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Abstract Background Whilst schools provide a potentially appropriate setting for preventing substance use among young people, systematic review evidence suggests that past interventions in this setting have demonstrated limited effectiveness in preventing tobacco, alcohol and other drug use. Interventions that adopt a mental wellbeing approach to prevent substance use offer considerable promise and resilience theory provides one method to impact on adolescent mental well-being. The aim of the proposed study is to examine the efficacy of a resilience intervention in decreasing the tobacco, alcohol and illicit drug use of adolescents. Methods A cluster randomised controlled trial with schools as the unit of randomisation will be undertaken. Thirty two schools in disadvantaged areas will be allocated to either an intervention or a control group. A comprehensive resilience intervention will be implemented, inclusive of explicit program adoption strategies. Baseline surveys will be conducted with students in Grade 7 in both groups and again three years later when the student cohort is in Grade 10. The primary outcome measures will include self-reported tobacco, alcohol, marijuana and other illicit drug use. Comparisons will be made post-test between Grade 10 students in intervention and control schools to determine intervention effectiveness across all measures. Discussion To the authors’ knowledge this is the first randomised controlled trial to evaluate the effectiveness of a comprehensive school-based resilience intervention, inclusive of explicit adoption strategies, in decreasing tobacco, alcohol and illicit drug use of adolescents attending disadvantaged secondary schools. Trial registration ACTRN12611000606987

Abstract Background The rise of the internet and related technologies has significant implications for the treatment of complex health problems, including the combination of depression and alcohol/other drug (AOD) misuse. To date, no research exists to test the real world uptake of internet and computer-delivered treatment programs in clinical practice. This study is important, as it is the first to examine the adoption of the SHADE treatment program, a DVD-based psychological treatment for depression and AOD use comorbidity, by clinicians working in a publicly-funded AOD clinical service. The study protocol that follows describes the methodology of this dissemination trial. Methods/design 19 clinicians within an AOD service on the Central Coast of New South Wales, Australia, will be recruited to the trial. Consenting clinicians will participate in a baseline focus group discussion designed to explore their experiences and perceived barriers to adopting innovation in their clinical practice. Computer comfort and openness to innovation will also be assessed. Throughout the trial, current, new and wait-list clients will be referred to the research program via the clinical service, which will involve clients completing a baseline and 15-week follow-up clinical assessment with independent research assistants, comprising a range of mental health and AOD measures. Clinicians will also complete session checklists following each clinical session with a client, outlining the extent to which the SHADE computer program was used. Therapeutic alliance will be measured at intake and discharge from both the clinician and client perspectives. Discussion This study will provide comprehensive data on the factors associated with the adoption of an innovative, computer-delivered evidence-based treatment program, SHADE, by clinicians working in an AOD service. The results will contribute to the development of a model of dissemination of SHADE, which could be applied to a range of technological innovations. Clinical trials registry Australian Clinical Trial Registration Number: ACTRN12611000382976.

Abstract Background The primary behavioural risks for the most common causes of mortality and morbidity in developed countries are tobacco smoking, poor nutrition, risky alcohol use, and physical inactivity. Evidence, guidelines and policies support routine clinician delivery of care to prevent these risks within primary care settings. Despite the potential afforded by community health services for the delivery of such preventive care, the limited evidence available suggests it is provided at suboptimal levels. This study aims to assess the effectiveness of a multi-strategic practice change intervention in increasing clinician's routine provision of preventive care across a network of community health services. Methods/Design A multiple baseline study will be conducted involving all 56 community health facilities in a single health district in New South Wales, Australia. The facilities will be allocated to one of three administratively-defined groups. A 12 month practice change intervention will be implemented in all facilities in each group to facilitate clinician risk assessment of eligible clients, and clinician provision of brief advice and referral to those identified as being 'at risk'. The intervention will be implemented in a non-random sequence across the three facility groups. Repeated, cross-sectional measurement of clinician provision of preventive care for four individual risks (smoking, poor nutrition, risky alcohol use, and physical inactivity) will occur continuously for all three facility groups for 54 months via telephone interviews. The interviews will be conducted with randomly selected clients who have visited a community health facility in the last two weeks. Data collection will commence 12 months prior to the implementation of the intervention in the first group, and continue for six months following the completion of the intervention in the last group. As a secondary source of data, telephone interviews will be undertaken prior to and following the intervention with randomly selected samples of clinicians from each facility group to assess the reported provision of preventive care, and the acceptability of the practice change intervention and implementation. Discussion The study will provide novel evidence regarding the ability to increase clinician's routine provision of preventive care across a network of community health facilities. Trial registration Australian Clinical Trials Registry ACTRN12611001284954 Universal Trial Number (UTN) U1111-1126-3465

