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At least 433 records · Page 24Linked to original sources
PubMed1997

The difficulty of identifying genes in anonymous vertebrate sequences.

The identification of genes in newly determined vertebrate genomic sequences can range from a trivial to an impossible task. In a statistical preamble, we show how "insignificant" are the individual features on which gene identification can be rigorously based: promoter signals, splice sites, open reading frames, etc. The practical identification of genes is thus ultimately a tributary of their resemblance to those already present in sequence databases, or incorporated into training sets. The inherent conservatism of the currently popular methods (database similarity search, GRAIL) will greatly limit our capacity for making unexpected biological discoveries from increasingly abundant genomic data. Beyond a very limited subset of trivial cases, the automated interpretation (i.e. without experimental validation) of genomic data, is still a myth. On the other hand, characterizing the 60,000 to 100,000 genes thought to be hidden in the human genome by the mean of individual experiments is not feasible. Thus, it appears that our only hope of turning genome data into genome information must rely on drastic progresses in the way we identify and analyse genes in silico.

Amino Acid Sequence↗
PubMed1976

Allelic restriction: a biologic alternative to multifactorial threshold inheritance.

Contrary to the argument regarding the conservatism of the multifactorial threshold model for describing the inheritance of congenital malformations, little biological insight has resulted from the series of tautological, albeit grandiose, mathematical assumptions currently comprising the basis for this hypothesis. The working hypothesis of this presentation is to apply the "allelic restriction" model to the genesis of common human congenital malformations. New population data concerning isolated cleft palate closely fit the predictions of the proposed hypothesis. Recognising the heterogeneity of cleft palate as well as other common congenital malformations (namely, the difference between phenocopies, definable syndromes, and true hereditary cases), the "allelic restriction" model accords with the apparent greatly "reduced penetrance" of the heriditary cases. This model is meant to apply only to those congenital malformations which have both a high population frequency and a relatively small number of families showing an atypical type of vertical transmission.

Adult↗
PubMed1990

An analysis of thirty cases of orbital lymphangioma. Pathophysiologic considerations and management recommendations.

Thirty cases of orbital lymphangioma were reviewed. Clinical, imaging, and microscopic findings were integrated to develop a pathophysiologic construct and management guidelines. The basic lesion might be considered an abortive vascular system which arborizes among normal structures. Intrinsic hemorrhage expands portions of the small-caliber network into large blood cysts, prompting clinical recognition. While major hemorrhage led to early surgery in 12 cases, long pretreatment intervals could be analyzed in 17 others. Twelve patients had second hemorrhages of varied magnitude, from 2 weeks to 15 years after initial recognition; five patients did not in an average of 6.8 years. Some blood cysts contracted spontaneously. Among 23 operated cases, 12 patients had major new bleeds from 4 days to 12 years after initial surgery; 11 patients did not in an average of 4.2 years. Poor final visual acuity was associated with multiple surgeries. The authors advocate conservatism in surgical case selection and in operative dissection.

Adolescent↗
PubMed2001

Risk assessment under FQPA: case study with chlorpyrifos.

Key science policies have had significant impact on the evolving implementation of the Food Quality and Protection Act (FQPA) (PL 104-170, 1996) by the US Environmental Protection Agency (EPA). The impact offour of these policies will be examined using the risk assessment for chlorpyrifos as a case study. These policies are selection of a regulatory endpoint, use of animal data without consideration of human data for setting the reference dose, a 10 FQPA safety factor and use of the 99.9 percentile of modeled consumer exposure in the acute dietary assessment. Each of these policy decisions had individual impact that was then compounded as cumulative impact on the revised risk assessment for chlorpyrifos conducted by the US EPA in 2000 [Federal Register Notice 65(159) (2000) 49982]. But embedded within each science policy, there are assumptions which may be too conservative and which together have resulted in a very large multiplicative reduction in the allowable exposure limits for chlorpyrifos in the US. These new exposure limits are quite different from other regulatory standards around the world. There is third party opposition to many of these policies and many believe the understanding of the relationship between exposure and what is known about human and animal responses to chlorpyrifos has been clouded. These changes in policy insert a new level of conservatism into the scientific statement of risk and create confusion that threatens to weaken the credibility of the regulatory process.

