherapeutic intervention.
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