Abstract Background Despite schools theoretically being an ideal setting for accessing adolescents and preventing initiation of substance use, there is limited evidence of effective interventions in this setting. Resilience theory provides one approach to achieving such an outcome through improving adolescent mental well-being and resilience. A study was undertaken to examine the potential effectiveness of such an intervention approach in improving adolescent resilience and protective factor scores; and reducing the prevalence of adolescent tobacco, alcohol and marijuana use in three high schools. Methods A non-controlled before and after study was undertaken. Data regarding student resilience and protective factors, and measures of tobacco, alcohol and marijuana use were collected from grade 7 to 10 students at baseline (n = 1449) and one year following a three year intervention (n = 1205). Results Significantly higher resilience and protective factors scores, and significantly lower prevalence of substance use were evident at follow up. Conclusions The results suggest that the intervention has the potential to increase resilience and protective factors, and to decrease the use of tobacco, alcohol and marijuana by adolescents. Further more rigorous research is required to confirm this potential.

Abstract Background Mental health inpatients smoke at higher rates than the general population and are disproportionately affected by tobacco dependence. Despite the advent of smoke free policies within mental health hospitals, limited systems are in place to support a cessation attempt post hospitalisation, and international evidence suggests that most smokers return to pre-admission smoking levels following discharge. This protocol describes a randomised controlled trial that will test the feasibility, acceptability and efficacy of linking inpatient smoking care with ongoing community cessation support for smokers with a mental illness. Methods/Design This study will be conducted as a randomised controlled trial. 200 smokers with an acute mental illness will be recruited from a large inpatient mental health facility. Participants will complete a baseline survey and will be randomised to either a multimodal smoking cessation intervention or provided with hospital smoking care only. Randomisation will be stratified by diagnosis (psychotic, non-psychotic). Intervention participants will be provided with a brief motivational interview in the inpatient setting and options of ongoing smoking cessation support post discharge: nicotine replacement therapy (NRT); referral to Quitline; smoking cessation groups; and fortnightly telephone support. Outcome data, including cigarettes smoked per day, quit attempts, and self-reported 7-day point prevalence abstinence (validated by exhaled carbon monoxide), will be collected via blind interview at one week, two months, four months and six months post discharge. Process information will also be collected, including the use of cessation supports and cost of the intervention. Discussion This study will provide comprehensive data on the potential of an integrated, multimodal smoking cessation intervention for persons with an acute mental illness, linking inpatient with community cessation support. Trial Registration Australian and New Zealand Clinical Trials Registry ANZTCN: ACTRN12609000465257

