On the human capital of Inca Indios before and after the Spanish conquest: Was there a "pre-colonial legacy"?

Not only the colonial period, but also the pre-colonial times might have influenced later development patterns. In this study we assess a potential pre-colonial legacy hypothesis for the case of the Andean region. In order to analyze the hypothesis, we study the human capital of Inca Indios, using age-heaping-based techniques to estimate basic numeracy skills. We find that Peruvian Inca Indios had only around half the numeracy level of the Spanish invaders. The hypothesis holds even after adjusting for a number of potential biases. Moreover, the finding has also crucial implications for the narrative of the military crisis of the Inca Empire. A number of explanations have been given as to why the Old American Empires were not able to defend their territory against the Spanish invaders in the early 16th century. We add an economic hypothesis to the debate and test it with new evidence: Were the human capital formation efforts of the Inca economy perhaps too limited, making it difficult to react appropriately to the Spanish challenge? --human capital,age-heaping,Inca empire,inequality,growth

Do you have to be tall and educated to be a migrant? Evidence from Spanish recruitment records, 1890-1950

We use Spanish military records stemming from the late-19th to the mid-20th century to assess internal migrants' self-selection. We find that migrants were, on average over the whole period, around one centimeter taller than non-migrants, and in the booming 1920s, the height advantage of movers reached three centimeters. The positive self-selection was larger for migrants originating in poorer provinces and traveling longer distances. A further finding is that migrants were positively selected in terms of literacy and socio-economic status according to their occupation. Professionals were most likely to have migrated internally and farmers least

Numeracy of religious minorities in Spain and Portugal during the Inquisition era

We assess the numeracy (age heaping) of religious minorities, particularly Jews, and other defendants of the Spanish and Portuguese Inquisitions, and compare it with the general Iberian population. Our database includes 13,000 individuals who took part in Inquisition trials, and 17,000 individuals recorded in censuses and parish registers who serve as a control group. We thoroughly discuss the representativeness of our samples for the populations we aim to capture. Our results point at a substantial numeracy advantage of the Judaism-accused over the Catholic majority. Furthermore, Catholic priests and other groups of the religious elite who were occasional targets of the Inquisition had a similarly high level of numeracy.Estimamos las capacidades numéricas (numeracy) de minorías religiosas -judíos en particular- y otros reos de la Inquisición Española y Portuguesa, y las comparamos con el resto de la población ibérica. Nuestra base de datos incluye 13.000 individuos que participaron en juicios de la Inquisición, y 17.000 individuos recogidos en censos y registros parroquiales que sirven de grupo de control. Discutimos minuciosamente la representatividad de nuestras muestras para las poblaciones en cuestión. Nuestros resultados apuntan a una ventaja sustancial de los acusados de judaísmo con respecto a la mayoría católica. Asimismo, los sacerdotes católicos y otros grupos religiosos elitistas, que fueron el blanco de la Inquisición, tenían un nivel alto de habilidades numéricas

Effects of multiple-dose ponesimod, a selective SIP1 receptor modulator, on lymphocyte subsets in healthy humans

This study investigated the effects of ponesimod, a selective SIP1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days) or placebo (ratio 3: 1). The overall change from baseline in lymphocyte count was -1,292 +/- 340x10(6) cells/L and 275 +/- 486x10(6) cells/L in ponesimod- and placebo-treated subjects, respectively. This included a decrease in both T and B lymphocytes following ponesimod treatment. A decrease in naive CD4(+) T cells (CD45RA(+)CCR7(+)) from baseline was observed only after ponesimod treatment (-113 +/- 98x10(6) cells/L, placebo: 0 +/- 18x10(6) cells/L). The number of T-cytotoxic (CD3(+)CD8(+)) and T-helper (CD3(+)CD4(+)) cells was significantly altered following ponesimod treatment compared with placebo. Furthermore, ponesimod treatment resulted in marked decreases in CD4(+) T-central memory (CD45RA(-)CCR7(+)) cells (-437 +/- 164x10(6) cells/L) and CD4(+) T-effector memory (CD45RA(-)CCR7(-)) cells (-131 +/- 57x10(6) cells/L). In addition, ponesimod treatment led to a decrease of -228 +/- 90x10(6) cells/L of gut-homing T cells (CLA(-)integrin beta 7(+)). In contrast, when compared with placebo, CD8(+) T-effector memory and natural killer (NK) cells were not significantly reduced following multiple-dose administration of ponesimod. In summary, ponesimod treatment led to a marked reduction in overall T and B cells. Further investigations revealed that the number of CD4(+) cells was dramatically reduced, whereas CD8(+) and NK cells were less affected, allowing the body to preserve critical viral-clearing functions

On the Human Capital of Inca Indios before and after the Spanish Conquest. Was there a “Pre-Colonial Legacy”?

