Contraceptive use and efficacy in a genetically counseled population.
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Adult↗
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Results for “Dynamic Programming”
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CaLMPhosKAN: prediction of general phosphorylation sites in proteins via fusion of codon aware embeddings with amino acid aware embeddings and wavelet-based Kolmogorov-Arnold network.
MOTIVATION: The mapping from codon to amino acid is surjective due to codon degeneracy, suggesting that codon space might harbor higher information content. Embeddings from the codon language model have recently demonstrated success in various protein downstream tasks. However, predictive models for residue-level tasks such as phosphorylation sites, arguably the most studied Post-Translational Modification (PTM), and PTM sites prediction in general, have predominantly relied on representations in amino acid space. RESULTS: We introduce a novel approach for predicting phosphorylation sites by utilizing codon-level information through embeddings from the codon adaptation language model (CaLM), trained on protein-coding DNA sequences. Protein sequences are first reverse-translated into reliable coding sequences by mapping UniProt sequences to their corresponding NCBI reference sequences and extracting the exact coding sequences from their GenBank format using a dynamic programming-based global pairwise alignment. The resulting coding sequences are encoded using the CaLM encoder to generate codon-aware embeddings, which are subsequently integrated with amino acid-aware embeddings obtained from a protein language model, through an early fusion strategy. Next, a window-level representation of the site of interest, retaining the full sequence context, is constructed from the fused embeddings. A ConvBiGRU network extracts feature maps that capture spatiotemporal correlations between proximal residues within the window. This is followed by a prediction head based on a Kolmogorov-Arnold network (KAN) using the derivative of gaussian wavelet transform to generate the inference for the site. The overall model, dubbed CaLMPhosKAN, performs better than the existing approaches across multiple datasets. AVAILABILITY AND IMPLEMENTATION: CaLMPhosKAN is publicly available at https://github.com/KCLabMTU/CaLMPhosKAN.
Codon↗
MaxSubSeq: an algorithm for segment-length optimization. The case study of the transmembrane spanning segments.
MOTIVATION: A problem in predicting the topography of transmembrane proteins is the optimal localization of the transmembrane segments along the protein sequences, provided that each residue is associated with a propensity of being or not being included in the transmembrane protein region. From previous work it is known that post-processing of propensity signals with suited algorithms can greatly improve the quality and the accuracy of the predictions. In this paper we describe a general dynamic programming-like algorithm (MaxSubSeq, Maximal SubSequence) specifically designed to optimize the number and length of segments with constrained length in a given protein sequence. Previous application of our algorithm, has proved its effectiveness in the optimization task of both neural network and hidden Markov models output, and in this paper we present the detailed description of MaxSubSeq. RESULTS: We describe the application of MaxSubSeq to the location of both helical and beta strand transmembrane segments, optimizing the outputs derived with different predictive algorithms. For all-alpha transmembrane proteins we use both the standard Kyte-Doolittle (KD) hydropathy scale and the TMHMM predictor (http://www.cbs.dtu.dk/). Using a set of 188 well characterized membrane proteins, MaxSubSeq nearly doubles the correct location of transmembrane segments as compared to the standard KD hydrophobicity plot, reaching 51% accuracy. If MaxSubSeq is used to optimize the TMHMM method the accuracy increases from 68 to 72%. When used to regularize the prediction of beta transmembrane strands, obtained using both a neural network and a HMM based predictors, MaxSubSeq increases the accuracy per protein up to 72 and 73% respectively. AVAILABILITY: The program is available upon request to the authors, or it is accessible through our web server (http://gpcr.biocomp.unibo.it/predictors/)
Algorithms↗
External control in Markovian genetic regulatory networks: the imperfect information case.