Animals↗
PubMed1999

Religious climate and geographical distribution of depressive symptoms in older Dutch citizens.

This study examines whether the degree of conservatism of the religious climate affects the geographical distribution of late life depressive symptoms. A U-shaped relationship is hypothesized: high levels of depressive symptoms at the extremes (both a-religious and hyperconservative), and a low level in the middle (moderate-conservative). Subjects are 3051 older Dutch citizens (55-85 years), living in 11 municipalities. Depressive symptoms are assessed using the CES-D. Religious climate is estimated on the municipality level, using percentages votes on political parties with a Christian background (moderate-conservative versus hyperconservative). Using multi-level analysis, the results support the U-curve hypothesis.

Aged↗
PubMed2000

Differential measures of 'sustained attention' in children with attention-deficit/hyperactivity or tic disorders: relations to monoamine metabolism.

Controversy exists on whether the constructs tested by paper/pencil and computerized continuous-performance tests (CPT) are similar, and the deficits recorded in children with attention-deficit/hyperactivity symptoms (ADHD) are comparable. Signal-detection measures were recorded on four such tests of 'sustained attention', with increasing working-memory requirements in healthy children (14; mean 10 years), and those with ADHD (14; mean 10 years) or a tic syndrome (TS, 11; mean 11 years). Clinical associations were sought from 24-h urinary measures of monoamine activity. The cancellation paper/pencil test revealed no group differences for errors or signal detection measures. On the CPT, ADHD children made more omission and commission errors than control subjects, but TS children made mostly omissions. This reflected the poor perceptual sensitivity (d-prime, d') for ADHD and conservative response criteria (beta) for TS children. This group difference extended to the CPTax, which was shown on a regression analysis to test for putative working-memory-related abilities as well as concentration. In all children, immediate response-feedback reduced omissions, and modestly improved d'. CPTax performance related negatively to dopamine metabolism in control subjects and to serotonin metabolism in the ADHD group. But comparisons between the metabolites in the ADHD group suggest that increased serotonin and decreased noradrenaline, with respect to dopamine metabolism, may detract from CPT performance in terms of d'. CPT tasks demonstrated a perceptual-based impairment in ADHD and response conservatism in TS patients independent of difficulty. Catecholamine activity was implicated in the promotion of perceptual processing in normal and ADHD children, but serotonin activity may contribute to poor CPTax (working-memory) performance in ADHD patients.

Adolescent↗
PubMedDate not supplied

Performance assessment model development and analysis of radionuclide transport in the unsaturated zone, Yucca Mountain, Nevada.

This paper describes the development and use of a particle-tracking model to perform radionuclide-transport simulations in the unsaturated zone at Yucca Mountain, Nevada. The goal of the effort was to produce a computational model that can be coupled to the project's calibrated 3D site-scale flow model so that the results of that effort could be incorporated directly into the Total System Performance Assessment (TSPA) analyses. The transport model simulates multiple species (typically 20 or more) with complex time-varying and spatially varying releases from the potential repository. Water-table rise, climate-change scenarios, and decay chains are additional features of the model. A cell-based particle-tracking method was employed that includes a dual-permeability formulation, advection, longitudinal dispersion, matrix diffusion, and colloid-facilitated transport. This paper examines the transport behavior of several key radionuclides through the unsaturated zone using the calibrated 3D unsaturated flow fields. Computational results illustrate the relative importance of fracture flow, matrix diffusion, and lateral diversion on the distribution of travel times from the simulated repository to the water table for various climatic conditions. Results also indicate rapid transport through fractures for a portion of the released mass. Further refinement of the model will address several issues, including conservatism in the transport model, the assignment of parameters in the flow and transport models, and the underlying assumptions used to support the conceptual models of flow and transport in the unsaturated zone at Yucca Mountain.

