Maternal serum alpha-fetoprotein screening: report of a Canadian pilot project.

A pilot project of maternal serum alpha-fetoprotein (MSAFP) screening was carried out in Ontario from 1982 to 1985 to examine the feasibility and acceptability of screening a prenatal population for open fetal neural tube defects. A total of 8140 patients at low genetic risk were screened. Patient acceptance was excellent. Blood samples were taken at 16 to 18 weeks'' gestation. If the MSAFP level was elevated, the assay was repeated and an ultrasound examination performed. Amniocentesis was offered to 67 women with unexplained persistently elevated levels. The outcome of pregnancy was known in 7473 patients (91.8%). Seven of nine known open fetal neural tube defects were detected. All were confirmed, and no unaffected fetuses were aborted on the basis of the screening results. The rates of perinatal death (6.7%), intrauterine growth retardation (11.7%) and prematurity (23.3%) were significantly higher among the patients with unexplained elevated MSAFP levels than among those with normal levels (p less than 0.001). Of 20 patients with unexplained low levels, 10 subsequently had spontaneous abortions and 10 gave birth to term appropriate-for-gestational-age infants. Seven of nine patients who gave birth to infants with autosomal trisomy had MSAFP values below the median. The findings indicate that MSAFP screening is feasible, accurate and acceptable in a low-risk area.     

The C677T methylenetetrahydrofolate reductase variant and third trimester obstetrical complications in women with unexplained elevations of maternal serum alpha-fetoprotein

Introduction

The C677T MTHFR variant has been associated with the same third trimester pregnancy complications as seen in women who have elevations of maternal serum α-fetoprotein (MSAFP). We hypothesized that these women with third trimester pregnancy complications and MSAFP elevations would have an increased frequency of the variant compared to an abnormal study control group (women with MSAFP elevations without pregnancy complications) as well as to normal population controls.

Methods

Women who had unexplained elevations of MSAFP in pregnancy were ascertained retrospectively. The frequency of the C677T MTHFR variant among those women with unexplained elevations of MSAFP who had experienced later pregnancy complications was compared to that of women with unexplained elevations of MSAFP without complications as well as to that of the previously established Manitoba frequency.

Results

Women who had complications of pregnancy and an unexplained MSAFP elevation had a higher allele frequency for the C677T MTHFR variant (q = 0.36,) compared to women with MSAFP elevations and normal pregnancy outcomes (q = 0.25, OR 1.73 95% CI 1.25–2.37, p = 0.03). The frequency was also higher than that of the population controls (q= 0.25, OR 1.70 95% CI 1.11–2.60, p = 0.007). The frequency in women with MSAFP elevations without pregnancy complications was not significantly different from that of the population controls (p = 0.41).

Conclusion

Women with unexplained elevations of MSAFP and who experience complications in later pregnancy are more likely to have one or two alleles of the C677T MTHFR variant.

     

Variability in predicted rates of Down syndrome associated with elevated maternal serum alpha-fetoprotein levels in older women.

Quantitative predictions of rates of Down syndrome offspring as a function of maternal serum alpha-fetoprotein (MSAFP) values and of maternal age were reviewed. Comparisons were made of 35-year-equivalent-risk values by maternal age, that is, MSAFP values (at various maternal ages) that predict the risk (of a Down syndrome offspring) equivalent to that of an average 35-year-old woman irrespective of knowledge of MSAFP. This boundary was chosen because MSAFP values that predict a greater risk than this point for younger women or a lower risk for older women are likely in many jurisdictions to alter a decision about amniocentesis that would be reached without knowledge of MSAFP. There were marked differences among available studies in these 35-year-equivalent-risk values for older women. For instance, for age 41, the values among studies vary from 1.5 MoM to 2.1 MoM and the predicted proportion of 41-year-old women likely to be affected clinically by MSAFP determinations by the above criterion is 4.4%-18%, depending on which rate schedule is used. At age 39, the variation is 1.1 to 1.9 MoM or 7.1% to 38%. Possible explanations for the variation include sampling fluctuation. Relatively few data on Down syndrome have been used to calculate the parameters of the gaussian distributions used by the studies reviewed. It is suggested that great caution be used before employing published rate schedules for genetic counseling of older women, at least until sufficient data are collected and the nature of the discrepancies among studies is clarified.     

