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Moderate dosage estrogen-androgen therapy improves continuation rates in postmenopausal women: impact of the WHI reports.

OBJECTIVE: The purpose of this report is not to provide descriptive data for practice recommendations but to point the way to more liberal thinking than the conservatism of today. The patients in this historical practice, where moderate dosages of estrogen are used, with androgens added when indicated, continue hormone replacement therapy (HRT) for many years. These women were audited to determine the reasons for continuance. DESIGN: During the 3 years from 1996 to 1999, 814 women have been followed prospectively, the date of this first visit recorded, as well as the date last seen, the years of hormone use, and their current hormone replacement, so that continuation rates could be determined. The records of the patients were reviewed in January 2005 to determine the impact of the Women's Health Initiative (WHI). RESULTS: Of the 814 patients, there were 573 surgically menopausal women with a mean age of 61.8+/-3.25 years and 241 naturally menopausal women with a mean age of 58.6+/-3.08 years. During the 3 years of observation, 692 women continued HRT while 122 discontinued their therapy. Of those continuing therapy, 606 were treated with the implantation of various combinations of estradiol and testosterone pellets, while 86 used injectables, patches or oral hormones. Continuation rates for pellet patients were 96.7% for 10 years, 88.8% for 20 years, and 21.9% for 40 or more years. Continuation rates for the other hormone users were 53.5% for 10 years and 20.9% for 20 years. Eighty-one percent of the patients were prescribed progestogens, and 18 different progestogens or dosages or regimens were used to individualize therapy and provide as side-effect-free a regimen as possible. Continuation rates in the 692 remaining patients declined to 66.7% during the next 5 years. CONCLUSIONS: Moderate dosages of estrogens, with androgens added when indicated, improve continuation rates. Therapy must be individualized so that not only are menopausal symptoms relieved but also side-effects are minimal and women continue to feel good. The implantation of estradiol and testosterone pellets is not necessary for even the majority of postmenopausal women. However, estrogen dosages must be adequate to provide a sense of well-being. After the WHI reports, continuation rates declined more rapidly.

Adult↗

Inheritance of antibody specificity V. Anti-2-phenyloxazolone in the mouse.

Antibodies to hapten 2-phenyloxazolone (phOx) of all BALB/c and DBA/2 mice have the same idiotype and the same major (public) isoelectric focusing pattern whose main spectrotype is called Ox-1. Neither of these characteristics could be readily demonstrated in anti-phOx antibodies of C57BL, C3H or LP mice; these antibodies were heterogeneous, and lacked public spectrotypes. Also, a fine specificty difference could be demonstrated between anti-phOx antibodies of BALB/c and C5MBL mice; the latter have a higher relative affinity than the former for a structural analogue of phOx (2-o-iodophenyloxazolone). The three BALB/c characteristics were inherited in congenic and recombinant inbred strains as an allotype-linked block, defining a new VH marker, VHphOx. Murine anti-phOx antibodies were found to exhibit three types of conservatism: (a) Every individual mouse of strains BALB/c, DBA/2 or BAB-14 had an almost indistinguishable IEF pattern. (b) These patterns (and the cross-reactive idiotype) remained virtually unchanged during an immunization course of 70 days. (c) An identical idiotype (and in some cases IEF pattern) was present in mouse strains of five different allogroups.

Animals↗

Lizards, lipids, and dietary links to animal function.