Calibration↗
PubMed2002

[The social and economic cost of diabetes mellitus].

OBJECTIVE: To evaluate the economic impact in terms of the direct costs (health care costs) and the indirect costs (effects on production caused by mortality and morbidity) of diabetes mellitus (DM) in the Canary Islands (Spain) during 1998. DESIGN: The approach used was to study the cost of the disease through looking only at people in the productive sphere (human capital). Direct and indirect costs were calculated by using costs of prevalence, i.e. the costs caused during 1998. SETTING: Direct costs were broken down into hospital care, primary care, out-patient consultations, drugs and further tests; indirect costs, into premature mortality and time off work. Measurements and main results. The total cost of DM amounted to 6468.76 million pesetas (38.88 millio ), or the equivalent of 126 168 pesetas (758.28 ) a year for each known diabetic patient. Total direct cost of DM was 4011.51 million pesetas (24.11 million ), which amounts to 2.13% of health expenditure in the Canaries; or the equivalent of 78 240 pesetas (470.23 ) a year for each known diabetic patient. Direct cost of health care was 62% of the total cost. Total indirect cost was 2457.25 million pesetas (14.77 million ), 38% of the total cost. CONCLUSIONS: Despite the conservatism of the approach, in that the study omitted costs linked to pain and suffering, permanent disability or home care by family members, the high social and economic cost of DM patients calls for cost-effectiveness studies that would permit a more transparent debate on this question.

Adolescent↗
PubMed1998

New equivalent sphere approximation for BFO dose estimation: solar particle events.

The use of a 5 cm tissue equivalent sphere model to obtain dose estimates for the blood-forming organs from energetic space radiations has been widespread for some time. Recent studies have noted that calculated doses obtained using the 5 cm equivalent sphere model were very conservatively overestimated when compared to those obtained with a detailed body geometry. Such conservatism may introduce significant shield weight penalties if used in spacecraft design studies. The use of detailed human geometry models will yield more accurate estimates of blood-forming organ doses and dose equivalents, but with a concomitant reduction in computational ease. In this work we propose a preliminary, yet new blood-forming organ equivalent sphere approximation for use in estimating SPE exposure and in shield design studies that is more realistic than the existing 5-cm approximation.

Aluminum↗
PubMed2003

The use of consumption data to assess exposure to biotechnology-derived foods and the feasibility of identifying effects on human health through post-market monitoring.

The pre-market safety assessment of foods derived through biotechnology provides a scientific basis for concluding reasonable certainty of no harm and ensuring safety. At a minimum, the outcome of such an assessment provides sufficient information to estimate the likelihood of adverse effects on consumers, generally precluding the need for post-market monitoring. Post-market monitoring (PMM) may be appropriate under certain conditions where a better estimate of dietary exposure and/or nutritional consequence of a biotechnology-derived food is required, when a potential safety issue, such as allergenicity, cannot be adequately addressed through pre-market studies, or to corroborate dietary intakes of a nutritionally improved food with beneficial effects on human health. Monitoring programs must be hypothesis-driven, and are dependent upon the availability of accurate consumption data. Exposure assessment methods include both deterministic and probabilistic estimates of intakes using food supply data, individual dietary surveys, household surveys, or total diet studies. In the development of a monitoring approach, resource allocation should be dependent upon both the desired level of conservatism and the endpoint of interest. However, the cost of monitoring varies substantially, and the potential to determine causation may be limited.

Diet↗
PubMed1980

Nevoid basal cell carcinoma syndrome: conservative dental treatment.