All MoMs are not equal: some statistical properties associated with reporting results in the form of multiples of the median.

The statistical procedure for discriminating between a Down syndrome or neural tube defect (NTD) fetus and a normal fetus relies, to a great extent, on the reporting of maternal serum alpha-fetoprotein (MSAFP), hCG, and uE3 results in the form of multiples of the median (MoMs). Further, threshold MoMs values for MSAFP, such as 2.5 MoMs, are often used to define a reference range to identify an NTD fetus. We show that a constant threshold-MoMs cutoff for MSAFP values actually refers to different percentiles of MSAFP levels at different gestational ages and that the combining of MoMs values between centers and gestational ages, such as suggested by Wald et al. for deriving a patient-specific risk index, is highly questionable. The results presented in this paper are quite general and will apply to all situations where MoMs are used.     

生态治理政策工具对农户行为的影响差异研究——以宁夏盐池县为例

政策工具被认为是政府为解决某个公共问题采取的具体手段或措施,一项政策可以视作目标和多种政策工具的组合。在生态治理过程中,不同政策工具对农户行为的刺激程度不同,进而导致不同的政策效果。分离不同政策工具的影响,可为工具选择和政策优化提供科学参考。以盐池县为例,利用基于该县1983-2017年内出台的316份生态政策文本构建的政策工具数据集和VAR模型中的脉冲响应和方差分解方法定量研究了强制型、混合型和自愿型三大类政策工具及十种子工具对农户耕作、放牧、造林3种行为的影响。结果表明：（1）政策工具对农户行为的影响具有时效性,一般在政策出台后2-3年内影响最大,随后逐渐减小并消失,影响持续时间为7-10年。（2）总体来看,政策工具对农户行为的冲击力度较小,冲击范围在0-0.30之间,说明农户行为还受到其他诸多因素的影响。（3）10年累计影响从大到小依次为强制型、混合型、自愿型,其中直接提供和规制两种子工具的影响最大。放牧行为受到政策工具的刺激最大,耕作行为次之,造林行为最小。（4）直接提供工具对耕作行为具有最大正向影响,最大冲击为0.30;规制工具在短期内抑制牲畜数量增长,而直接提供和补贴工具促进牲畜数量增长,且由于冲击曲线存在正负波动,说明政府与农户在牲畜养殖上存在长期博弈;只有规制工具对造林行为具有积极影响,说明造林更多是在政府的主导下进行。建议充分利用政策工具的短期效应,凸显政府角色,及时做好政策效果评估工作,调整工具组合,助力生态目标的实现。     

Male versus female genital alteration: Differences in legal,medical, and socioethical responses

The different legal, social, and medical approaches to ritually based male and female genital circumcision in the United States are highlighted in this article. The religious and historical origins of these practices are briefly examined, as well as the effect of changing policy statements by American medical associations on the number of circumcisions performed. Currently, no state or federal laws single out male circumcision for regulation. The tolerant attitudes toward male circumcision in law, medicine, and societal opinion stand in striking contrast to the attitudes of those disciplines toward even the least invasive form of female genital alteration. US law tacitly condones male circumcision by providing exemptions that are not available for other medical procedures, while criminalizing any similar or even less extensive procedure on females. The increase in immigration, over the past few decades, of people from countries in which female genital alteration is a cultural tradition has brought the issue to the United States. The medical profession's changing approach over time toward male circumcision is primarily responsible for such different legal and societal reactions toward female genital alteration.     