Our experiments were designed to test the hypotheses that dietary lipids can affect whole-animal physiological processes in a manner concordant with changes in the fluidity of cell membranes. We measured (1) the lipid composition of five tissues, (2) body temperatures selected in a thermal gradient (T(sel)), (3) the body temperature at which the righting reflex was lost (critical thermal minimal [CTMin]), and (4) resting metabolic rate (RMR) at three body temperatures in desert iguanas (Dipsosaurus dorsalis) fed diets enriched with either saturated or unsaturated fatty acids. The composition of lipids in tissues of the lizards generally reflected the lipids in their diets, but the particular classes and ratios of fatty acids varied among sampled organs, indicating the conservative nature of some tissues (e.g., brain) relative to others (e.g., depot fat). Lizards fed the diet enriched with saturated fatty acids selected warmer nighttime body temperatures than did lizards fed a diet enriched with unsaturated fatty acids. This difference is concordant with the hypothesis that the composition of dietary fats influences membrane fluidity and that ectotherms may compensate for such changes in fluidity by selecting different body temperatures. The CTMin of the two treatment groups was indistinguishable. This may reflect the conservatism of some tissues (e.g., brain) irrespective of diet treatment. The RMR of the saturated treatment group nearly doubled between 30 degrees and 40 degrees C. Here, some discrete membrane domains in the lizards fed the saturated diet may have been in a more-ordered phase at 30 degrees C and then transformed to a less-ordered phase at 40 degrees C. In contrast, the RMR of the unsaturated treatment group exhibited temperature independence in metabolic rate from 30 degrees to 40 degrees C. Perhaps the unsaturated diet resulted in membranes that developed a higher degree of disorder (i.e., a certain phase) at a lower temperature than were membranes of lizards fed the saturated diet. Our study demonstrates links between dietary fats and whole-animal physiology; however, the mechanistic basis of these links, and the general knowledge of lipid metabolism in squamate reptiles, remain poorly understood and warrant further study.

Adaptation, Physiological↗

A patient-centered paradigm: a model for chiropractic education and research.

Within the chiropractic profession there is concern over both the appropriate paradigm for educating the student and the appropriate research model for investigating health care and promotion. The purpose of this study was to identify, interpret, and describe a paradigm for chiropractic education and research. Chiropractic first principles and existing health care paradigms were identified and integrated with the characteristics of chiropractic practice described in sociological studies of the chiropractic profession. A patient-centered paradigm emerged, incorporating the principles of vitalism, holism, humanism, conservatism, naturalism, and rationalism. Characteristics of a patient-centered paradigm that were identified were then subjected to an eight-member consensus panel with representatives drawn from chiropractic education, research, and sociology. The characteristics of a patient-centered paradigm agreed upon include self-healing, recognition of the patient as a unified whole, respect for the patient's values, beliefs, and dignity, involvement of the patient as a partner in health promotion, and a natural and conservative approach to evidence based care. Patient-centered research must reach beyond the randomized controlled trial, involving designs where clinicians apply their own patient-centered therapy in a "real world" assessment. A pluralism of methods, including both qualitative and quantitative studies, needs to be designed and implemented. Patient-centered research is a process that is pragmatic, realistic, and grounded in the day-to-day experiences of both patients and chiropractors. A patient-centered paradigm offers a useful model to critically study what benefits patients and to prepare chiropractic students to practice in the patient's interest.

Chiropractic↗

Recognition of fossil prokaryotes in Cretaceous methane seep carbonates: relevance to astrobiology.

Recovery of prokaryotic body fossils from methane seep carbonates such as those of the Cretaceous Tepee Buttes of Colorado serves as a model for sampling in future astrobiological missions. The fossils, found primarily at the interface between paragenetic fabrics, suggest a sharp physicochemical gradient. Evidence of these microbial fossils occurs at a variety of scales. In the field, microbialite is found as meter-scale thrombolitic zones and centimeterscale stromatolitic crusts lining voids inferred to be the sites of ancient methane seepage. Petrographic fabrics suggestive of microbialite include indistinct peloids (0.1-1 mm in diameter) and crusts of authigenic micrite. Primary evidence obtained from scanning electron microscopy coupled with energy-dispersive x-ray spectroscopy analysis comprises pinnate bacteria (0.3 microm in diameter and 1-1.5 microm long), sheaths (2-4 microm in diameter), coccoids (0.5-1 microm in diameter, up to 40 per cluster), and the presence of framboidal pyrite (6-8 microm in diameter). These results are in agreement with studies of other ancient and modern seeps and suggest a morphological conservatism of microbial form that can be incorporated into studies of extraterrestrial environments where it is presumed that reduced gases drive the metabolic activity of prokaryote-like organisms. Target areas that could serve as conduits for reduced gas seeps include tectonic or impact-driven faulting, zones of cryosphere melting, or other disruptions in crustal coherence. Ancient seeps, preserved as localized anomalous evaporite deposits in the sedimentary cover, could be detected by remote sensing.