Abstract Background Despite the need for a reduction in levels of childhood exposure to environmental tobacco smoke (ETS) being a recognised public health goal, the delivery of ETS preventive care in child health service settings remains a largely unstudied area. The purpose of this study was to determine the prevalence of ETS preventive care in child health services; differences in the provision of care by type of service; the prevalence of strategies to support such care; and the association between care support strategies and care provision. Method One-hundred and fifty-one (83%) child health service managers within New South Wales, Australia completed a questionnaire in 2002 regarding the: assessment of parental smoking and child ETS exposure; the provision of parental smoking cessation and ETS-exposure reduction advice; and strategies used to support the provision of such care. Child health services were categorised based on their size and case-mix, and a chi-square analysis was performed to compare the prevalence of ETS risk assessment and ETS prevention advice between service types. Logistic regression analysis was used to examine associations between the existence of care support strategies and the provision of ETS risk assessment and ETS exposure prevention advice. Results A significant proportion of services reported that they did not assess parental smoking status (26%), and reported that they did not assess the ETS exposure (78%) of any child. Forty four percent of services reported that they did not provide smoking cessation advice and 20% reported they did not provide ETS exposure prevention advice. Community based child and family health services reported a greater prevalence of ETS preventive care compared to other hospital based units. Less than half of the services reported having strategies to support the provision of ETS preventive care. The existence of such support strategies was associated with greater odds of care provision. Conclusions The existence of major gaps in recommended ETS preventive care provision suggests a need for additional initiatives to increase such care delivery. The low prevalence of strategies that support such care delivery suggests a potential avenue to achieve this outcome.

Abstract Background The introduction of total smoking bans represents an important step in addressing the smoking and physical health of people with mental illness. Despite evidence indicating the importance of staff support in the successful implementation of smoking bans, limited research has examined levels of staff support prior to the implementation of a ban in psychiatric settings, or factors that are associated with such support. This study aimed to examine the views of psychiatric inpatient hospital staff regarding the perceived benefits of and barriers to implementation of a successful total smoking ban in mental health services. Secondly, to examine the level of support among clinical and non-clinical staff for a total smoking ban. Thirdly, to examine the association between the benefits and barriers perceived by clinicians and their support for a total smoking ban in their unit. Methods Cross-sectional survey of both clinical and non-clinical staff in a large inpatient psychiatric hospital immediately prior to the implementation of a total smoking ban. Results Of the 300 staff, 183 (61%) responded. Seventy-three (41%) of total respondents were clinical staff, and 110 (92%) were non-clinical staff. More than two-thirds of staff agreed that a smoking ban would improve their work environment and conditions, help staff to stop smoking and improve patients' physical health. The most prevalent clinician perceived barriers to a successful total smoking ban related to fear of patient aggression (89%) and patient non-compliance (72%). Two thirds (67%) of all staff indicated support for a total smoking ban in mental health facilities generally, and a majority (54%) of clinical staff expressed support for a ban within their unit. Clinical staff who believed a smoking ban would help patients to stop smoking were more likely to support a smoking ban in their unit. Conclusions There is a clear need to more effectively communicate to staff the evidence that consistently applied smoking bans do not increase patient aggression. There is also a need to communicate the benefits of smoking bans in aiding the delivery of smoking cessation care, and the benefits of both smoking bans and such care in aiding patients to stop smoking.

Abstract Background Inadequate fruit and vegetable consumption in childhood increases the risk of developing chronic disease. Despite this, a substantial proportion of children in developed nations, including Australia, do not consume sufficient quantities of fruits and vegetables. Parents are influential in the development of dietary habits of young children but often lack the necessary knowledge and skills to promote healthy eating in their children. The aim of this study is to assess the efficacy of a telephone-based intervention for parents to increase the fruit and vegetable consumption of their 3- to 5-year-old children. Methods/Design The study, conducted in the Hunter region of New South Wales, Australia, employs a cluster randomised controlled trial design. Two hundred parents from 15 randomly selected preschools will be randomised to receive the intervention, which consists of print resources and four weekly 30-minute telephone support calls delivered by trained telephone interviewers. The calls will assist parents to increase the availability and accessibility of fruit and vegetables in the home, create supportive family eating routines and role-model fruit and vegetable consumption. A further two hundred parents will be randomly allocated to the control group and will receive printed nutrition information only. The primary outcome of the trial will be the change in the child's consumption of fruit and vegetables as measured by the fruit and vegetable subscale of the Children's Dietary Questionnaire. Pre-intervention and post-intervention parent surveys will be administered over the telephone. Baseline surveys will occur one to two weeks prior to intervention delivery, with follow-up data collection calls occurring two, six, 12 and 18 months following baseline data collection. Discussion If effective, this telephone-based intervention may represent a promising public health strategy to increase fruit and vegetable consumption in childhood and reduce the risk of subsequent chronic disease. Trial registration Australian Clinical Trials Registry ACTRN12609000820202