Level of alpha-fetoprotein in maternal serum before and after chorionic villus sampling

To evaluate incidence and severity of feto-maternal transfusion post-chorionic villus sampling (CVS), maternal serum AFP (MSAFP) were determined for 88 patients before and 15 minutes after CVS. To know whether MSAFP elevation could have clinical implications, a questionnaire was sent to the patients researching if they have had haemorrhages, temperature, spontaneous abortion or premature delivery in the period post CVS. Results of the present study indicate that 44.7% of patients present MSAFP significative elevation (greater than or equal to 8 micrograms/l), a variable elevation (from 8 to 423 micrograms/l). There is no relation between MSAFP elevation and unfavourable events post CVS.     

Guidelines for the Retention,Storage, and Use of Residual Dried Blood Spot Samples after Newborn Screening Analysis: Statement of the Council of Regional Networks for Genetic Services

These guidelines provide scientific information for policy development by state health departments considering appropriate use of newborn screening specimens after screening tests are finished. Information was collected, debated, and formulated into a policy statement by the Newborn Screening Committee of the Council of Regional Networks for Genetic Services (CORN), a federally funded national consortium of representatives from 10 regional genetics networks. Newborn screening programs vary widely in approaches and policies concerning residual dried blood spot samples (DBS) collected for newborn screening. Recognition of the epidemiological utility of DBS samples for HIV seroprevalence surveys and a growing interest in DBSs for DNA analysis has intensified consideration of issues regarding retention, storage, and use of residual DBS samples. Potentially these samples provide a genetic material “bank” for all newborns nationwide. Their value as a resource for other uses has already been recognized by scientists, administrators, and judicial officials. Programs should promulgate rules for retention and use of residual newborn screening DBS samples based on scientifically valid information. Banking of newborn samples as sources of genetic material should be considered in light of potential benefit or harm to society.     

Effectiveness of the public health policy for breast cancer screening in Finland: population based cohort study.

OBJECTIVE: To evaluate the effectiveness of screening for breast cancer as a public health policy. DESIGN: Follow up in 1987-92 of Finnish women invited to join the screening programme in 1987-9 and of the control women (balanced by age and matched by municipality of residence), who were not invited to the service screening. SETTING: Finland. SUBJECTS: Of the Finnish women born in 1927-39, 89893 women invited for screening and 68862 controls were followed; 1584 breast cancers were diagnosed. MAIN OUTCOME MEASURES: Rate ratio of deaths from breast cancer among the women invited for screening to deaths among those not invited. RESULTS: There were 385 deaths from breast cancer, of which 127 were among the 1584 incident cases in 1987-92. The rate ratio of death was 0.76 (95% confidence interval 0.53 to 1.09). The effect was larger and significant (0.56; 0.33 to 0.95) among women aged under 56 years at entry. 20 cancers were prevented (one death prevented per 10000 screens). CONCLUSIONS: A breast screening programme can achieve a similar effect on mortality as achieved by the trials for breast cancer screening. However, it may be difficult to justify a screening programme as a public health policy on the basis of the mortality reduction only. Whether to run a screening programme as a public health policy also depends on its effects on the quality of life of the target population and what the resources would be used for if screening was not done. Given all the different dimensions in the effect, mammography based breast screening is probably justifiable as a public health policy.     

The state,housing policy and Afro‐Caribbean migration to France

France's Afro‐Caribbean population forms a distinctive element in postwar migrant labour recruitment: of French nationality, with an equal balance of men and women, and strongly concentrated in public sector employment, especially in the Paris region. State policy strongly influenced the migration flow from the Caribbean islands, especially from the early 1960s. This article looks at aspects of the migrants’ housing experience, using aggregate statistics to establish general tenure patterns and interviews to recreate biographical histories. Afro‐Caribbean migrants avoided for the most part the worst excesses of the housing crisis of the 1960s and 1970s, though housing conditions ‐ especially for newly‐arriving migrants ‐ were frequently poor. Access to the public housing sector is shown to be crucial, though the role of the state was less direct (specifically aimed at the Caribbean population through the migration agency) than indirect (through the role of employers and the general involvement of the state in housing provision).     

