The Population Factor in Africa's Development Dilemma.

Despite several decades of international effort, the development problems of sub-Saharan Africa remain acute. By many of the quality of life indexes, the majority of African countries are standing still or moving backward. A rapidly growing population with an adverse dependency ratio places demands on services that present development strategies cannot satisfy. A reorientation of development is necessary to establish realistic population policies and to implement comprehensive family planning programs.

MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis.

PURPOSE: Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-naïve non-small cell lung carcinoma (NSCLC). EXPERIMENTAL DESIGN: Six hundred eighty-seven NSCLCs were tested for MET exon 14 splicing site mutation (METΔ14), DNA copy number alterations, and protein expression by Sanger sequencing, FISH, and IHC, respectively. RESULTS: METΔ14 mutation was detected in 2.62% (18/687) of NSCLC. The mutation rates were 2.6% in adenocarcinoma, 4.8% in adenosquamous carcinoma, and 31.8% in sarcomatoid carcinoma. METΔ14 mutation was not detected in squamous cell carcinoma, large cell carcinoma, and lymphoepithelioma-like carcinoma but significantly enriched in sarcomatoid carcinoma (P < 0.001). METΔ14 occurred mutually exclusively with known driver mutations but tended to coexist with MET amplification or copy number gain (P < 0.001). Low-level MET amplification and polysomy might occur in the background of EGFR or KRAS mutation whereas high-level amplification (MET/CEP7 ratio ≥5) was mutually exclusive to the major driver genes except METΔ14. Oncogenic METΔ14 mutation and/or high-level amplification occurred in a total of 3.3% (23/687) of NSCLC and associated with higher MET protein expression. METΔ14 occurred more frequently in older patients whereas amplification was more common in ever-smokers. Both METΔ14 and high-level amplification were independent prognostic factors that predicted poorer survival by multivariable analysis. CONCLUSIONS: The high incidence of METΔ14 mutation in sarcomatoid carcinoma suggested that MET inhibition might benefit this specific subgroup of patients. Clin Cancer Res; 22(12); 3048-56. ©2016 AACRSee related commentary by Drilon, p. 2832.

Profiling of Oncogenic Driver Events in Lung Adenocarcinoma Revealed MET Mutation as Independent Prognostic Factor.

INTRODUCTION: Oncogenic driver mutations activating receptor tyrosine kinase pathways are promising predictive markers for targeted treatment. We investigated the mutation profile of an updated driver events list on receptor tyrosine kinase/RAS/PI3K axis and the clinicopathologic implications in a cohort of never-smoker predominated Chinese lung adenocarcinoma. METHODS: We tested 154 lung adenocarcinomas and adenosquamous carcinomas for EGFR, KRAS, HER2, BRAF, PIK3CA, MET, NRAS, MAP2K1, and RIT1 mutations by polymerase chain reaction-direct sequencing. MET amplification and ALK and ROS1 translocations were assessed by fluorescent in situ hybridizations. MET and thyroid transcription factor-1 protein expressions were investigated by immunohistochemistry. RESULTS: Seventy percent of lung adenocarcinomas carried actionable driver events. Alterations on EGFR (43%), KRAS (11.4%), ALK (6%), and MET (5.4%) were frequently found. ROS1 translocation and mutations involving BRAF, HER2, NRAS, and PIK3CA were also detected. No mutation was observed in RIT1 and MAP2K1. Patients with EGFR mutations had a favorable prognosis, whereas those with MET mutations had poorer overall survival. Multivariate analysis further demonstrated that MET mutation was an independent prognostic factor. Although MET protein expression was detected in 65% of lung adenocarcinoma, only 10% of the MET-immunohistochemistry positive tumors harbor MET DNA alterations that drove protein overexpression. Appropriate predictive biomarker is essential for selecting patients who might benefit from specific targeted therapy. CONCLUSION: Actionable driver events can be detected in two thirds of lung adenocarcinoma. MET DNA alterations define a subset of patients with aggressive diseases that might potentially benefit from anti-MET targeted therapy. High negative predictive values of thyroid transcription factor-1 and MET expression suggest potential roles as surrogate markers for EGFR and/or MET mutations.

Regional viewpoints on population growth: perspectives of the genocide issue.

PIP: Genocide implies an effort by the white races to reduce the number of or eliminate the colored races. In Africa the belief that family planning is a way of advocating genocide combines with the problem of lack of real experts in the field of family planning and of disproportionate allocation of funds to this area without regard to the goals of overall development. Additionally, some methods of fertility control are recommended by foreign "experts" which may be culturally unacceptable. In spite of these problems population programs are advancing in Africa. In order to be more readily acceptable, however, they will have to be considered within the global context of overall development, and they will have to be carried out largely by national personnel with international aid and international personnel remaining in the background.^ieng

Open letter to Pope John Paul II.