Not only the colonial period, but also the pre-colonial times might have influenced later development patterns. In this study we assess a potential “pre-colonial legacy” hypothesis for the case of the Andean region. In order to analyze the hypothesis, we study the human capital of Inca Indios, using age-heaping-based techniques to estimate basic numeracy skills. We find that Peruvian Inca Indios had only around half the numeracy level of the Spanish invaders. The hypothesis holds even after adjusting for a number of potential biases. Moreover, the finding has also crucial implications for the narrative of the military crisis of the Inca Empire. A number of explanations have been given as to why the Old American Empires were not able to defend their territory against the Spanish invaders in the early 16th century. We add an economic hypothesis to the debate and test it with new evidence: Were the human capital formation efforts of the Inca economy perhaps too limited, making it difficult to react appropriately to the Spanish challenge

Long-lasting spinal oxytocin analgesia is ensured by the stimulation of allopregnanolone synthesis which potentiates GABA(A) receptor-mediated synaptic inhibition.

Hypothalamospinal control of spinal pain processing by oxytocin (OT) has received a lot of attention in recent years because of its potency to reduce pain symptoms in inflammatory and neuropathic conditions. However, cellular and molecular mechanisms underlying OT spinal antinociception are still poorly understood. In this study, we used biochemical, electrophysiological, and behavioral approaches to demonstrate that OT levels are elevated in the spinal cord of rats exhibiting pain symptoms, 24 h after the induction of inflammation with an intraplantar injection of λ-carrageenan. Using a selective OT receptor antagonist, we demonstrate that this elevated OT content is responsible for a tonic analgesia exerted on both mechanical and thermal modalities. This phenomenon appeared to be mediated by an OT receptor-mediated stimulation of neurosteroidogenesis, which leads to an increase in GABA(A) receptor-mediated synaptic inhibition in lamina II spinal cord neurons. We also provide evidence that this novel mechanism of OT-mediated spinal antinociception may be controlled by extracellular signal-related protein kinases, ERK1/2, after OT receptor activation. The oxytocinergic inhibitory control of spinal pain processing is emerging as an interesting target for future therapies since it recruits several molecular mechanisms, which are likely to exert a long-lasting analgesia through nongenomic and possibly genomic effects.journal articleresearch support, non-u.s. gov't2013 Oct 16importe

Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes

Aims  To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). Methods and results  In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4–11%). Conclusions  Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable

Women of an uncertain age: quantifying human capital accumulation in rural Ireland in the nineteenth century

Geary and Stark find that Ireland's post-Famine per capita GDP converged with British levels, and that this convergence was largely due to total factor productivity growth rather than mass emigration. In this article, new long-run measurements of human capital accumulation in Ireland are devised in order to facilitate a better assessment of sources of this productivity growth, including the relative contribution of men and women. This is done by exploiting the frequency at which age data heap at round ages, widely interpreted as an indicator of a population's basic numeracy skills. Because Földvári, van Leeuwen, and van Leeuwen-Li find that gender-specific trends in this measure derived from census returns are biased by who is reporting and recording the age information, any computed numeracy trends are corrected using data from prison and workhouse registers, sources in which women ostensibly self-reported their age. The findings show that rural Irish women born early in the nineteenth century had substantially lower levels of human capital than uncorrected census data would otherwise suggest. These results are large in magnitude and thus economically significant. The speed at which women converged is consistent with Geary and Stark's interpretation of Irish economic history; Ireland probably graduated to Europe's club of advanced economies thanks in part to rapid advances in female human capital

Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CPG of the rat spinal cord in vitro.

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 \u3bcM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits