Low-dose ipilimumab plus nivolumab combined with IL-2 and hyperthermia in cancer patients with advanced disease: exploratory findings of a case series of 131 stage IV cancers - a retrospective study of a single institution.

The 3-year overall survival (OS) rate of patients with previously treated or untreated stage III or IV melanoma has by now reached 63% using ipilimumab and nivolumab therapy. However, immune-related adverse events (irAEs) of grade 3 or 4 occurred in 59% of patients leading to discontinuation of therapy in 24.5% of patients and one death. Therapy with checkpoint inhibitors could be safer and more effective in combination with hyperthermia and fever inducing therapies. We conducted a retrospective analysis to test the safety and efficacy of a new combination immune therapy in 131 unselected stage IV solid cancer patients with 23 different histological types of cancer who exhausted all conventional treatments. Treatment consisted of locoregional- and whole-body hyperthermia, individually dose adapted interleukin 2 (IL-2) combined with low-dose ipilimumab (0.3 mg/kg) plus nivolumab (0.5 mg/kg). The objective response rate (ORR) was 31.3%, progression-free survival (PFS) was 10 months, survival probabilities at 6 months was 86.7% (95% CI, 81.0-92.8%), at 9 months was 73.5% (95% CI, 66.2-81.7%), at 12 months was 66.5% (95% CI, 58.6-75.4%), while at 24 months survival was 36.6% (95% CI:28.2%; 47.3%). irAEs of World Health Organization (WHO) Toxicity Scale grade 1, 2, 3, and 4 were observed in 23.66%, 16.03%, 6.11%, and 2.29% of patients, respectively. Our results suggest that the irAEs profile of the combined treatment is safer than that of the established protocols without compromising efficacy.

The developmental implications of migration from and between small island nations.

PIP: This article discusses the role of migration in relieving population pressures, thus making continuing development possible, using small nations in the Caribbean and the South Pacific as examples. The Caribbean islands and many Pacific islands have used out-migration to ease population pressures in this century. Surplus labor has been emerging in various Caribbean nations, independent of the international marketing problems of plantation agriculture. Rural populations alienated from plantations have had to make do on questionable and/or remote land. Population surpluses appear to originate in rural areas, but little evidence exists to suggest that those surpluses are the basis for the emigration patterns of the Caribbean islands. Emigration does not solve population problems because when ambitious, skilled workers leave their country, their actions have little to do with the existence of domestic surplus labor and their leaving may do little to facilitate domestic labor absorption. Thus, if mini-states wish to sustain their hopes of economic expansion, they must find the means to employ their surplus labor. Since mainly skilled migrants leave, their going may actually slow development and retard opportunities for labor absorption. Population movements internal to the Caribbean region may further complicate surplus labor and/or population problems. If protective entry requirements impede normal inter-island relations, they may interfere with developmental processes. In general, migration is not a feasible strategy for population control for small island nations. While temporary migration has a more positive impact than other forms of migration, problems do exist. For example, temporary migration 1) can impose significant economic costs on the source-country, and 2) may result in the source country being unable to capitalize on its initial investment in training and education of temporary migrants. In conclusion, import substitution through cooperation between small island nations, production for export where feasible, and more attention to more sophisticated international service linkages hold a better prospect for material progress than relying on the export of surplus populations.^ieng

Argentina and the brain drain: some perspectives from expatriates in the United States.

PIP: This study focuses on the brain drain of health care professionals and physical scientists from Argentina, using survey data on a group of 89 immigrants who are currently US residents and listed in the current edition of AMERICAN MEN AND WOMEN OF SCIENCE. Although the loss of educated people is probably more likely if their degrees are acquired abroad, even at the doctoral level, the majority of those responding held Argentine degrees. The most important motivation was to gain professional and career advancement. Although pragmatism was associated with the decision to emigrate, the political environment was also quite important. Responses indicate that the losses of scientific personnel which have occurred in the past may be irreversible. Most of the respondents have become US citizens and now have families in that country. However, many respondents still have family, friends, or professional associations in Argentina. Some subtleties bear mention. The retreat of the generals has not removed all political factors from the problem list. Now scientific and professional activities must be de-politicized. The government must take explicit steps to ensure that academic and scientific positions are awarded on the basis of expertise. The evidence suggests that educational considerations are far less important as a causal element in the brain drain from Argentina than is the case in many Third World countries.^ieng

[Problems resulting from the absorption of small towns into urban areas in major Third World cities]. / Problemes poses par l'absorption des petites villes dans les zones urbaines des metropoles du Tiers Monde.

PIP: The tendency toward hypertrophy of large metropolitan areas in the Third World has been a subject of concern to economists and other social scientists for some time. Inability to absorb vast waves of migrants into the organized labor force or to provide adequate infrastructure and services are serious problems in many growing cities of Asia, Africa, and Latin America. A different phenomenon created by perpetual urban expansion has been relatively neglected: the problems caused when preexisting urban areas are absorbed into the metropolis. The tendency of squatter settlements to constrict normal urban growth and expansion and to impede rational provision of services has been recognized, but the absorption of small cities does not necessarily produce identical problems. Small cities absorbed into a metropolis lose their identity in the successive waves of suburban proliferation. Los Angeles in the US may be considered the prototype of the phenomenon in which multiple preexisting urban zones are absorbed into the same metropolis without formation of any visible center of gravity. In some cases, small cities may be completely engulfed by the encroaching metropolis, if transit routes or availability of land makes them interesting to developers. The livelihood of residents may be threatened if they are no longer able to cultivate gardens or raise small animals. Local services may deteriorate. The youngest and most able residents are likely to abandon such places for the greater opportunities of the city, leaving the aged and less qualified to fend for themselves. Jobs may disappear and traditional commercial relations may be destroyed without being replaced. The future wellbeing of residents depends on their ability to maneuver in the new metropolitan environment, but many will be unable to adjust for lack of training, the weight of immovable property, or diverse personal considerations. Planning could help to reduce the problems that occasional survival of some small entities may pose for rational expansion of transportation and services at the metropolitan level, but many Third World cities lack such planning capacity altogether.^ieng

Some specifics on the brain drain from the Andean region.

PIP: An analysis of the brain drain from the Andean countries of Bolivia, Chile, Colombia, Ecuador, and Peru to the United States is presented. The data are from a survey of 62 persons from those countries who are currently residing in the United States and are listed in the current edition of "American Men and Women of Science". The reasons why they left their country of origin and are staying in the United States are considered. (summary in FRE, SPA)^ieng

Some specifics on the loss of professional personnel from the Commonwealth Caribbean.

PIP: The present study is concerned with migration from the Commonwealth Caribbean to the United States. The focus is on the migration of professionals, or the brain drain.^ieng