Regulation to Create Environments Conducive to Physical Activity: Understanding the Barriers and Facilitators at the Australian State Government Level

Introduction

Policy and regulatory interventions aimed at creating environments more conducive to physical activity (PA) are an important component of strategies to improve population levels of PA. However, many potentially effective policies are not being broadly implemented. This study sought to identify potential policy/regulatory interventions targeting PA environments, and barriers/facilitators to their implementation at the Australian state/territory government level.

Methods

In-depth interviews were conducted with senior representatives from state/territory governments, statutory authorities and non-government organisations (n = 40) to examine participants'': 1) suggestions for regulatory interventions to create environments more conducive to PA; 2) support for preselected regulatory interventions derived from a literature review. Thematic and constant comparative analyses were conducted.

Results

Policy interventions most commonly suggested by participants fell into two areas: 1) urban planning and provision of infrastructure to promote active travel; 2) discouraging the use of private motorised vehicles. Of the eleven preselected interventions presented to participants, interventions relating to walkability/cycling and PA facilities received greatest support. Interventions involving subsidisation (of public transport, PA-equipment) and the provision of more public transport infrastructure received least support. These were perceived as not economically viable or unlikely to increase PA levels. Dominant barriers were: the powerful ‘road lobby’, weaknesses in the planning system and the cost of potential interventions. Facilitators were: the provision of evidence, collaboration across sectors, and synergies with climate change/environment agendas.

Conclusion

This study points to how difficult it will be to achieve policy change when there is a powerful ‘road lobby’ and government investment prioritises road infrastructure over PA-promoting infrastructure. It highlights the pivotal role of the planning and transport sectors in implementing PA-promoting policy, however suggests the need for clearer guidelines and responsibilities for state and local government levels in these areas. Health outcomes need to be given more direct consideration and greater priority within non-health sectors.     

Marine ecosystem regime shifts: challenges and opportunities for ecosystem-based management

Regime shifts have been observed in marine ecosystems around the globe. These phenomena can result in dramatic changes in the provision of ecosystem services to coastal communities. Accounting for regime shifts in management clearly requires integrative, ecosystem-based management (EBM) approaches. EBM has emerged as an accepted paradigm for ocean management worldwide, yet, despite the rapid and intense development of EBM theory, implementation has languished, and many implemented or proposed EBM schemes largely ignore the special characteristics of regime shifts. Here, we first explore key aspects of regime shifts that are of critical importance to EBM, and then suggest how regime shifts can be better incorporated into EBM using the concept of integrated ecosystem assessment (IEA). An IEA uses approaches that determine the likelihood that ecological or socio-economic properties of systems will move beyond or return to acceptable bounds as defined by resource managers and policy makers. We suggest an approach for implementing IEAs for cases of regime shifts where the objectives are either avoiding an undesired state or returning to a desired condition. We discuss the suitability and short-comings of methods summarizing the status of ecosystem components, screening and prioritizing potential risks, and evaluating alternative management strategies. IEAs are evolving as an EBM approach that can address regime shifts; however, advances in statistical, analytical and simulation modelling are needed before IEAs can robustly inform tactical management in systems characterized by regime shifts.     

Commons and anticommons in a simple renewable resource harvest model

We consider a model where agents harvesting from a renewable resource can impose limitations on the harvesting efforts of other agents. Obstructing the harvesting of others comes at a cost, and is viewed as regulation of resource access. Thus, the agent population comprises agents that do not obstruct (“cooperators”) and agents that obstruct (“obstructors”). As the economically better performing strategy spreads in the population, the system self-organizes at a level of obstruction which depends on the costs of obstruction, the obstruction efficiency and the history of the system. We show that commons and anticommons can be considered as the end points of a continuum of varying degrees of obstruction and we identify three regimes for the stationary state of the evolution dynamics: (i) a state where the system ends up in a tragedy of the commons, (ii) a tragedy of the anticommons state and (iii) a moderately regulated state in between both extremes. The more a policy environment in the moderately regulated state is tuned for optimality, the higher the danger that a fluctuation destabilizes the system into severe overexploitation.     