A gold nanoparticle platform is described in which post-synthesis surface modifications can be conducted using kinetically-tunable strain-promoted cycloaddition chemistry, which is dependent on the electronic properties of the complementary dipolar species. This permits chemoselective reactivity with one reactive dipole over another less reactive dipole, providing exciting opportinities for kinetically-directed self-sorting strategies.

Sustained attention (SA) and working memory (WM) are critical processes, but the brain networks supporting these abilities in development are unknown. We characterized the functional brain architecture of SA and WM in 9- to 11-year-old children and adults. First, we found that adult network predictors of SA generalized to predict individual differences and fluctuations in SA in youth. A WM model predicted WM performance both across and within children-and captured individual differences in later recognition memory-but underperformed in youth relative to adults. We next characterized functional connections differentially related to SA and WM in youth compared to adults. Results revealed 2 network configurations: a dominant architecture predicting performance in both age groups and a secondary architecture, more prominent for WM than SA, predicting performance in each age group differently. Thus, functional connectivity (FC) predicts SA and WM in youth, with networks predicting WM performance differing more between youths and adults than those predicting SA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kardan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Municipal wastewater treatment plant (WWTP) effluents are a ubiquitous source of contamination whose impacts on fish and other aquatic organisms span across multiple levels of biological organization. Despite this, few studies have addressed the impacts of WWTP effluents on fish communities, especially during the winter-a season seldom studied. Here, we assessed the impacts of wastewater on fish community compositions and various water quality parameters during the summer and winter along two effluent gradients in Hamilton Harbour, an International Joint Commission Area of Concern in Hamilton, Canada. We found that fish abundance, species richness, and species diversity were generally highest in sites closest to the WWTP outfalls, but only significantly so in the winter. Fish community compositions differed greatly along the effluent gradients, with sites closest and farthest from the outfalls being the most dissimilar. Furthermore, the concentrations of numerous contaminants of emerging concern (CECs) in the final treated effluent were highest during the winter. Water quality of sites closer to the outfalls was poorer than at sites farther away, especially during the winter. We also demonstrated that WWTPs can significantly alter the thermal profile of effluent-receiving environments, increasing temperature by as much as ~9 °C during the winter. Our results suggest that wastewater plumes may act as ecological traps in winter, whereby fish are attracted to the favourable temperatures near WWTPs and are thus exposed to higher concentrations of CECs. This study highlights the importance of winter research as a key predictor in further understanding the impacts of wastewater contamination in aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although effluent from municipal wastewater treatment plants (WWTPs) is a major stressor in receiving environments, relatively few studies have addressed how its discharge affects natural fish communities. Here, we assessed fish community composition over three years along a gradient of effluent exposure from two distinct WWTPs within an International Joint Commission Area of Concern on the Great Lakes (Hamilton Harbour, Canada). We found that fish communities changed with distance from both WWTPs, and were highly dissimilar between sites that were closest to and furthest from the wastewater outfall. Despite differences in the size and treatment technology of the WWTPs and receiving habitats downstream, we found that the sites nearest the outfalls had the highest fish abundances and contained a common set of signature fish species (i.e., round goby Neogobius melanostomus, green sunfish Lepomis cyanellus). Non-native and stress tolerant species were also more abundant near one of the studied WWTPs when compared to the reference site, and the number of young-of-the-year fish collected did not vary along the effluent exposure gradients. Overall, we show that fish are attracted to wastewater outfalls raising the possibility that these sites may act as an ecological trap., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Dental development was reconstructed in several individuals representing four species of catarrhine primates--Symphalangus syndactylus, Hylobates lar, Semnopithecus entellus priam, and Papio hamadryas--using the techniques of dental histology. Bar charts assumed to represent species-typical dental development were constructed from these data and estimated ages at first and third molar emergence were plotted on them along with ages at weaning, menarche, and first reproduction from the literature. The estimated age at first molar emergence appears to occur at weaning in the siamang, lar gibbon, and langur, and just after weaning in the baboon. Age at menarche and first reproduction occur earlier relative to dental development in both cercopithecoids than in the hylobatids, suggesting that early reproduction may be a derived trait in cercopithecoids. The results are examined in the context of life history theory.