Probabilistic Boolean Networks, which form a subclass of Markovian Genetic Regulatory Networks, have been recently introduced as a rule-based paradigm for modeling gene regulatory networks. In an earlier paper, we introduced external control into Markovian Genetic Regulatory networks. More precisely, given a Markovian genetic regulatory network whose state transition probabilities depend on an external (control) variable, a Dynamic Programming-based procedure was developed by which one could choose the sequence of control actions that minimized a given performance index over a finite number of steps. The control algorithm of that paper, however, could be implemented only when one had perfect knowledge of the states of the Markov Chain. This paper presents a control strategy that can be implemented in the imperfect information case, and makes use of the available measurements which are assumed to be probabilistically related to the states of the underlying Markov Chain.
Algorithms↗
Using mRNAs lengths to accurately predict the alternatively spliced gene products in Caenorhabditis elegans.
MOTIVATION: Computational gene prediction methods are an important component of whole genome analyses. While ab initio gene finders have demonstrated major improvements in accuracy, the most reliable methods are evidence-based gene predictors. These algorithms can rely on several different sources of evidence including predictions from multiple ab initio gene finders, matches to known proteins, sequence conservation and partial cDNAs to predict the final product. Despite the success of these algorithms, prediction of complete gene structures, especially for alternatively spliced products, remains a difficult task. RESULTS: LOCUS (Length Optimized Characterization of Unknown Spliceforms) is a new evidence-based gene finding algorithm which integrates a length-constraint into a dynamic programming-based framework for prediction of gene products. On a Caenorhabditis elegans test set of alternatively spliced internal exons, its performance exceeds that of current ab initio gene finders and in most cases can accurately predict the correct form of all the alternative products. As the length information used by the algorithm can be obtained in a high-throughput fashion, we propose that integration of such information into a gene-prediction pipeline is feasible and doing so may improve our ability to fully characterize the complete set of mRNAs for a genome. AVAILABILITY: LOCUS is available from http://ural.wustl.edu/software.html
Algorithms↗
Operational factors affecting maternal mortality in Tanzania.
Identification of the main operational factors in cases of maternal death within and outside the health care system is necessary for safe motherhood programmes. In this study, a follow-up was done of all 117 cases of maternal deaths in Ilala district, Dar es Salaam, 1991-1993, at all levels of care. In all, 79% received some medical care whereas 11% arrived too late for treatment. For each case the major operational factors and all health care interventions were defined through interviews with family members and health care staff and from hospital records, and the avoidability of each case was determined. In the health institutions where the women had consulted, the available resources were assessed. It was found that in most cases the husband (29%) or the mother (31%) of the woman decided on her care in cases of complications, and together with the lack of transport, this often caused delay at home. Also, delay in transfer from the district hospital was common. Cases of abortion complications were often not managed on time because of the delay in reporting to hospital or misleading information. Suboptimal care was identified in 77% of the cases reaching health care. Inadequate treatment was identified by the district health staff in 61% and by the referral centres in 12% of their cases. Wrong decision at the district level and lack of equipment at the referral centre were the main reasons for inadequate care. It is concluded that although community education on danger signs in pregnancy and labour is important, provision of the core resources and supplies for emergency obstetric interventions, as well as clear protocols for management and referral, are absolutely necessary for improvement of maternal survival.
Developing Countries↗
Reducing perinatal mortality in developing countries.
The perinatal mortality rate (PNMR) is a key health status indicator. It is multifactorial in aetiology and is significantly influenced by the quality of health care. While there is an ethical imperative to act to improve quality of care when deficiencies are apparent, the lack of controls--when an interventions is applied to an entire service--makes it difficult to infer a causal relationship between the intervention and any subsequent change in PNMR. However, by specifically measuring avoidable perinatal deaths (those due to error or omission on the part of the health service), this limitation is partially overcome, and the impact of the intervention can be more rigorously evaluated. This paper reports the impact of perinatal audit in a rural African health district between 1991 and 1995. A total of 21,112 consecutive births were studied: the average number of deliveries increased by 31% from 325 to 424 per month. The PNMR (birth weight > or = 1000g) in 1991 was 27/1000, increased to 42/1000 in 1992, and fell steadily to 26/1000 in 1995 (40% reduction; p = 0.002). The proportion of avoidable deaths fell from 19% in 1991 to zero in the second half of 1995 (p = 0.0008). While factors associated with perinatal mortality are many, complex, and interrelated, this report suggests that mortality can be reduced significantly in resource-poor settings by improving quality of health care. Including the measurement of avoidable deaths in perinatal audit allows the impact of interventions to be more rigorously assessed than by simple measuring the PNMR.