The Agency of Welfare Workers: Negotiating Devolution, Privatization, and the Meaning of Self-Sufficiency

In this article I examine how the neoliberal agenda of downsizing the state and minimizing its role in regulating the market has shaped welfare policy and the work of welfare provision. Using a study of welfare reform in Oregon, I explore how the enactment of welfare-to-work policies positions workers to negotiate the ideological terrain of welfare reform and the conflicts that privatization and devolution generate in a social welfare context. Self-sufficiency, the professed goal of welfareto- work programs, is a complex concept, saturated with ideological meaning. Examination of the work of welfare provision provides an opportunity to analyze how workers give meaning to self-sufficiency and construct their work as positive for the families they serve. However, high caseloads, unrealistic agency expectations, and conflicting mandates bear down hard on workers, creating disenchantment with agency policy and undermining workers' ability to meet clients' needs, [welfare, ideology, work, the United States, neoliberalism]     

The role of post-translational modifications in the regulation of MCL1

Apoptosis is an evolutionarily conserved form of programed cell death (PCD) that has a vital effect on early embryonic development, tissue homeostasis and clearance of damaged cells. Dysregulation of apoptosis can lead to many diseases, such as Alzheimer's disease, cancer, AIDS and heart disease. The anti-apoptotic protein MCL1, a member of the BCL2 family, plays important roles in these physiological and pathological processes. Its high expression is closely related to drug resistances in the treatment of tumor. This review summarizes the structure and function of MCL1, the types of post-translational modifications of MCL1 and their effects on the functions of MCL1, as well as the treatment strategies targeting MCL1 in cancer therapy. The research on the fine regulation of MCL1 will be favorable to the provision of a promising future for the design and screening of MCL1 inhibitors.     

Community care for the elderly 1976-84.

The aging of the elderly population is of crucial importance as people who are over 80 make far greater use of health and social services than any other age group. Government guidelines on the provision of services, which are generally related to the whole population aged 65 and over, fail to take account of this change in the age structure of the elderly population and are no longer appropriate. Recent trends in the provision of domiciliary services, day care, specialist housing for the elderly, and residential care have been related to changes in the number of potential consumers. Ironically, despite the government''s stated commitment to "community care," the chief growth area has been private institutional care. The number of day care places and sheltered housing units has also increased in real terms, but the provision of domiciliary services, such as home help and health visitor visits to the elderly, has either fallen behind or barely matched the increase in the number of very old people. If community care is to be made a reality and if the present inadequate levels of service are to be maintained, let alone improved, then additional resources, greater cooperation among agencies, and a more imaginative approach to the development and delivery of services are urgently needed.     

Multiple ecosystem services and disservices of the urban forest establishing their connections with landscape structure and sociodemographics

The promotion of sustainable cities is critical under future environmental change and population growth. Cities in the present and future can ensure the provision of ecosystem services to their urban inhabitants. The urban forest is one of the main suppliers of ecosystem services in urban areas, and can provide the base information to quantify ecosystem services and disservices, detecting the areas were low provision of those occur. In this study multiple ecosystem services and disservices were quantified using transferable indicators in order to detect areas for environmental improvement. The set of spatially explicit indicators enables the detection of areas of low and high provision of ecosystem services. The analysis showed synergies existing among regulating, provisioning and supporting services, while trade-offs were found with cultural services and regulating, provisioning and supporting services. Ecosystem services provision was positively related to the amount of vegetation and negatively related to its degree of fragmentation. A high provision of ecosystem services was found in less populated areas, with more educated and affluent people, highlighting the strong relations existing between social vulnerabilities and areas of low provision of services. Results from this research provide insights on the role of policy makers on better distributed supply of ecosystem services and on how the landscape structure can be modified to plan for sustainable cities.     

