Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 ...laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries.
We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012).
We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.
Van Buchem disease is an autosomal recessive disease characterized by overgrowth of the skeleton. In a group of Dutch patients the disease is thought to be due to a 52-kb deletion that results in ...decreased expression of the SOST gene. To further characterize the disease, the morphology of the metacarpals of six adult subjects and two juveniles with Van Buchem disease were measured on hand x-rays along with nine normal adults and nine adult carriers of the disease. Serum bone formation markers, alkaline phosphatase, type I procollagen peptide, and osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide, were determined. Van Buchem patients had increased metacarpal outer diameter, inner diameter, cortical thickness, and bone mineral density. Calculated bone volume and derived polar moment of inertia were markedly elevated (elevations of 158 ± 33% and 497 ± 95%, respectively) consistent with increased bone strength. Serum procollagen peptide and osteocalcin were significantly higher in Van Buchem patients. Urinary cross-linked N-telopeptide was significantly elevated in Van Buchem patients. None of these changes was found in Van Buchem carriers. These observations indicate that decreased expression of the SOST gene can lead to increased bone formation and to stronger bones.
NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small-vessel disease (SVD). While monoallelic ...cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients with biallelic variants in NOTCH3 are extremely rare and not well characterised.
In this study, we present clinical and genetic data from 25 patients with biallelic NOTCH3 variants and conduct a literature review of another 25 cases (50 patients in total). Brain magnetic resonance images (MRI) were analysed by expert neuroradiologists to better understand the phenotype associated with biallelic NOTCH3 variants.
Our systematic analyses verified distinct genotype-phenotype correlations for the two types of biallelic variants in NOTCH3. Biallelic loss-of-function variants (26 patients) lead to a neurodevelopmental disorder characterised by spasticity, childhood-onset stroke, and periatrial white matter volume loss resembling periventricular leukomalacia. Conversely, patients with biallelic cysteine-involving missense variants (24 patients) fall within CADASIL spectrum phenotype with early adulthood onset stroke, dementia, and deep white matter lesions without significant volume loss. White matter lesion volume is comparable between patients with biallelic cysteine-involving missense variants and individuals with CADASIL. Notably, monoallelic carriers of loss-of-function variants are predominantly asymptomatic, with only a few cases reporting nonspecific headaches.
We propose a NOTCH3-SVD classification depending on dosage and variant type. This study not only expands our knowledge of biallelic NOTCH3 variants but also provides valuable insight into the underlying mechanisms of the disease, contributing to a more comprehensive understanding of NOTCH3-related SVD.
The Wellcome Trust, the MRC.
The aim of this study was to estimate the production cost and economic indicators associated with the production and sales of fruits from 20 custard apple progenies during the initial five harvests, ...in order to identify the harvest season from which custard apple exploitation becomes profitable, as well as the most promising progenies from an economic point of view. The fruit yield data upon which the present work was based were obtained during the period from 2001 to 2005, in an experiment that evaluated 20 custard apple half-sibling progenies, under sprinkler irrigation. The progenies were evaluated in a random block design with five replicates and plots consisting of four plants each. The exploitation of custard apple progenies only showed to be a profitable agribusiness after the fourth year. Before that, only A3 and A4 progenies in the second year, and P3 and P11 in the third year provided profitable incomes. Considering the methodological assumptions imposed concerning the time period analysis and the prices as of July 2007, the most important profitability indicators (operating profit, return index and equilibrium price) evidenced that the A4 progeny is the most recommended, although other progenies are also highlighted, such as FJ1 and FJ2. As already discussed, the progenies showing the highest average yields of five harvests are not always the most economically recommendable ones.
The aim of this study was to estimate the production cost and economic indicators associated with the production and sales of fruits from 20 custard apple progenies during the initial five harvests, ...in order to identify the harvest season from which custard apple exploitation becomes profitable, as well as the most promising progenies from an economic point of view. The fruit yield data upon which the present work was based were obtained during the period from 2001 to 2005, in an experiment that evaluated 20 custard apple half-sibling progenies, under sprinkler irrigation. The progenies were evaluated in a random block design with five replicates and plots consisting of four plants each. The exploitation of custard apple progenies only showed to be a profitable agribusiness after the fourth year. Before that, only A3 and A4 progenies in the second year, and P3 and P11 in the third year provided profitable incomes. Considering the methodological assumptions imposed concerning the time period analysis and the prices as of July 2007, the most important profitability indicators (operating profit, return index and equilibrium price) evidenced that the A4 progeny is the most recommended, although other progenies are also highlighted, such as FJ1 and FJ2. As already discussed, the progenies showing the highest average yields of five harvests are not always the most economically recommendable ones.O presente trabalho tem como objetivo estimar o custo de produção e indicadores econômicos, relativos à produção e comercialização de frutos de 20 progênies de pinheiras, nas cinco primeiras safras, visando a identificar a safra a partir da qual a exploração da pinheira é lucrativa e as progênies mais promissoras, do ponto de vista econômico. Os dados de rendimentos de frutos em que se baseou o presente trabalho, foram obtidos no período de 2001 a 2005, em um experimento de avaliação de 20 progênies de meias-irmãs de pinheira, com irrigação por aspersão. As progênies foram avaliadas no delineamento de blocos aleatorizados, com cinco repetições e parcelas de quatro plantas. A exploração das progênies de pinheiras somente mostrou-se lucrativa a partir do quarto ano. Antes disso, somente as progênies A3 e A4, no segundo ano, e P3 e P11, no terceiro ano, geraram lucros satisfatórios. Nas pressuposições impostas na metodologia, com respeito ao período de análise temporal e aos preços tomados para julho de 2007, os mais importantes indicadores da lucratividade (lucro operacional, índice de rentabilidade e preço de equilíbrio) indicaram que a progênie A4 é a recomendada, embora outras progênies (FJ1 e FJ2) também tenham-se destacado. Nem sempre as progênies que apresentaram maior rendimento médio de frutos, nas cinco safras, são também as mais recomendáveis economicamente.
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