Carbonates↗

Thyroid hormone withdrawal in patients with differentiated thyroid carcinoma: a one hundred thirty-patient pilot survey on consequences of hypothyroidism and a pharmacoeconomic comparison to recombinant thyrotropin administration.

The study objective was to elucidate clinical, quality-of-life, and pharmacoeconomic effects of hypothyroidism secondary to thyroid hormone withdrawal (withdrawal) in athyroid patients with differentiated thyroid cancer (DTC). We also intended to compare societal costs of withdrawal and recombinant human thyroid-stimulating hormone administration (rhTSH) in this population. We mailed a 13-item pilot survey to patients with DTC who had undergone withdrawal before diagnostic whole-body scan (dxWBS). Using survey results and actual and estimated cost data, we retrospectively constructed a societal cost model comparing withdrawal versus rhTSH and performed a sensitivity analysis by increasing the conservatism of 8 assumptions about withdrawal costs. One hundred thirty (55%) of 236 patients answered the questionnaire. Among respondents, 92% had symptomatic and 85% multisymptomatic hypothyroidism. Almost half sought medical attention for hypothyroid complaints. Approximately one third drove motor vehicles while hypothyroid. Median absence from salaried work was 11 days per withdrawal. In the pharmacoeconomic model, societal costs per dxWBS were approximately 326 euro (25%) greater for withdrawal than for rhTSH. In the sensitivity analysis, societal costs of rhTSH exceeded those of withdrawal by approximately 307 euro (30%). In conclusion, hypothyroidism secondary to withdrawal causes important morbidity, safety risks, and productivity impairment. rhTSH avoids these drawbacks at roughly equivalent societal cost to that of withdrawal.

Adult↗

Food and nutrition: attitudes, beliefs, and knowledge in the United Kingdom.

In a study of 1700 members of the UK general public in 1992 in which face-to-face interviews were conducted, factors thought important in a healthy diet were (in descending order) more fiber, less sugar, less fat, less salt, and more starchy foods. Of common nutritional terms there was most confidence in explaining the meaning of fiber and least in the meaning of monounsaturated fatty acids. Most nutritional information came from the media but the credibility of this information was low. Fifty-three percent said that a conversation with their general practitioner (GP) was a source of advice they trusted. In a survey of 150 GPs and 50 practice nurses in 1992, lack of confidence was found to be common concerning the meaning of several nutritional terms, especially extrinsic sugars, NSP (nonstarch polysaccharide), and trans fatty acids. GPs were confident they could explain the link between diet and heart disease but were not sure about the value of starch in the diet. Both GPs and practice nurses were dissatisfied with their training in nutrition, both before and after registration. General practice staff thought that personal ill health was the most important motivator for dietary change among their patients. They thought that apathy and dietary conservatism were the most common barriers to people changing their diet. However, the public positioned lack of knowledge as the biggest obstacle. Surveys reported here showed that people's knowledge of sources of fat, calcium, and iron is often unreliable.

Adult↗

Phenotypic correlations among plant parts in Iberian Papilionoideae (Fabaceae).

BACKGROUND AND AIMS: Different plant organs may show varying degrees of form diversification or conservatism across phylogenetically related taxa. The present study uses data from a recent systematic study of Iberian Papilionoideae to investigate diversification and covariation in reproductive and vegetative plant parts. The appropriateness of imprecise (but comprehensive) taxonomic quantitative information is tested. METHODS: Organ size covariation and phenotypic correlations were studied among tribes, genera and species. Scale relationships were investigated by Reduced Major Axis regression. Variables used were the maximum dimensions of calyx, corolla, keel petal, fruit, seed, stipule, leaflet and petiole. KEY RESULTS: As regards tribe averages, the length of the corolla and that of calyx correlated positively and significantly. In contrast, pod length was unrelated to corolla size and largely tribe-specific. Within genera, the sizes of calyx, corolla and fruit sometimes covaried linearly (e.g. Lathyrus species) and other times did not (Genista, Astragalus). CONCLUSIONS: Information from taxonomic studies can be useful to establish major phenotypic correlations in plants. Results underscore the implications of tribal ownership in the Papilionoideae and illustrate the extensive morphological diversification of pods relative to flowers in this group.