This report illustrates a conservative approach in the treatment of keratocysts involving the lower left canine in a case of nevoid basal cell carcinoma syndrome in a 10-year-old boy during 6 years' follow-up. The purpose of this report was to state the view of conservatism in the treatment of selected cases of keratocysts, based on close cooperation of the patient, orthodontist and oral surgeon. In this case, there are several keratocysts in both upper and lower jaws. Only the keratocysts associated with the lower left canine is considered to be conservatively treated in the presented case.

Basal Cell Nevus Syndrome↗
PubMed1998

Insulin-family peptide-receptor interaction at the early stage of vertebrate evolution.

This is an overview of our studies on insulin and insulin-like growth factor-I (IGF-I) interactions with their own and each other's receptors in the lamprey (Lampetra fluviatilis L.), an extant representative of the ancient vertebrate group of Agnathans as compared to mammal (rat). Lamprey insulin receptor shows species specificity, namely, it binds its own insulin with higher affinity than mammalian hormone. Nevertheless, and unlike mammalian insulin receptor, lamprey receptor discriminates relatively poorly between insulin and IGF-I. Autophosphorylation patterns are identical for both receptors. In contrast, IGF-I receptors in lamprey tissues are very similar to mammalian IGF-I receptors confirming known evolutionary conservatism of IGF receptor system. Presumed common evolutionary origin of insulin and IGF-I receptors and poor ability of lamprey insulin receptor to discriminate between two ligands, implies that lamprey insulin receptor is closer to putative ancestral protein that IGF-I receptor. Contrary to the common belief, ambient temperatures for lampreys (4-15 degrees C) put no constraints on either downregulation of receptors or the endocytosis of hormone-receptor complexes.

Animals↗
PubMed2001

Genomic organization of the gene for mouse PIASgamma and analysis of its promoter.

Signal transducer and transcriptional activator (STAT) proteins are latent cytoplasmic transcription factors that are activated in response to stimulation by various cytokines. Protein Inhibitors of Activated STAT (PIAS) proteins comprise a family of five mammalian proteins which have been identified as potentially important downregulators of the STAT signaling pathway. We have previously reported the identification and expression of the mouse homologue of PIAS family member PIASgamma. Here we report the isolation by genomic 5'-RACE PCR and in vitro analysis of the mouse PIASgamma promoter region and the genomic structure and organization of the mouse and human PIASgamma genes. Human PIASgamma spans approximately 23 kb on chromosome 19 and is organized into ten exons. The size of mouse PIASgamma is 16 kb and also organized into ten exons with the intron/exon structure of the two genes conserved in both species. As a result, considerable conservatism of the mouse and human intron sequences was observed. Analysis of a 1.4 kb genomic fragment containing the mouse PIASgamma promoter allowed us to map the transcription 'Start' site of the gene, determine the sequences essential for the activity of this promoter and to define a minimal promoter region.

Animals↗
PubMed2001

In vitro selection of enzymatically active lipase variants from phage libraries using a mechanism-based inhibitor.

The 'detergent lipase' Lipolase, from Thermomyces lanuginosa was subjected to a combinatorial protein engineering/phage display approach with the aim of identifying new enzyme variants with improved characteristics in the presence of detergents. First it was demonstrated that wild-type Lipolase could be produced in Escherichia coli retaining full activity and be displayed as an active enzyme fused to coat protein 3 on E. coli phage M13. A phagemid library designed to result in approximately two to three mutations per lipase gene was then constructed. Nine amino acids located in two regions close to the active site were targeted for randomization. Selections using a mechanism-based biotinylated inhibitor showed that phages displaying Lipolase could be specifically enriched from a population of control phages. Selections on a library phage stock in the presence of inhibitor and a commercial powder detergent resulted in a step-wise increase in the proportion of active clones. Analysis of 84 active clones revealed that they all expressed lipase activity, but with lower activities than that of a wild-type Lipolase-producing clone. In six of the seven most active clones a wild-type serine at position 83 had been replaced by threonine, a substitution known to alter the substrate chain length preference of Lipolase variants. Furthermore, the selection had enriched enzyme variants with a high degree of conservatism in one of the variegated regions, suggesting that this region is important for enzymatic activity and that the designed selection procedure was relevant. The selected variants contained primarily basic amino acid residues within the other variegated region. Taken together, the described results show that selection protocols based on enzymatic activity can be designed for this enzyme class which should be of importance for future protein engineering attempts.