Gene transduction of hematopoietic progenitors capable of reconstituting both primary and secondary recipients is an important milestone in preclinical development of gene therapy. Myeloablation conditioning prior to infusion of transduced stem cells causes significant host morbidity. In contrast, drug-resistance gene transfer utilizes judicious in vivo selection of transduced stem cells over time, reaching only the level of transduction and expression required. The O(6)-benzylguanine (BG)-resistant mutant O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a potent selection gene for transduced cells. Using two different mutant MGMTs, G156A and P140K, that vary in BG resistance by a factor of 1:20, we asked whether long-term repopulating and secondary mouse-repopulating cells could be transduced, transplanted, and selected for in the nonmyeloablated recipient and whether the mutant MGMT would continue to be expressed in secondary recipient repopulating cells. We found that under stringent drug-selection competition, cells expressing the more BG-resistant variant, P140K-MGMT, were enriched over G156A-MGMT-expressing progenitors. In addition, the MFG retroviral vector transmitted the mutant MGMT gene to long-term repopulating cells that, after selective enrichment in the nonmyeloablated primary recipient, repopulated secondary mice and continued to express the transgene. Thus, MFG mutant MGMT vectors transduce repopulating hematopoietic stem cells that may be used both for chemotherapeutic drug resistance and to enrich for second therapeutic genes.

Gene therapy of cancer has been one of the most exciting and elusive areas of therapeutic research in the past decade. Critical developments have occurred in gene therapy targeting cancer cells, cancer vasculature, the immune system, and the bone marrow, itself often the target for severe toxicity from therapeutic agents. We review some recent developments in the field. In each instance, clear preclinical models validated the therapeutic approach and efforts have been made to evaluate the target impact in both preclinical and early clinical trials. Although no cures can consistently be expected from today's cancer gene therapy, the rapid progress may imply that such cures are a few short years away.

To define more precisely populations in which hemochromatosis is frequent to rare, problems of racial classification are introduced, with particular reference to Europeans and African-Americans. Because the category "Caucasian" includes a multitude of dissimilar peoples, the categories Europeans and European-Americans have been substituted for Caucasian, which is archaic. The background of discrimination in sickle hemoglobin programs for African-Americans are then analyzed, including, discrimination by employers, life insurance, and selective mandatory testing. Discrimination and selective testing of African-American employees of the Lawrence Livermore Laboratory continues today without prior consent, as it has since the 1970s. Dissimilarities between the genetics of hemochromatosis in Europeans and their descendants, Africans, and African-Americans are briefly analyzed. Finally, it is concluded that because hemochromatosis is unlike sickle hemoglobin in that it is potentially preventable and treatable, prevention and treatment principles should apply as in other diseases. Furthermore, because hemochromatosis is so common in European-Americans, discrimination, if practiced, would not be selective for African-Americans.