Addressing consumer grievances in medicine: policies and practices of newborn screening programs in the United States

Newborn screening programs collectively administer the largest genetic testing initiative in the United States. The redress of grievances is an important mechanism for consumers to provide input into clinical and public health programs. In this study, we evaluated mechanisms for addressing consumer grievances in newborn screening programs. To do this, we surveyed all 50 state plus the District of Columbia newborn screening programs by questionnaire regarding protocols for receipt and redress of problems reported by parents of newborns and ascertained the existence and nature of complaints and how complaints were documented and addressed. Pertinent state and federal legislation and regulation were also reviewed. Six of 49 newborn screening programs reported having formal policies for handling consumer grievances. Four states reported having pertinent legislation or regulation. Thirty-eight of 49 states reported having received complaints from 1993 to 1995. Thirteen of 49 newborn screening programs reported that they actively seek feedback from consumers. Consumer grievances ranged from minor complaints to potentially life-threatening concerns. In general, complaints are managed on an ad hoc basis; formal policies are typically lacking. As newborn screening programs affect a vast number of Americans, a proactive and comprehensive approach, including solicitation of consumer feedback, could benefit both newborn screening programs and the public served by them.     

On the Three-Taxon Approach to Parsimony Analysis

The following three basic defects for which three-taxon analysis has been rejected as a method for biological systematics are reviewed: (1) character evolution is a priori assumed to be irreversible; (2) basic statements that are not logically independent are treated as if they are; (3) three-taxon statements that are considered as independent support for a given tree may be mutually exclusive on that tree. It is argued that these criticisms only relate to the particular way the three-taxon approach was originally implemented. Four-taxon analysis, an alternative implementation that circumvents these problems, is derived. Four-taxon analysis is identical to standard parsimony analysis except for an unnatural restriction on the maximum amount of homoplasy that may be concentrated in a single character state. This restriction follows directly from the basic tenet of the three-taxon approach, that character state distributions should be decomposed into basic statements that are, in themselves, still informative with respect to relationships. A reconsideration of what constitutes an elementary relevant statement in systematics leads to a reformulation of standard parsimony as two-taxon analysis and to a rejection of four-taxon analysis as a method for biological systematics.     

Nutrient‐specific foraging leads to Allee effects and dynamic functional responses

Most animals forage in nutritionally complicated environments in which the densities of complementary foods vary in space and time. Locally rare foods can lead to nutritional deficiencies in consumers, yet there has been little consideration of the influence of nutritional deficits, and consumers’ efforts to redress these deficits, on population and community dynamics. A taxonomically and trophically diverse group of animals can redress accumulated deficits using nutrient‐specific foraging, defined here as the ability of an animal to bias its foraging effort towards certain foods on the basis of its own nutritional state. We focus on the true omnivores, because they feed on vastly different nutrient sources, animals and plants. We use an ordinary differential equation model to show that nutrient‐specific foraging may destabilize omnivore–prey population dynamics, depending on the degree to which the omnivore alters its foraging in an attempt to balance its nutritional state. In particular, a high behavioral sensitivity to nutritional imbalances led to a novel type of Allee effect driven by the interaction between prey density and nutritional deficiencies in the omnivore. Our model overall is characterized by a causal loop between the omnivore's nutritional state, food preferences and population dynamics. Consequently, the omnivore exhibited a dynamic functional response, in which the relationship between prey density and omnivore per capita consumption of prey was influenced by the current nutritional state of the omnivore. With regards to omnivory in general, our results reinforce the idea that statements about the effects of omnivory on population or community stability are not possible without a consideration of the behavioral mechanisms of diet mixing.