Bacteriophages↗
PubMed1984

Current state of treatment of Dupuytren's disease.

On overview is present which briefly summarizes the incidence, pathology and natural progress of Dupuytren's Disease. The importance of recognizing the Dupuytren diathesis in planning the surgical treatment, the importance of conservatism in initiating surgery, and the principles of surgical management including dermofasciectomy are presented, and it is once again stressed that a distinction exists between recurrence and extension of Dupuytren's Disease post-operatively.

Dupuytren Contracture↗
PubMed1997

The young adult voice.

Young adulthood is notable for rapid physical changes and psychosocial instability. Care of the young adult professional voice requires knowledge of the specific anatomic and physiologic changes associated with the mutational voice, as well as the effects of general growth and maturation on the vocal mechanism. The effects of psychological stresses common to young adulthood, such as educational commitments and early career choices, must also be understood. Upper respiratory infection and allergies are common in this age group. Treatment of these conditions must be tailored in the professional voice user because of the potential side effects of some medications and the performance imperatives of the patient. Surgical indications for tonsillectomy in the young voice patient are discussed. There are no special considerations in the evaluation and treatment of laryngeal pathology in the young adult, with the exception of limiting the use of sedative anesthesia. However, conservatism in surgical decision-making is advised. The development of a stable, efficient vocal technique and a mature professional background requires time, patience, and hard work.

Adolescent↗
PubMed2005

Women in Arab countries: challenging the patriarchal system?

Progress in the empowerment of Arab women was found to be low in a 2002 report. Yet Arab women's status is not reflected in continuing high fertility, which in 2000 had dropped sharply in one generation to 3.4. This paper discusses why fertility decline could nevertheless have taken place in the Arab countries. Islam has not stood in the way of fertility decline, as Iran and Algeria show. From the mid- 1970s to 1980s, subsidised consumption through oil wealth redistribution reduced the cost of children, and social conservatism kept married women out of the labour force, both of which promoted higher fertility. The early stages of fertility decline were mainly due to longer length of education of girls, rising female age at first marriage, e.g. 28 in urban Morocco and 29 in Libya, and entry into the labour force of young, single women. There is also a growing population sub-group of never-married young women. Collapsing oil prices and structural adjustment reduced household resources and became an effective fertility regulation factor. Girls born since the 1950s have not only been educated longer than their mothers, but also their fathers, which increases their authority. These factors, and women's activism and civil and political lobbying for the reform of personal status now underway in a number of Arab countries, could all challenge the patriarchal system.

Adult↗
PubMed2005

Thinking beyond ICPD+10: where should our movement be going?

In this roundtable discussion, three long-time international activists in the field of reproductive and sexual rights discuss the challenges facing the feminist women's health movement ten years after the 1994 International Conference on Population and Development in Cairo, and the 1995 Fourth World Conference on Women in Beijing. Their conversation reflects on the nature of the global context in 1994-95 and how that context has changed a decode later, especially in light of growing conservatism and the growing HIV/AIDS epidemic. They consider the successes and limitations of the Cairo agenda and the strategic importance of taking a long-term view. In particular, they emphasise the need for strengthening health systems worldwide, advocating for better and more woman-friendly use of existing resources and building broader coalitions. Much of the conversation explores points of commonality and difference between feminist groups on the one hand, and medical and family planning organisations on the other, as well as ways of utilising such venues as the World Social Forum. Points of greatest promise internationally include the growing youth movement for sexual and reproductive health and rights and the potential for opening up larger alliances around sexual and bodily rights with HIV/AIDS activists, sex workers, people living with HIV and AIDS and human rights organisations.

Female↗