The crypts outside St Bride's Church, London, contain a documented collection of skeletal remains dating from the mid-18th century. Some of these remains became mixed during post-war restoration work on the church. The worst example of such mixing involves ten infants that were boxed all together with their corresponding coffin plates. All the infants were aged between 1 and 4 years at death. Recognized skeletal aging criteria proved unsuccessful in identifying the bodies. A more precise method of age estimation was utilized in order to separate these individuals. Age was determined using the incremental markers found in dental microstructure which are thought to be formed in circadian and circaseptan rhythms. The resulting age estimates were compared with the real ages obtained from the coffin plates and death certificates. Confident identification was achieved in eight out of ten cases. This study illustrates the potential value of a little-known aging method in circumstances where commonly used methods have proved unsuccessful.

Interspecific analyses of infant growth and the time to maternal reconception (or weaning) demonstrate a consistent threshold for weaning weight at close to four times neonate weight, irrespective of the duration of lactation (Lee et al., [1991] J. Zool. Lond. 225:99-114). Intraspecific variation in the attainment of a threshold weaning weight was determined in a sample of 31 captive infant rhesus macaques, where growth between birth and subsequent parturition was measured along with information on maternal size, weight, and social characteristics. A threshold weaning weight was found, with infants attaining approximately 1,335 g at the time of reconception. Birth weights of the infants were influenced by maternal physical and social variables in that larger mothers, and alpha ranking mothers, produced larger neonates. Postnatal growth rate, which determined the attainment of the threshold weight, was independent of maternal size or condition, but was influenced by offspring sex and the probability of reconception. Future reproductive status of mothers was specifically related to differences in patterns of growth among the infants. Mothers who conceived again at 30 weeks had infants who grew more slowly after the first 12 weeks of life, especially if these infants were sons. Mothers in this colony appeared to make decisions about the need to sustain their infants' growth in relation to their ability to invest in current offspring, which may compromise their subsequent reproduction.

A simpler, more economical technique than previously reported, that of conventional polyacrylamide gel electrophoresis alone, is described for the detection of asymmetric hemoglobin hybrids of the forms alphaXalphaYbeta2 and alpha2betaXbetaY when bloods from individuals with alpha and beta chain variants were examined. The presence of alpha chain variant hybrids, never before reported, is further evidence that hybrid formation is a more widespread phenomenon than has previously been thought of. Hybrids were found in artificial mixtures of hemoglobins and more importantly, are also reported here for the first time in bloods of individuals heterozygous for hemoglobin variants. These hybrid tetramers were as stable as the parent hemoglobins when examined under anaerobic conditions. The involvement of HbF in the formation of hybrids of the type alpha2betagamma is reported, and an analysis of the possible role of these as well as alpha2betaAbetaS hybrids in the sickling process is presented.

There is no specific therapy for sickle cell disease, and there is no evidence that sickle hemoglobin screening by conventional methods will lead to a significant reduction in the number of children with sickle cell disease. Thus it follows that if there is to be a national program to prevent sickle cell disease, the only recourse is one based on prenatal diagnosis and selective abortion of affected embryos or fetuses. Present-day dire poverty and callous health care public policies lead to the inescapable conclusion that a concerted attempt to alleviate poverty and its consequent adverse effects on maternal, neonatal, and infant mortality should take precedence over, or at the least coincide with, a national program to prevent sickle cell disease. On the other hand, it is argued that a woman should have the right to decide whether or not she wishes to have a child with a genetic disorder, and that recent advances in research on prenatal diagnosis, particularly when supported by public funds, should be made available to all, and not just the affluent.

Examination of blood samples from 1,183 individuals from Cameroon indicates that sickle cell trait frequencies and G6PD deficiency frequencies were heterogeneous among villages as well as within geographic areas and ethnic groups. Mean parasite counts were significantly correlated with Hb AS frequencies for children 6 years of age and under, although no correlation was found for mean parasite counts and G6PD deficiency frequencies. The mean age of sickle cell trait individuals was found to be significantly greater than the mean age of Hb AA individuals. The mean age of G6PD-deficient males did not differ from the mean age of G6PD-normal males. Hb AA and Hb AS children did not differ significantly in mean positive parasite counts. Falciparum malaria appears to be a selective pressure keeping Hb S frequencies high; yet it may not be the major selective force maintaining the G6PD polymorphism.