Fabaceae↗

Enrichment or depletion of a GO category within a class of genes: which test?

MOTIVATION: A number of available program packages determine the significant enrichments and/or depletions of GO categories among a class of genes of interest. Whereas a correct formulation of the problem leads to a single exact null distribution, these GO tools use a large variety of statistical tests whose denominations often do not clarify the underlying P-value computations. SUMMARY: We review the different formulations of the problem and the tests they lead to: the binomial, chi2, equality of two probabilities, Fisher's exact and hypergeometric tests. We clarify the relationships existing between these tests, in particular the equivalence between the hypergeometric test and Fisher's exact test. We recall that the other tests are valid only for large samples, the test of equality of two probabilities and the chi2-test being equivalent. We discuss the appropriateness of one- and two-sided P-values, as well as some discreteness and conservatism issues. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Data Interpretation, Statistical↗

AIDS-related policies, legislation and programme implementation in India.

This paper traces the evolution of AIDS-related policy and legislation in India from an initial response characterized by conservatism and discrimination to the development of a coherent national programme which aims to prevent the transmission of HIV and to develop support structures for people with HIV and AIDS. Examining the strategies, achievements and problems of specific components of the National AIDS Control Programme (NACP), the paper finds that the very progressive approach of national-level policy makers has been countered by conservative forces at the state and local levels. Little progress has been made, moreover, in incorporating HIV/AIDS prevention efforts into broader development and empowerment strategies. The paper concludes by considering the wider social context of AIDS in India and the role of more far-reaching policy measures.

Acquired Immunodeficiency Syndrome↗

Psychiatry and race during World War II.

Although the American literature on "war neuroses" expanded during World War II, psychiatrists remained more interested in dramatic instances of "combat fatigue" than in the problems of soldiers who broke down far from the field of battle. This bias in the medical literature shaped both diagnosis and treatment. It had an especially powerful effect on African American soldiers who, in the "Jim Crow" army of World War II, were assigned in disproportionate numbers to service units. When military neuropsychiatrists did write about troubled young African Americans, many revealed a racial conservatism that was surprising given the liberal environmentalist paradigm of the day. (Here, a particularly useful source is the two-volume history of Neuropsychiatry in World War II, produced by the Medical Department of the U.S. Army.) The major challenge to such views came from the National Medical Association (NMA). Despite its many criticisms of military medicine, the NMA argued that African American soldiers and veterans needed more, not fewer, psychiatric services. NMA members also joined their white counterparts in the campaign to diminish the stigma of mental illness, especially among the families of soldiers returning home. We need more investigation of the subsequent history of race and psychiatry, especially within the Veterans Administration.

Black or African American↗

Estimated consumption and eating frequency of olestra from savory snacks using menu census data.

Potential chronic (14-d average) and acute (single-day) estimated daily intakes (EDI) were computed for olestra, a fat replacement intended for use in preparing savory snacks. The EDI were computed from eating occasions reported during a 14-d Menu Census survey among 4741 consumers; values were increased by 10% for conservatism. The eating occasions included all meals and in-between meal occasions eaten at home or away. Data from only those individuals who ate savory snacks at least once during the 14 d were used; this included 3820 individuals (81% of the sample) and represented a total of 16,067 eating days (24% frequency). The estimated mean chronic intake ranged from 1.8 to 4.7 g/d, depending on age and gender; at the 90th percentile, the range was 4.1-11.0 g/d. For all ages and both genders, the estimated mean intake was 3.1 g/d. Estimated acute intakes at the mean and 90th percentile ranged from 5.5 to 16.5 g/d and from 10.2 to 24.0 g/d, respectively, depending on age and gender. For all ages and both genders, the estimated mean intake was 10.2 g/d. The lack of parity in the chronic and acute intake estimates indicates that savory snacks are not eaten on a daily basis by the majority of snack eaters. The survey data were analyzed to understand the potential temporal eating patterns of olestra from savory snacks. When snacks were consumed, on average, 69% of the eating occasions were with main meals and 31% were between meals. Savory snacks did not contribute a major fraction of total food to the diet; only 7 and 18% of main meals contained a savory snack food at the 50th and 90th percentile, respectively. For the 50th-percentile consumer (all ages, both genders), savory snacks were eaten four times during the 14-d survey period, and the eating occasions occurred on 3 d. Comparable results for 90th-percentile consumers were 10 eating occasions and 8 eating days.

