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

On a Subposet of the Tamari Lattice

We explore some of the properties of a subposet of the Tamari lattice introduced by Pallo, which we call the comb poset. We show that three binary functions that are not well-behaved in the Tamari lattice are remarkably well-behaved within an interval of the comb poset: rotation distance, meets and joins, and the common parse words function for a pair of trees. We relate this poset to a partial order on the symmetric group studied by Edelman.Comment: 21 page

A Framework for Generalising the Newton Method and Other Iterative Methods from Euclidean Space to Manifolds

The Newton iteration is a popular method for minimising a cost function on Euclidean space. Various generalisations to cost functions defined on manifolds appear in the literature. In each case, the convergence rate of the generalised Newton iteration needed establishing from first principles. The present paper presents a framework for generalising iterative methods from Euclidean space to manifolds that ensures local convergence rates are preserved. It applies to any (memoryless) iterative method computing a coordinate independent property of a function (such as a zero or a local minimum). All possible Newton methods on manifolds are believed to come under this framework. Changes of coordinates, and not any Riemannian structure, are shown to play a natural role in lifting the Newton method to a manifold. The framework also gives new insight into the design of Newton methods in general.Comment: 36 page

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Degeneracy: a link between evolvability, robustness and complexity in biological systems

A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology. This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present evidence that degeneracy is a fundamental source of robustness, it is intimately tied to multi-scaled complexity, and it establishes conditions that are necessary for system evolvability

Field-induced polarisation of Dirac valleys in bismuth

Electrons are offered a valley degree of freedom in presence of particular lattice structures. Manipulating valley degeneracy is the subject matter of an emerging field of investigation, mostly focused on charge transport in graphene. In bulk bismuth, electrons are known to present a threefold valley degeneracy and a Dirac dispersion in each valley. Here we show that because of their huge in-plane mass anisotropy, a flow of Dirac electrons along the trigonal axis is extremely sensitive to the orientation of in-plane magnetic field. Thus, a rotatable magnetic field can be used as a valley valve to tune the contribution of each valley to the total conductivity. According to our measurements, charge conductivity by carriers of a single valley can exceed four-fifth of the total conductivity in a wide range of temperature and magnetic field. At high temperature and low magnetic field, the three valleys are interchangeable and the three-fold symmetry of the underlying lattice is respected. As the temperature lowers and/or the magnetic field increases, this symmetry is spontaneously lost. The latter may be an experimental manifestation of the recently proposed valley-nematic Fermi liquid state.Comment: 14 pages + 5 pages of supplementary information; a slightly modified version will appear as an article in Nature physic

Simultaneous TE Analysis of 19 Heliconiine Butterflies Yields Novel Insights into Rapid TE-Based Genome Diversification and Multiple SINE Births and Deaths

Transposable elements (TEs) play major roles in the evolution of genome structure and function. However, because of their repetitive nature, they are difficult to annotate and discovering the specific roles they may play in a lineage can be a daunting task. Heliconiine butterflies are models for the study of multiple evolutionary processes including phenotype evolution and hybridization. We attempted to determine how TEs may play a role in the diversification of genomes within this clade by performing a detailed examination of TE content and accumulation in 19 species whose genomes were recently sequenced. We found that TE content has diverged substantially and rapidly in the time since several subclades shared a common ancestor with each lineage harboring a unique TE repertoire. Several novel SINE lineages have been established that are restricted to a subset of species. Furthermore, the previously described SINE, Metulj, appears to have gone extinct in two subclades while expanding to significant numbers in others. This diversity in TE content and activity has the potential to impact how heliconiine butterflies continue to evolve and diverge

Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

Dopamine Inhibits Mitochondrial Motility in Hippocampal Neurons

The trafficking of mitochondria within neurons is a highly regulated process. In an earlier study, we found that serotonin (5-HT), acting through the 5-HT1A receptor subtype, promotes axonal transport of mitochondria in cultured hippocampal neurons by increasing Akt activity, and consequently decreasing glycogen synthase kinase (GSK3beta) activity. This finding suggests a critical role for neuromodulators in the regulation of mitochondrial trafficking in neurons. In the present study, we investigate the effects of a second important neuromodulator, dopamine, on mitochondrial transport in hippocampal neurons.Here, we show that dopamine, like 5-HT, regulates mitochondrial motility in cultured hippocampal neurons through the Akt-GSK3beta signaling cascade. But, in contrast to the stimulatory effect of 5-HT, administration of exogenous dopamine or bromocriptine, a dopamine 2 receptor (D2R) agonist, caused an inhibition of mitochondrial movement. Moreover, pretreatment with bromocriptine blocked the stimulatory effect of 5-HT on mitochondrial movement. Conversely, in cells pretreated with 5-HT, no further increases in movement were observed after administration of haloperidol, a D2R antagonist. In contrast to the effect of the D2R agonist, addition of SKF38393, a dopamine 1 receptor (D1R) agonist, promoted mitochondrial transport, indicating that the inhibitory effect of dopamine was actually the net summation of opposing influences of the two receptor subtypes. The most pronounced effect of dopamine signals was on mitochondria that were already moving directionally. Western blot analysis revealed that treatment with either a D2R agonist or a D1R antagonist decreased Akt activity, and conversely, treatment with either a D2R antagonist or a D1R agonist increased Akt activity.Our observations strongly suggest a role for both dopamine and 5-HT in regulating mitochondrial movement, and indicate that the integrated effects of these two neuromodulators may be important in determining the distribution of energy sources in neurons