Africa↗
Using perinatal audit to promote change: a review.
Close to half of all infant deaths world-wide now occur in the first week of life, almost all in developing countries, and the perinatal mortality rate (PNMR) is used as an indicator of the quality of health service delivery. Clinical audit aims to improve quality of care through the systematic assessment of practice against a defined standard, with a view to recommending and implementing measures to address specific deficiencies in care. Perinatal outcome audit evaluates crude or cause-specific PNMRs, reviewing secular trends over several years or comparing rates between similar institutions. However, the PNMR may not be a valid, reliable and sensitive indicator of quality of care at the institutional level in developing countries because of variations in the presenting case-mix, various confounding non-health service factors and the small number of deaths which occur. Process audit compares actual practice with standard (best) practice, based on the evidence of research or expert consensus. Databases reviewing the management of reproductive health problems in developing countries are currently being prepared so as to provide clinicians and health service managers with up-to-date information to support the provision of evidence-based care. Standard practice should be adapted and defined in explicit management guidelines, taking into account local resources and circumstances. Forms of process audit include the review of care procedures in cases which have resulted in a pre-defined adverse outcome, know as 'sentinel event audit'; and the review of all cases where a particular care activity was received or indicated, known as 'topic audit'. These are complementary and each depends on the quality of recorded data. The forum for comparing observed practice with the standard may be external, utilising an 'expert committee', or internal, in which care providers audit their own activities. Local internal audit is more likely to result in improvements in care if it is conducted in a structured and culturally sensitive way, and if all levels of staff are involved in reviewing activities and in formulating recommendations. However, further research is needed to identify the factors which determine the effectiveness and sustainability of perinatal audit in different developing country settings.
Developed Countries↗
Area variation in mortality from diseases amenable to medical intervention: the contribution of differences in morbidity.
Several conditions, whose timely and appropriate therapy should decrease case fatality, have been proposed as indicators of medical care quality for the National Health Service. Mortality rates for these diseases vary widely within the UK. To evaluate the contribution of varying incidence rates to these mortality differences, routinely collected morbidity and mortality data for 1974-1978 were analysed for 98 Area Health Authorities (AHAs) in England and Wales. Although differences in morbidity (as measured by hospital discharge and disease registration rates) and socioeconomic factors account for some of the area variation in mortality, significant heterogeneity persists after these factors are taken into account. This finding suggests that morbidity and socioeconomic factors are not the only determinants of mortality variation among areas for these particular diseases. Variation in quality of medical care may account for this result, although regional diagnostic and reporting differences and variation in disease severity among areas must also be considered.
Analysis of Variance↗
Black/white comparisons of deaths preventable by medical intervention: United States and the District of Columbia 1980-1986.
Blacks in the US experience increased mortality (1113 versus 745 per 100,000 males; 631 versus 411 per 100,000 females) and decreased life expectancy (63.7 years versus 70.7 years for males; 72.3 years versus 78.1 years for females); compared to Whites. In an effort to determine if the excess mortality among Black Americans might be explained by differences in access or quality of health care services, we performed a race-specific analysis of conditions for which mortality is largely avoidable given timely and appropriate medical care. Using methodology proposed by Rutstein and Charlton, mortality due to 12 causes was evaluated including tuberculosis, cervical cancer, Hodgkin's disease, rheumatic heart disease, hypertensive heart disease, acute respiratory disease, pneumonia and bronchitis, influenza, asthma, appendicitis, hernias and cholecystitis. In the US, during 1980 to 1986, an average of 17,366 deaths and 286,813 years of potential life (YPLL) before age 65 were lost each year due to all 12 sentinel causes combined. Of these causes, hypertensive heart disease, pneumonia and bronchitis, cervical cancer and asthma accounted for the greatest number of deaths. The mortality rate for all 12 causes combined among Blacks was 4.5 times that of Whites. The highest relative rates among Blacks compared to Whites were observed for tuberculosis, hypertensive heart disease and asthma. The overall mortality rate in the District of Columbia for the selected causes was 3.7 times the national rate. Compared to national rates, statistically significant elevated rates in the District were observed for tuberculosis, hypertensive heart disease and pneumonia and bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Time trends in cause-specific mortality in Estonia from 1965 to 1989.
BACKGROUND: During the last 30 years, in most developed countries, life expectancy has increased considerably. In Estonia, over the past half century, health and social policy was dictated by the Soviet socioeconomic system. In order to evaluate the consequences to health and to evaluate trends in health, cause-specific mortality was studied in Estonia. METHODS: The study was based on national death records from 1965 to 1989. Mortality rates were computed for all causes of death combined and for 16 cause groups. Age-standardization (European population) was performed using 5-year age groups. RESULTS: From 1965-1969 to 1985-1989, the age-standardized mortality rate for all causes combined increased by 4.0% for males and decreased by 1.5% for females. The greatest increase was observed for ages 45-54 among males (26.3%) and for ages 55-64 among females (7.0%). Very high death rates from circulatory diseases and high mortality from injuries and poisoning are of specific concern, particularly for males. Mortality from circulatory diseases continues to rise for ages 45-74 among males and for ages 55-64 among females. Mortality rates for neoplasms and endocrine disorders are also increasing; however, the mortality rates from respiratory and infectious diseases have shown a substantial decrease. CONCLUSIONS: Chronic diseases, together with injuries and poisoning, remain a serious public health problem in Estonia. Preventive measures, including earlier detection of diseases as well as changes in social security and individual health behaviour are needed to improve the health of the population.
Adolescent↗
Cancer mortality in Russia and Ukraine: validity, competing risks and cohort effects.
BACKGROUND: The dramatic increase in mortality in Russia and Ukraine in the late 1980s and 1990s has been due to increases in certain causes of death, particularly cardiovascular disease and accidents and violence. In contrast, there has been a slight fall in mortality from cancer. METHODS: This paper presents an analysis of trends and patterns in cancer mortality and examines four possible explanations for its recent fall: changes in data collection; cohort effects; competing mortality from other causes of death; and improvements in health care. RESULTS: All contribute to some extent to the observed changes, with each affecting predominantly different age groups. There is evidence of a significant underrecording of cancer deaths among the elderly especially in rural areas and of significant changes in coding practices in the early 1990s. Competing mortality from cardiovascular diseases and accidents can explain some reduction in male deaths from cancer in middle age. Birth cohort effects can explain some reduction among males after early middle age and among females at all ages. The impact of changes in health care are more difficult to identify with certainty but there is evidence of reduced deaths from childhood leukaemia. IMPLICATIONS: Recent changes in mortality in Russia are complex and their understanding will require a multidisciplinary approach embracing demography, epidemiology and health services research.
Adolescent↗
Asylum applications in the European Union: patterns and trends and the effects of policy measures.
"Statistics on asylum applications have been used in a highly selective way in the debates on refugees and asylum policies in Western Europe, to justify restrictive measures. This paper provides a more systematic analysis of these statistics. It focuses on the pattern of origins and destinations for asylum seekers in the European Union in the period 1985-1994.... When the patterns of origin and destinations are compared for separate years, it becomes clear that the destinations of asylum movements have been constantly changing. Though some of the more remarkable shifts were clearly related to policy measures in the relevant countries, many measures produced only limited effects or failed to have any effect at all."
Demography↗
Demographic correlates of low birth weight.
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Adolescent↗
Female age, the length of involuntary infertility prior to investigation and fertility outcome.
The objectives of this study were two-fold: firstly to determine whether female age exerts an influence on the fertility outcome of couples attending an infertility clinic, independent of demographic and clinical details; and secondly to examine the relationship between the length of involuntary infertility prior to investigation and the subsequent chance of conception. Seven-hundred-and-thirty-one subjects whose partner did not have azoospermia were recruited to the study. Female age ranged from 20 to 46 (mean = 31.1). The range of involuntary infertility prior to investigation was 12-216 (mean = 62) months. One-hundred-and-twenty-four women conceived. The following variables achieved the 5% level of significance when a stepwise analysis was performed on all cases; the concentration of spermatozoa exhibiting slow or sluggish linear or non-linear motility (chi 2(1) = 17.57, P less than 0.0001, RR = 1.67 per 50 x 10(6)), female age (chi 2(1) = 12.44, P = 0.0004, RR = 0.92 per annum), tubal status (chi 2(1) = 12.22, P = 0.0005, RR = 2.15), length of infertility before investigation (chi 2(1) = 11.22, P = 0.0008, RR = 0.87 per annum) and past paternity (chi 2(1) = 8.43, P = 0.0037, RR = 1.81). Female age was found to be positively correlated with the incidence and severity of ovulatory dysfunction, tubal occlusive disease, pelvic adhesions and endometriosis. Where the female partner was 'normal' on investigation, all conceptions were independent of treatment to either partner.(ABSTRACT TRUNCATED AT 250 WORDS)
Actuarial Analysis↗
Polypeptide folding of Bacillus cereus ATCC7064 oligo-1,6-glucosidase revealed by 3.0 A resolution X-ray analysis.
The crystal structure of an oligo-1,6-glucosidase from Bacillus cereus ATCC7064 was determined by the X-ray diffraction method at 3.0 A resolution. The structure was solved by the multiple isomorphous replacement method and refined to a crystallographic R-factor of 0.208, using the molecular dynamics refinement program, X-PLOR. The electron density map revealed the folding of a polypeptide chain consisting of 558 amino acid residues. The molecule can be subdivided into three domains (N-terminal domain, subdomain, and C-terminal domain). The N-terminal domain has an (alpha/beta)8-barrel structure called the TIM-barrel structure. The C-terminal domain is characterized by a beta-barrel structure composed of eight antiparallel beta-strands, while the subdomain has a loop-rich structure with a small alpha-helix and a beta-sheet. The enzyme has a large cleft between the N-terminal domain and the subdomain. The cleft leads from the molecular surface to the molecular center. The bottom of the cleft is at the C-terminal end of the parallel beta-strands of the (alpha/beta)8-barrel. These structural features closely resemble those of alpha-amylases from Aspergillus oryzae and pig pancreas.
Bacillus cereus↗
The changing face of community and institutional care for the elderly.
BACKGROUND: The NHS and Community Care Act 1990, implemented from 1 April 1993, was expected to alter profoundly the provision of domiciliary services to old people. This change needs to be compared with what would have happened if no action had taken place. We sought to identify trends in community and residential care before and after 1993 to facilitate this comparison. METHODS: Statistics were collated from diverse government publications and other authoritative sources. RESULTS: Between 1985 and 1993 there was a progressive contraction of public community and residential services, as well as hospital beds available to the elderly. The concomitant huge increase in places publicly funded in private old people's and nursing homes appears to have been little affected by the implementation of the NHS and Community Care Act. CONCLUSIONS: The NHS and Community Care Act has had little effect in curbing the institutionalization of old people, which has reached now the highest percentage this century at 7 per cent. A considerable expansion of community services would be required to return to the per capita provision of the early 1980s.
Aged↗
Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling.
A multiple sequence alignment algorithm is described that uses a dynamic programming-based pattern construction method to align a set of homologous sequences based on their common pattern of conserved sequence elements. This pattern-induced multi-sequence alignment (PIMA) algorithm can employ secondary-structure dependent gap penalties for use in comparative modelling of new sequences when the three-dimensional structure of one or more members of the same family is known. We show that the use of secondary structure information can significantly improve the accuracy of aligning structure boundaries in a set of homologous sequences even when the structure of only one member of the family is known.
Algorithms↗