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Studying the function of common genetic variants in primary human tissues and during development is challenging. To address this, we use an efficient multiplexing strategy to differentiate 215 human induced pluripotent stem cell (iPSC) lines toward a midbrain neural fate, including dopaminergic neurons, and use single-cell RNA sequencing (scRNA-seq) to profile over 1 million cells across three differentiation time points. The proportion of neurons produced by each cell line is highly reproducible and is predictable by robust molecular markers expressed in pluripotent cells. Expression quantitative trait loci (eQTL) were characterized at different stages of neuronal development and in response to rotenone-induced oxidative stress. Of these, 1,284 eQTL colocalize with known neurological trait risk loci, and 46% are not found in the Genotype–Tissue Expression (GTEx) catalog. Our study illustrates how coupling scRNA-seq with long-term iPSC differentiation enables mechanistic studies of human trait-associated genetic variants in otherwise inaccessible cell states. Single-cell RNA-seq analysis of iPSC neural differentiation identifies markers that predict line-to-line differences in cell fate potential and eQTLs that are specific to different stages of differentiation and that overlap with GWAS risk variants for neurological traits.

Collectivist Economics examines such issues as the inequality of the distribution of wealth and its impact on social stability, corrupt financial institutions and economic efficiency. Chapters covering industrial organization, unemployment, international trade, prices, remuneration, taxation and insurance, and local and national government form the main part of the book.

Collectivist Economics examines such issues as the inequality of the distribution of wealth and its impact on social stability, corrupt financial institutions and economic efficiency.

POLITICAL economists for several generations have been carrying on interminable discussions on the Theory of Value, which at least serve to show the futility of attempts to explore the labyrinthine tangle of the movements of prices under Capitalism. I t is true that, in the course of these investigations and discussions, light of scientific and practical value has been thrown on the nature of capitalist production and distribution, but the maze remains as much a mystery and inconvenience as ever. The economists have industriously tried to discover order in the confusion, and after eliminating all sorts of disturbing influences, have elaborated elusory \" Laws,\" which after all are of little practical value. They have much to say about the \" Normal,\" about \" Equilibrium,\" and so on. But these are only fictions existing in their imagination. In the capitalist system it is the abnormal that is normal, to borrow Bernard Shaw's witticism, and equilibrium simply does not exist. Constant fluctuation of prices leading now to the unemployment and ruin of producers, now to the impoverishment of consumers, is the normal situation ; and economists complacently try to discover the \" laws \" of this fluctuation, instead of devising an economic system that would be free from the factors that disturb \" equilibrium.\" Collectivism would provide the cure, is in fact the only form of property-holding and wealth production in an advanced and complicated industrial system with mass-production that can secure stable production, equitable distribution, and steady prices.

THE difficulty of ascertaining the principles according to which the product of labour ought to be divided between the workers, and of discovering a workable application of them, is perhaps greater than that of devising the economic mechanism of Collectivism. Collectivist production and exchange, the national ownership and management of practically all industrial concerns, it may be safely predicted, will be working smoothly long before there will be more than moderate satisfaction with the relative rates of pay for the innumerable kinds of work and service, and with the arrangements for securing equity of payment in the same occupation.

IN dealing with Taxation under Collectivism we must first inquire into the characters differentiating the services that ought to be supported by taxation from those vastly more numerous services that ought to be supported only by payments from the persons who choose to take the benefit of them, and only in proportion to that benefit. The Collectivist State, i t must be borne in mind, will carry on as national concerns practically all economic services, industrial and professional ; and i t is therefore necessary to discover the principle according to which services that ought to be supported by taxation can be distinguished from all others. Communists openly declare that their ideal is to have all services \" free,\" which can only mean of course that all services must be supported by taxation. This would lead inevitably to forced labour and rationing, which, if society were not totally wrecked, would result in waste, inefficiency, and virtual slavery. One of the best ways of combatting the pernicious doctrines of Communism is to formulate the fundamental principle of taxation, for i t justifies the making of only a few of the national services \" free,\" to use the word in the communistic sense, and by implication excludes all the others from that category. Let us consider one or two concrete cases of the two classes of services, and try to discover the distinctive features according to which they should be placed in the one class or the other.

IN the transition from Capitalism to Collectivism i t is essential that nothing should be done to disturb economic stabilitysuch as i t is. In the vital interest of the community the economic life must be conserved through all changes from the one system to the other. No violence must be used, nor any kind of action taken that leads to paralysis of production or distribution ; it is the first duty of every government to prevent this, and to preserve law and order. As the example of Russia shows, it would be infinitely better to endure the evils of the present system than, by a dictatorship of any kind, to compel the majority to conform to a system which they do not understand and are therefore unfit to make a success of. Blank ruin lies that way. The best must be made of the present system while the transition is in progress, and every change in the direction of Collectivism must only be made after the most careful consideration. All that collectivists can do is to try to show the way, and trust that the people will realise the seriousness of the situation, and set their minds to study it. Unfortunately, too little of the best intelligence is concentrated on the grave problems that press for solution ; the vast proportion of it is directed into other channels where it produces too little of real social value in present circumstances.

In fact, this is the Gordian knot of political economy, and there is only one way of dealing with it.\" Mechanism\" is a misnomer when applied to our present commercial, trading, banking, and financial arrangements. Such \" mechanism \" is far from being, as it might and would be in a properly organized community, well-designed, effective and smoothly working, with its movements easily followed ; it is a tangle that cannot be unravelled even by the most expert minds. For some generations political economists have been engaged in the work, and they are as far off as ever from the solution of the problems of the \" dismal science \" connected with money and exchange ; trying to evolve order out of the chaotic welter of individual interests and actions is worse than trying to square the circle or to discover perpetual motion. Economists accordingly are far from being unanimous in their theories of value, credit, currency, and international trade ; nor can they show how financial and commercial crises, bankruptcies, industrial depressions, unemployment, low wages, due so often to the present clumsy and ineffective \" mechanism \" of exchange, can be prevented in their individualist system. Practical men, too, bankers and financiers, those who have the handling and management ofthe money and the credit of the world, are unable owing to the intricacies of the capitalist system to solve the problems involved, even had they the best intentions. The economic results of their blundering and muddling are too often appallingly disastrous.