PIP: In an Open Letter to Pope John Paul II, written on World Population Day (July 11) 1991, Dr. Fred Sai, President of International Planned Parenthood Federation (IPPF), called for a dialogue on voluntary family planning as a means of avoiding unwanted pregnancy. A half million women die each year from pregnancy-related causes--a death toll that could be dramatically reduced by universal access to low cost, effective contraception. Family planning further represents the best protection against abortion. The Catholic Church's vehement opposition to abortion and family planning methods other than periodic abstinence is in marked contrast to its support to human rights in other settings. The Church has supported struggles for economic ju stice in and among nations, sided with the poor, and advocated for transitions to democracy. At the same time, the family planning movement--which has as its overall objective the protection of the health and welfare of women, children, and families--is viewed by the Vatican as a vehicle for the enslavement rather than liberation of women. The opening of a sensitive dialogue between the Catholic Church and supporters of voluntary family planning could help couples make sound moral decisions about their families and contribute to saving the lives of millions of women, most of them poor.^ieng

Building on the Cairo consensus.

PIP: No major disagreements developed between the North and the South at the 1994 International Conference on Population and Development (ICPD) because the conference preparatory process and the program of action recognized that population as a global problem is not mainly the concern of developing countries, but is instead an integral part of sustainable development and environmental problems. It was accepted early in the preparatory process that overconsumption, extravagant lifestyles, and excessive waste production in the wealthier northern countries contribute to global population and sustainable development problems as much as rapid population growth does in the poorer southern countries. However, political will to address these problems appears to be weak. While there has been no rush to develop population policies, efforts seem to have been stepped up to implement those already existing population policies and to accord population and family planning higher program priority. The author discusses the need to coordinate governmental and nongovernmental agencies in developing comprehensive reproductive health care programs, adolescent sexuality, female genital mutilation, unsafe abortion, maternal mortality, South-South cooperation, and the need for funding.^ieng

An overview of unsafe abortion in Africa. Foreword.

PIP: This overview of unsafe abortion in Africa indicates some reforms such as the provision of family planning services close to maternity units or hospitals where women can go for treatment of abortion. Medical students should learn how to perform a safe abortion and to manage incomplete abortions. Modern technology should be available for performing abortions. Abortion law should be examined from the medical and social perspective. The International Planned Parenthood Foundation's Strategic Plan, Vision 2000, in 1978, made the aforementioned recommendations and suggested that action be taken by family planning associations. This article refers to a number of studies that suggest a high rate of maternal mortality related to abortions performed under unsterile and unsafe conditions. Unsafe abortions may be performed by private doctors, traditional healers, or midwives. Unsafe practices include the insertion of IUDs or plastic cannulas or sticks and plants into the cervix. Women may resort to ingestion of unsafe products such as gasoline and other toxic substances in order to induce an abortion. Induced abortion rates among school girls is estimated to be high. There are health risks and health resources are strained from unsafe abortion. Most of the empirical studies of unsafe abortion are conducted in hospitals. Ironically, laws against abortion in Africa are the inheritance from colonial regimes that long ago abolished anti-abortion laws. The medical community is urged to respond with reason, moral sensibility, and social responsibility.^ieng

How family planning can save lives in Africa.

PIP: A pregnant woman in subSaharan Africa is 75 times more likely to die as a result of her pregnancy than a woman in western Europe. Most African doctors probably concentrate upon preventing and treating the medical causes of maternal mortality such as hemorrhage, toxemia, difficult and prolonged labor, incomplete abortion, and puerperal infection, but give less attention to non-medical factors such as multiparity, nutritional deficiencies, socioeconomic conditions, or whether women want children or not. Evidence from around the world shows that the risk of maternal or infant illness and death is highest in pregnancies before age 18 and after age 35 years, pregnancies after four births, and pregnancies spaced less than two years apart. Approximately 5.6 million infant deaths and 200,000 maternal deaths could thus be avoided annually if women chose to have their children within the safest years, with adequate spacing between births, and had completed families of moderate size. Good availability and use of effective and safe contraception could help reduce the number of women dying in childbirth from high-risk pregnancies and botched abortions. The author, president of the International Planned Parenthood Federation, urges doctors to promote family planning and recommends re-educating all health workers in family skills and the vital importance of contraceptive services for family health. The importance of reaching rural women and applying community-based distribution and social marketing approaches is stressed.^ieng

Political and economic factors influencing contraceptive uptake.