Hb Chicago is a newly discovered hemoglobin variant which was present in a Black newborn baby and her father. The leucine residue at alpha 136, which normally participates in the contact with the heme group, is replaced by a methionine residue. The two heterozygotes were clinically well with normal hematological data. Isolation of the alpha X and alpha A chains by reverse phase high performance liquid chromatography and hydrolysis of these chains with dilute formic acid at 110 degrees C for 24 hours, followed by separation of the resulting peptides by reverse phase high performance liquid chromatography, greatly facilitated the final identification of the abnormality. The baby and both parents had a -G gamma-G gamma-globin gene arrangement on one chromosome (normal: -G gamma-A gamma-) which explains the high G gamma values in the Hb F of these three persons.

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell trait was determined in 371 Cameroonian males and 668 male blood donors in Chicago. The number of males with both sickle cell trait and G6PD deficiency was significantly greater than expected (p less than 0.05) in Cameroon. The number of males with both sickle cell trait and G6PD deficiency in the Chicago population also exceeded the exptected number, although this was not statistically significant (p greater than 0.30). A young red cell population associated with the sickle cell gene leading to elevated G6PD levels in G6PD-deficient males suggests that sickle hemoglobin may exert a beneficial effect on G6PD deficiency, rather than the opposite, as had previously been proposed. These red cells may be better able to deal with oxidative stress, which can precipitate severe hemolytic disease in G6PD deficiency.

One-half of the twenty amino acids of the genetic code are just one mutational step away from the chain-terminator codons UAA, UAG, and UGA. It is postulated that somatic mutation to terminator is a hazard to which the organism has and to respond by adjusting certain proteins in the direction of fewer mutable residues. This view is supported by calculations based on the primary structure of five of the human hemoglobin chains. Each chain is scored for mutability to terminator in accord with the numbers and kinds of amino acids present. Among the adult chains, the most essential one, the alpha, has lowest mutability. The beta and delta follow, and in order of the presumed harm to the organism of a shortage of chain copies. Ante-natal chains tend to have higher mutabilities, supporting the view that cumulative mutational change in DNA can do little if the gene ceases to transcribe early in life. Two other predicitons based on the supposition of effective selection against mutability to terminator are also met: chain length of polypeptides is negatively correlated with their scores for mutability to terminator, and examination of the recently determined sequence of beta messenger RNA shows preferential use of codons that are not readily mutable to terminator.

The technique of heat denaturation was used in addition to electrophoresis for the detection of thermostability variants of hemoglobin and glucose-6-phosphate dehydrogenase in an attempt to measure the amount of genetic variability present in villages in the United Republic of Cameroon, Equatorial Africa. A minimum of three to a maximum of 13 thermostability variants were estimated for HbA and HbS, and a minimum of two to a maximum of ten thermostability variants were estimated for GdA, GdB, and GdA-. It is suggested that hemoglobin and glucose-6-phosphate dehydrogenase thermostability variants are genetically determined and that the sites of these variants are at the hemoglobin and glucose-6-phosphate dehydrogenase structural loci. The evidence for the existence of these hidden variants and their importance in the neutralist v. selectionist controversy are discussed.

A modification of the acid elution procedure for the demonstration of fetal hemoglobin in red cells using fast green stain is described. This technique not only permits improved visual estimation of the amount of fetal hemoglobin in red cells, but allows for the direct quantitation of fetal hemoglobin content of individual cells, using a scanning and integrating microdensitometer. As an application of this method, the distribution of fetal hemoglobin in populations of red cells of individuals was determined. Distributions were examined in sickle cell anemia patients with different proportions of fetal hemoglobin.