The causes and consequences of demographic transition

The causes and consequences of the demographic transition are considered in light of the recent book by Dyson (2010) on demography and development. In the last 50 years the world has seen an exogenous decline in mortality that generated a decline in fertility and an increase in urbanization that has had profound economic, social and political consequences. However, historically, declines in mortality and fertility, and escape from the Malthusian trap, have required countries to have already undergone considerable economic and political development. We therefore argue for two way causality between the demographic transition and economic and political outcomes

The Emergence of Three Human Development Clubs

We examine the joint distribution of levels of income per capita, life expectancy, and years of schooling across countries in 1960 and in 2000. In 1960 countries were clustered in two groups; a rich, highly educated, high longevity “developed” group and a poor, less educated, high mortality, “underdeveloped” group. By 2000 however we see the emergence of three groups; one underdeveloped group remaining near 1960 levels, a developed group with higher levels of education, income, and health than in 1960, and an intermediate group lying between these two. This finding is consistent with both the ideas of a new “middle income trap” that countries face even if they escape the “low income trap”, as well as the notion that countries which escaped the poverty trap form a temporary “transition regime” along their path to the “developed” group

The effect of vaccination on children's physical and cognitive development in the Philippines

We use data from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) in the Philippines to link vaccination in the first 2 years of life with later physical and cognitive development in children. We use propensity score matching to estimate the causal effect of vaccination on child development. We find no effect of vaccination on later height or weight, but full childhood vaccination for measles, polio, Tuberculosis (TB), Diphtheria, Pertussis and Tetanus (DPT) significantly increases cognitive test scores relative to matched children who received no vaccinations. The size of the effect is large, raising test scores, on average, by about half an SD

B-Amyloid of Alzheimer\u27s Disease Induces Reactive Gliosis that Inhibits Axonal Outgrowth

Pathological lesions in the brains of patients with Alzheimer\u27s disease (AD) are characterized by dense deposits of the protein ,B-amyloid. The link between the deposition of B-amyloid in senile plaques and AD-associated pathology is, at present, controversial since there have been conflicting reports on whether the 39- 43 amino acid B-amyloid sequence is toxic or trophic to neurons. In this report, we show that B-amyloid peptide when presented as an insoluble substrate which mimics its conformation in vivo can induce cortical glial cells in vitro and in vivo to locally deposit chondroitin sulfate containingproteoglycan. In vitro the proteoglycan-containing matrix deposited by glia on B-amyloid blocks the usual ability of the peptide to allow cortical neurons to adhere and grow. Chondroitin sulfate-containing proteoglycan was also found in senile plaques of human AD tissue. We suggest that an additional effect of B-amyloid in the brain, which compounds the direct effects of ,8- amyloid on neurons, is mediated by the stimulation of astroglia to become reactive. Once in the reactive state, glial cells deposit large amounts of growth-inhibitory molecules within the neuropil which could impair neuronal process survival and regeneration leading to neurite retraction and/or dystrophy around senile plaques in AD

Inhibition of glycolysis and mitochondrial respiration promotes radiosensitisation of neuroblastoma and glioma cells

Background: Neuroblastoma accounts for 7% of paediatric malignancies but is responsible for 15% of all childhood cancer deaths. Despite rigorous treatment involving chemotherapy, surgery, radiotherapy and immunotherapy, the 5-year overall survival rate of high-risk disease remains < 40%, highlighting the need for improved therapy. Since neuroblastoma cells exhibit aberrant metabolism, we determined whether their sensitivity to radiotherapy could be enhanced by drugs affecting cancer cell metabolism. Methods: Using a panel of neuroblastoma and glioma cells, we determined the radiosensitising effects of inhibitors of glycolysis (2-DG) and mitochondrial function (metformin). Mechanisms underlying radiosensitisation were determined by metabolomic and bioenergetic profiling, flow cytometry and live cell imaging and by evaluating different treatment schedules. Results: The radiosensitising effects of 2-DG were greatly enhanced by combination with the antidiabetic biguanide, metformin. Metabolomic analysis and cellular bioenergetic profiling revealed this combination to elicit severe disruption of key glycolytic and mitochondrial metabolites, causing significant reductions in ATP generation and enhancing radiosensitivity. Combination treatment induced G2/M arrest that persisted for at least 24 h post-irradiation, promoting apoptotic cell death in a large proportion of cells. Conclusion: Our findings demonstrate that the radiosensitising effect of 2-DG was significantly enhanced by its combination with metformin. This clearly demonstrates that dual metabolic targeting has potential to improve clinical outcomes in children with high-risk neuroblastoma by overcoming radioresistance

Lipoprotein-associated phosphoplipase a2 (lp-pla2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA(2), darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA(2) and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood–retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA(2) inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA(2) inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA(2) may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents

Methods applied to neonatal dried blood spot samples for secondary research purposes:a scoping review

This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e. research not related to newborn screening for inherited genetic and metabolic disorders) were identified from six electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PubMed and Scopus. Inclusion was restricted to studies published from 1973 and written in or translated into English that reported the storage, extraction and testing of neonatal DBS samples. Sixty-seven studies were eligible for inclusion. Included studies were predominantly methodological in nature and measured various analytes, including nucleic acids, proteins, metabolites, environmental pollutants, markers of prenatal substance use and medications. Neonatal DBS samples were stored over a range of temperatures (ambient temperature, cold storage or frozen) and durations (two weeks to 40.5 years), both of which impacted the recovery of some analytes, particularly amino acids, antibodies and environmental pollutants. The size of DBS sample used and potential contamination were also cited as methodological limitations. Residual neonatal DBS samples retained by newborn screening programs are a promising resource for secondary research purposes, with many studies reporting the successful measurement of analytes even from neonatal DBS samples stored for long periods of time in suboptimal temperatures and conditions.</p

The pill questionnaire in a nondemented Parkinson's disease population

We assessed the Pill Questionnaire as a screen for mild cognitive impairment in nondemented Parkinson's disease patients. The relationship between ability to remember medications for Parkinson's disease in the Pill Questionnaire, mild cognitive impairment, and deficits on neuropsychological tests performed 2–3 weeks later blind to Pill Questionnaire results was assessed in movement disorders clinic patients. In 109 subjects, inaccurate medication reporting on the Pill Questionnaire was associated with lower scores on the Montreal Cognitive Assessment, Scales for Outcomes in Parkinson's Disease–Cognition and with deficits in memory, attention, executive function‐inhibitory control, processing speed, visuospatial function, and language. Inaccurate medication reporting was also associated with an adjusted odds ratio of 2.4 (95% CI, 0.91–5.88; P = .06) for mild cognitive impairment, with a specificity of 80% and sensitivity of 41%. The Pill Questionnaire is neither sensitive nor specific enough to be used as the sole screening or diagnostic tool for mild cognitive impairment. However, inaccurate medication reporting is associated with deficits spanning many cognitive domains and should alert a clinician to a higher likelihood of cognitive impairment. © 2012 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93736/1/25124_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93736/2/MDS_25124_sm_SuppTables.pd

Universal features in the growth dynamics of complex organizations

We analyze the fluctuations in the gross domestic product (GDP) of 152 countries for the period 1950--1992. We find that (i) the distribution of annual growth rates for countries of a given GDP decays with ``fatter'' tails than for a Gaussian, and (ii) the width of the distribution scales as a power law of GDP with a scaling exponent $\beta \approx 0.15$. Both findings are in surprising agreement with results on firm growth. These results are consistent with the hypothesis that the evolution of organizations with complex structure is governed by similar growth mechanisms.Comment: 4 pages, 7 ps figures, using Latex2e with epsf rotate and multicol style files. Submitted to PR

A Giant Metrewave Radio Telescope/Chandra view of IRAS 09104+4109: A type 2 QSO in a cooling flow

IRAS 09104+4109 is a rare example of a dust enshrouded type 2 QSO in the centre of a cool-core galaxy cluster. Previous observations of this z=0.44 system showed that as well as powering the hyper-luminous infrared emission of the cluster-central galaxy, the QSO is associated with a double-lobed radio source. However, the steep radio spectral index and misalignment between the jets and ionised optical emission suggested that the orientation of the QSO had recently changed. We use a combination of new, multi-band Giant Metrewave Radio Telescope observations and archival radio data to confirm that the jets are no longer powered by the QSO, and estimate their age to be 120-160 Myr. This is in agreement with the ~70-200 Myr age previously estimated for star-formation in the galaxy. Previously unpublished Very Long Baseline Array data reveal a 200 pc scale double radio source in the galaxy core which is more closely aligned with the current QSO axis and may represent a more recent period of jet activity. These results suggest that the realignment of the QSO, the cessation of jet activity, and the onset of rapid star-formation may have been caused by a gas-rich galaxy merger. A Chandra X-ray observation confirms the presence of cavities associated with the radio jets, and we estimate the energy required to inflate them to be ~7.7x10^60 erg. The mechanical power of the jets is sufficient to balance radiative cooling in the cluster, provided they are efficiently coupled to the intra-cluster medium (ICM). We find no evidence of direct radiative heating and conclude that the QSO either lacks the radiative luminosity to heat the ICM, or that it requires longer than 100-200 Myr to significantly impact its environment. [Abridged]Comment: 23 pages, 18 figures and 7 tables. Accepted for publication in MNRA