International, national and local level politics influence the uptake of contraception through consensuses, laws, financial and moral support or the creation of an enabling atmosphere. Opposition to contraception generally comes from some churches and groups opposed to particular technologies. Socio-economic factors, particularly education, the health care system and the perceived or actual cost of fertility regulation as compared to benefits expected from children also powerfully influence contraceptive use. For many poor women in developing countries their powerlessness in relation to their male partners is an important obstacle.

PIP: Recent estimates put the overall contraceptive prevalence rate (CPR) in less developed countries (LDCs) at over 50%, a 6-fold increase from a 1960 average of 9%. Thailand's rate of 10% in 1971 rose to 50% in 1979 and to 75% in 1992. China, Colombia, Mexico, and Mauritius also have had significant changes in their contraceptive profiles. The contraceptive revolution has been fostered by international agencies through various conferences: the 1965 UN Debate on the population problem, the 1968 Teheran Conference on Human rights, the 1974 and 1984 population conferences, and the 1975 and 1985 conferences on the International Decade of Women. Ardent feminists oppose the distribution of the injectables Depo-Provera and Norplant, while the US Food and Drug Administration requirements take more than 10 years for the development and testing of a contraceptive. The US's so-called Mexico City Policy stated that the US would not fund any organization that promoted abortion, and, thereby, it influenced the availability of contraceptives. The US managed to bring down its total fertility rate from 6.0 to 3.5 between 1842 and 1900. Indonesia achieved the same fertility decline between 1961 and 1984. Colombia, with much stronger programs and higher CPR, achieved it in 15 years, while Thailand, with a very comprehensive program, and China, with an even stronger one and an aggressive political leadership, achieved a similar rate of decline in 7 years. Higher gross national product is correlated to lower total fertility rate except for China, Sri Lanka, and Kerala in India. In communities where children contribute to the family economy, birth control tends to be regarded negatively; while in societies where the family contribution to the child's education is high, contraceptive use is also high. The cost of contraception includes the actual cost of the product, the cost of delivery, and travel costs and waiting time to the consumer.

Food, politics and population in Africa.

PIP: The food situation in Africa is discussed in light of the demographic realities of the region. The unique demographic situation of Africa, the continuing dependence of the region on grain imports, the low nutritional quality of food consumed over the greater part of the region, and the poor health conditions of most African children and mothers are underlined. The importance of the food situation to political stability is noted and the concern is expressed over the increasing time lag between the realization of the problem and action. The low priority given to Family Planning Programs is discussed. The urgency of increasing quality and quantity of food production in Africa and in particular the need for additional measures to decelerate the rate of population growth are underlined.^ieng

From Bucharest to Mexico.

PIP: There were marked differences between the views expressed at the 1974 Bucharest World Population Conference and those expressed at the 1984 Mexico City World Population Conference. At the 1974 conference there was considerable disagreement between delegates who emphasized the need to control population growth directly through the development of effective family planning policies and programs and other delegates who argued that a decline in fertility would occur automatically in response to vigorous development programs. By 1984 most participants had acquired a deeper understanding of the complex relationship between development and population growth, and most recognized the need to develop comprehensive family planning programs and policies. Ironically, the US, which in 1974 had taken a strong family planning stance, reversed its position, and in 1984 adovacated the less popular developmental approach. The 1974 participants did affirm that all couples and individuals had the right to freely limit and space their children, but the 1984 participants adopted specific recommendations to promote and strengthen family planning initiatives. They recommended that governments make all appropriate and medically approved family planning methods available to all couples and individuals, and especially to the most vulnerable and most difficult to reach segments of their populations, that governemnts ensure that all children have the opportunity to grow up in healthy and supportive environments, and that public and private organizations use their resources to help governments meet these goals. They further recommended that governments 1) improve the quality, effectiveness and safety of their family planning programs 2) utilize all appropriate and available channels to promote the delivery of family planning services, 3) provide family life, sex education, and appropriate family planning services for both male and female adolescents; 4) ensure that all couples and individuals have the right to freely and responsibly limit and space their children, and 5) refrain from using any family planning strategies which are coercive or discriminatory. The delegates also called on governments to translate family planning goals into specific policies and operational activities and to develop policies to help parents meet their child rearing responsibilities, to improve child welfare and child care services, to promote the establishment of adequate maternity and paternity leaves, and to help parents acquire suitable housing. Delegates also recognized the need to formulate development policies which supported each country's population policies, advocated upgrading the status of women, and dealt with the problem of maternal mortality. After considerable discussion, the participants recommended that abortion should not be promoted as a family planning method, but that women who have abortions should be treated humanely and provided with counseling. Many delegates from the developing countries criticized the conference for failing to deal adequately with the issue of funding. Many countries lack the resources needed to implement the conference's recommendations.^ieng