Adolescent↗

KpnI families of long, interspersed repetitive DNAs in human and other primate genomes.

KpnI restriction of DNAs from all anthropoid primates studied releases a conspicuous series of segments representing families of long, interspersed repetitive DNAs termed here the KpnI 1.2, 1.5, 1.8 and 1.9 kb families. Human KpnI 1.2 to 1.9 kb segments representative of these families were isolated and separately cloned in the KpnI site of a plasmid pBK5, specially constructed for this purpose. The KpnI clones did not cross-hybridize with cloned, primate alphoid sequences, suggesting that the KpnI families represent sequences separate and distinct from the alphoid DNAs. Secondary restriction analyses of cloned KpnI segments demonstrated microheterogeneity among individual members within the same KpnI family. Autoradiograms of capuchin monkey, AGM and human DNA cleaved with HaeIII, AluI or RsaI and hybridized to various cloned human KpnI sequences demonstrated a remarkable conservatism and relative simplicity in the organization of the KpnI families in the genomes of these widely divergent primates. The KpnI 1.2 kb and 1.5 kb families occur in high frequency (15%) among all plaques in two recombinant human genome libraries. Evidence is presented suggesting that the bulk of the KpnI families occur in the genome as clusters or congeries of higher molecular weight segments (greater than 2 kb) containing sequences homologous to the low molecular weight segments (1.2 to 1.9 kb).

Animals↗

A highly conserved nuclear gene for low-level phylogenetics: elongation factor-1 alpha recovers morphology-based tree for heliothine moths.

Molecular systematists need increased access to nuclear genes. Highly conserved, low copy number protein-encoding nuclear genes have attractive features for phylogenetic inference but have heretofore been applied mostly to very ancient divergences. By virtue of their synonymous substitutions, such genes should contain a wealth of information about lower-level taxonomic relationships as well, with the advantage that amino acid conservatism makes both alignment and primer definition straightforward. We tested this postulate for the elongation factor-1 alpha (EF-1 alpha) gene in the noctuid moth subfamily Heliothinae, which has probably diversified since the middle Tertiary. We sequenced 1,240 bp in 18 taxa representing heliothine groupings strongly supported by previous morphological and allozyme studies. The single most parsimonious gene tree and the neighbor-joining tree for all nucleotides show almost complete concordance with the morphological tree. Homoplasy and pairwise divergence levels are low, transition/transversion ratios are high, and phylogenetic information is spread evenly across gene regions. The EF-1 alpha gene and presumably other highly conserved genes hold much promise for phylogenetics of Tertiary age eukaryote groups.

Animals↗

Reliability of the ICRP's dose coefficients for members of the public, II. Uncertainties in the absorption of ingested radionuclides and the effect on dose estimates. International Comission on Radiological Protection.

Data on the gastrointestinal absorption of 12 elements have been reviewed. In each case, absorption is expressed as the fraction of the ingested element absorbed to blood, referred to as the f1 value, applying to intakes of unspecified chemical form by average population groups. The level of confidence in individual absorption values has been estimated in terms of lower and upper bounds, A and B, such that there is judged to be roughly a 90% probability that the true central value is no less than A and no greater than B. Ranges are proposed for intakes by adults, 10-year-old children and 3-month-old infants. Uncertainty in f1 values (B/A) ranged from 10% to factors of 100-400. The lowest uncertainties were for the well absorbed elements, H, I and Cs, for which there are good data, and the greatest uncertainties were for less well absorbed elements for which few data are available, particularly Zr and Sb. Ranges were generally wider for children and infants than for adults because of the need to allow for the likelihood of increased absorption with only limited data in support of the proposed values. The largest ranges were for 3-month-old infants, reflective lack of knowledge on the time-course and magnitude of possible increased absorption in the first few months of life. For each age group, ICRP values of absorption tend towards the upper bound of the ranges, indicating a degree of conservatism in th calculation of ingestion dose coefficients. Examination of the effect of the proposed confidence intervals for f1 values on uncertainties in dose coefficients for ingested radionuclides showed that there was no direct relationship. For some radionuclides, uncertainties in effective dose were small despite large uncertainties in f1 values while for others the uncertainties in effective doses approached the corresponding values for uncertainty in f1 values. These differences reflect the relative contributions to effective dose from cumulative activity in the contents of the alimentary tract, which in many cases is insensitive to uncertainties in f1, and cumulative activity of the absorbed radionuclide in systemic tissues, which is proportional to f1. In general, uncertainties in effective close for children and infants exceeded those in adults as a result of greater uncertainties in f1 values for the younger age groups. However, this effect was reduced in some cases by shorter retention times of absorbed nuclides in body tissues and organs.

