Global neonatal and perinatal mortality: a review and case study for the Loreto Province of Peru

Jamie B Warren,1 William E Lambert,2 Rongwei Fu,2 JoDee M Anderson,1 Alison B Edelman31Department of Pediatrics, 2Department of Public Health and Preventive Medicine, 3Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USABackground: Millennium Development Goal 4 calls for the reduction of the under-five mortality rate by two-thirds between 1990 and 2015. To reach this goal, neonatal mortality must be decreased. The lack of information on global neonatal and perinatal mortality impedes appropriate implementation of interventions, as vital registration systems are not available for the majority of the world's neonatal deaths. Verbal autopsy (VA) is a tool that has been used to determine cause of death. Recent studies have attempted to standardize and validate the use of this tool in resource-limited areas. The World Health Organization (WHO) International Standard VA Questionnaire was used to conduct a needs assessment in nine rural Peruvian villages. The goal was to determine the neonatal mortality rate (NMR), perinatal mortality rate (PMR), and causes of, and risk factors for, death in these villages.Methods: Eligible women were interviewed using the WHO International Standard VA Questionnaire or a set of questions based on the WHO VA Questionnaire. NMR and PMR were calculated using a generalized estimating equation model. Three neonatologists independently reviewed VA records to provide cause of death determination. Reviewer agreement was assessed using percent agreement. Fisher's exact test was used to determine risk factors associated with death.Results: The NMR was 31.4 per 1000 live births and the PMR was 49.7 per 1000 pregnancies. The main contributor to neonatal death was infection (43%). Percent agreement among reviewers was 90.5% and 38.9% for cause of neonatal death and stillbirth, respectively. Risk factors for death were pregnancy with twins (P = 0.001), preterm delivery (P = 0.003), and cesarean section delivery (P = 0.049).Conclusion: The WHO VA proved useful for NMR and PMR calculation, cause of death determination, and risk factor identification. Information gathered in this needs assessment will allow for the design and implementation of tailored interventions.Keywords: neonatal mortality, perinatal mortality, verbal autopsy, needs assessmen

Auditory spatial processing in Alzheimer's disease.

: The location and motion of sounds in space are important cues for encoding the auditory world. Spatial processing is a core component of auditory scene analysis, a cognitively demanding function that is vulnerable in Alzheimer's disease. Here we designed a novel neuropsychological battery based on a virtual space paradigm to assess auditory spatial processing in patient cohorts with clinically typical Alzheimer's disease (n = 20) and its major variant syndrome, posterior cortical atrophy (n = 12) in relation to healthy older controls (n = 26). We assessed three dimensions of auditory spatial function: externalized versus non-externalized sound discrimination, moving versus stationary sound discrimination and stationary auditory spatial position discrimination, together with non-spatial auditory and visual spatial control tasks. Neuroanatomical correlates of auditory spatial processing were assessed using voxel-based morphometry. Relative to healthy older controls, both patient groups exhibited impairments in detection of auditory motion, and stationary sound position discrimination. The posterior cortical atrophy group showed greater impairment for auditory motion processing and the processing of a non-spatial control complex auditory property (timbre) than the typical Alzheimer's disease group. Voxel-based morphometry in the patient cohort revealed grey matter correlates of auditory motion detection and spatial position discrimination in right inferior parietal cortex and precuneus, respectively. These findings delineate auditory spatial processing deficits in typical and posterior Alzheimer's disease phenotypes that are related to posterior cortical regions involved in both syndromic variants and modulated by the syndromic profile of brain degeneration. Auditory spatial deficits contribute to impaired spatial awareness in Alzheimer's disease and may constitute a novel perceptual model for probing brain network disintegration across the Alzheimer's disease syndromic spectrum.<br/

fMRI evidence for a cortical hierarchy of pitch pattern processing

Pitch patterns, such as melodies, consist of two levels of structure: a global level, comprising the pattern of ups and downs, or contour; and a local level, comprising the precise intervals that make up this contour. An influential neuropsychological model suggests that these two levels of processing are hierarchically linked, with processing of the global structure occurring within the right hemisphere in advance of local processing within the left. However, the predictions of this model and its anatomical basis have not been tested in neurologically normal individuals. The present study used fMRI and required participants to listen to consecutive pitch sequences while performing a same/different one-back task. Sequences, when different, either preserved (local) or violated (global) the contour of the sequence preceding them. When the activations for the local and global conditions were contrasted directly, additional activation was seen for local processing in right planum temporale and posterior superior temporal sulcus (pSTS). The presence of additional activation for local over global processing supports the hierarchical view that the global structure of a pitch sequence acts as a “framework” on which the local detail is subsequently hung. However, the lateralisation of activation seen in the present study, with global processing occurring in left pSTS and local processing occurring bilaterally, differed from that predicted by the neuroanatomical model. A re-examination of the individual lesion data on which the neuroanatomical model is based revealed that the lesion data equally well support the laterality scheme suggested by our data. While the present study supports the hierarchical view of local and global processing, there is an evident need for further research, both in patients and neurologically normal individuals, before an understanding of the functional lateralisation of local and global processing can be considered established

Data-Driven Sequence of Changes to Anatomical Brain Connectivity in Sporadic Alzheimer's Disease

Model-based investigations of transneuronal spreading mechanisms in neurodegenerative diseases relate the pattern of pathology severity to the brain’s connectivity matrix, which reveals information about how pathology propagates through the connectivity network. Such network models typically use networks based on functional or structural connectivity in young and healthy individuals, and only end-stage patterns of pathology, thereby ignoring/excluding the effects of normal aging and disease progression. Here, we examine the sequence of changes in the elderly brain’s anatomical connectivity over the course of a neurodegenerative disease. We do this in a data-driven manner that is not dependent upon clinical disease stage, by using event-based disease progression modeling. Using data from the Alzheimer’s Disease Neuroimaging Initiative dataset, we sequence the progressive decline of anatomical connectivity, as quantified by graph-theory metrics, in the Alzheimer’s disease brain. Ours is the first single model to contribute to understanding all three of the nature, the location, and the sequence of changes to anatomical connectivity in the human brain due to Alzheimer’s disease. Our experimental results reveal new insights into Alzheimer’s disease: that degeneration of anatomical connectivity in the brain may be a viable, even early, biomarker and should be considered when studying such neurodegenerative diseases

Molecular nexopathies: a new paradigm of neurodegenerative disease.

Neural networks provide candidate substrates for the spread of proteinopathies causing neurodegeneration, and emerging data suggest that macroscopic signatures of network disintegration differentiate diseases. However, how do protein abnormalities produce network signatures? The answer may lie with 'molecular nexopathies': specific, coherent conjunctions of pathogenic protein and intrinsic network characteristics that define network signatures of neurodegenerative pathologies. Key features of the paradigm that we propose here include differential intrinsic network vulnerability to propagating protein abnormalities, in part reflecting developmental structural and functional factors; differential vulnerability of neural connection types (e.g., clustered versus distributed connections) to particular pathogenic proteins; and differential impact of molecular effects (e.g., toxic-gain-of-function versus loss-of-function) on gradients of network damage. The paradigm has implications for understanding and predicting neurodegenerative disease biology

Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Physiological phenotyping of dementias using emotional sounds.

INTRODUCTION: Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. METHODS: Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). RESULTS: Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. DISCUSSION: Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development