Adult↗

Making progress in mental health policy in conservative times: one step at a time.

Progress in mental health services has been made incrementally in a sequence of policy steps. In recent years, in spite of political conservatism, progressive changes have advanced new principles of service delivery. Reports from the surgeon general and the President's New Freedom Commission on Mental Health advanced these principles, including recovery and evidence-based practices. Both of these high-level reports were influenced by the findings of the Schizophrenia Patient Outcomes Research Team (PORT). The Schizophrenia PORT established the effectiveness of mental health treatments and supports, which provided a scientific foundation for the optimistic focus on recovery and its expectation of improved outcomes for individuals with severe mental disorders. The PORT study also established the gap between treatment recommendations and actual services. Concern about this gap has motivated efforts to transform services by implementing evidence-based practices. Advances in broad mental health and social policy, coupled with continued advances in science, have the potential to improve the care of individuals who experience severe mental disorders, such as schizophrenia.

Evidence-Based Medicine↗

Evolution of variable and constant domains and joining segments of rearranging immunoglobulins.

The rearranging immunoglobulins (Igs) are a family of recognition and defense proteins found in all vertebrate classes. These proteins consist of two types of polypeptide chains; each of these contains a variable (V) domain, a joining (J) segment, and a constant (C) region, which can itself consist of one to four domains. The distinction between light and heavy chains is an ancient one phylogenetically that is reflected in the structures of V, J, and C regions. Despite the early emergence of these genetic elements, conservatism is apparent in the peptide structures encoded by V, J, and C exons. C regions of heavy chains did not evolve as single units; rather the individual domains show their own clustering patterns, which apparently are independent of heavy-chain designation or species. C-region domains of light chains and the T cell receptor beta chain are similar to one another and to the most carboxyl-terminal domain of heavy chains. Comparison of the light chains of sharks, bullfrogs, chickens, and mammals indicated that a phylogenetic distinction can be made between kappa and lambda light chains. V and J segments of the rearranging T cell receptors alpha, gamma, and delta are homologous to the corresponding segments of Igs, but their C regions form a group that is markedly distinct from those of conventional Igs and Tcr beta.

Amino Acid Sequence↗

Unilateral cleft lip-nose repair: a 33-year experience.

A 33-year experience with a proven method of repair for primary unilateral cleft lip-nose is presented. The technique used by the authors has been improved by modifications that have led to better symmetry and balance with less scarring. The technique involves ignoring the abnormal skeletal base, use of perisurgical passive orthopedics, and primary surgical correction of the nose and lip. Improved results can consistently be achieved by approaching the nose laterally through an inferior turbinate incision, freeing completely the lip and nose components so they can be translocated to match the normal side. Accurate positioning and symmetry of the alar base and sill is aided by limiting the transverse incision in the lip. This results in less scarring and improved sill reconstruction. The technique for floor-of-the-nose reconstruction avoids a small nostril without discarding any tissue. It is important to leave tissue in the floor to compensate for the skeletal deficiency. The senior author has performed this procedure in more than 750 patients. Approximately 35% have or will require minor secondary reconstruction at age 5 years. An aesthetic rhinoplasty is performed on most patients after growth is complete. Self-esteem is enhanced by early nasal reconstruction and has become the authors' standard of care for rehabilitation of the unilateral cleft lip and palate. Many surgeons remain reluctant to perform primary nasal repair. With careful proper technique, any experienced cleft surgeon can learn this procedure. For the beginner, conservatism is recommended.

Adolescent↗