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Homology-based gene structure prediction: simplified matching algorithm using a translated codon (tron) and improved accuracy by allowing for long gaps.

MOTIVATION: Locating protein-coding exons (CDSs) on a eukaryotic genomic DNA sequence is the initial and an essential step in predicting the functions of the genes embedded in that part of the genome. Accurate prediction of CDSs may be achieved by directly matching the DNA sequence with a known protein sequence or profile of a homologous family member(s). RESULTS: A new convention for encoding a DNA sequence into a series of 23 possible letters (translated codon or tron code) was devised to improve this type of analysis. Using this convention, a dynamic programming algorithm was developed to align a DNA sequence and a protein sequence or profile so that the spliced and translated sequence optimally matches the reference the same as the standard protein sequence alignment allowing for long gaps. The objective function also takes account of frameshift errors, coding potentials, and translational initiation, termination and splicing signals. This method was tested on Caenorhabditis elegans genes of known structures. The accuracy of prediction measured in terms of a correlation coefficient (CC) was about 95% at the nucleotide level for the 288 genes tested, and 97. 0% for the 170 genes whose product and closest homologue share more than 30% identical amino acids. We also propose a strategy to improve the accuracy of prediction for a set of paralogous genes by means of iterative gene prediction and reconstruction of the reference profile derived from the predicted sequences. AVAILABILITY: The source codes for the program 'aln' written in ANSI-C and the test data will be available via anonymous FTP at ftp.genome.ad.jp/pub/genomenet/saitama-cc. CONTACT: gotoh@cancer-c.pref.saitama.jp

Algorithms↗

The treatment of stimulant dependence.

Rehabilitation efforts offered to individuals with stimulant dependence incorporate a series of maneuvers to accomplish three major goals. Following active detoxification, most clinicians attempt to: (1) increase motivation for abstinence and maintain a high level of commitment to this goal; (2) help individuals to rebuild a stable life-style without substances; and (3) actively work toward ways of decreasing the probability of relapse (relapse prevention). While these activities incorporate education, counseling, outreach to families and exposure to self-help groups (e.g. Cocaine Anonymous), numerous pharmacological approaches have been tested. Each mode of drug therapy is based on a reasonable hypothesis, but appropriately controlled and structured clinical trials have not yet revealed any pharmacological approach for rehabilitation of stimulant-dependent individuals for which the risks have been shown to outweight the assets.

Amphetamines↗

Factors underlying anxiety in HIV testing: risk perceptions, stigma, and the patient-provider power dynamic.

Client anxiety is often associated with diagnostic testing. In this study, the authors used a grounded theory approach to examine the situational and social factors underlying anxiety associated with HIV testing, analyzing transcripts from semistructured interviews with 39 HIV test recipients in Ontario, Canada (selected based on HIV serostatus, risk experience, geographic region, gender, and number of HIV tests), then integrating emergent themes with existing research literature. Analysis revealed four themes: perceptions of risk and responsibility for health, stigma associated with HIV, the patient-provider power dynamic, and techniques used by test recipients to enhance control in their interactions with providers. Service implications include modifications to information provision during the test session, attention to privacy and anonymity, and sensitivity to patient-provider interactions.

AIDS Serodiagnosis↗

The underrecognition of HIV infection in women in an inner-city emergency room.

OBJECTIVES: This study analyzed the recognition of human immunodeficiency virus (HIV) infection and associated factors in women and men attending an emergency room in the Bronx, New York, NY. METHODS: From April 16, 1989, to May 5, 1989, the emergency room records of 2102 consecutive patients 13 years of age or older were reviewed and, for 856 patients undergoing venipuncture, linked anonymously to results of HIV antibody tested in excess blood. RESULTS: HIV seroprevalence was 7.8% in women and 14.6% in men. Among seropositive women, 5.0% had acquired immunodeficiency syndrome (AIDS), compared with 26.0% of men. Excluding patients with AIDS, HIV infection was recognized in 13.2% of women and 27.0% of men. HIV infection was recognized only in women aged 25 through 44 years. In men, recognition occurred in all age groups. Clinical presentation did not distinguish the seropositive from seronegative women. Risk assessments were recorded less frequently for women (11.2%) than men (15.9%). For 92.5% of persons with any behavioral risk assessment, injecting drug use was the only behavior assessed. CONCLUSIONS: HIV infection is underrecognized in women, in part, because of a lower prevalence of AIDS. Universal HIV risk assessment, which includes heterosexual behaviors, may help increase recognition of HIV in women and opportunities for early intervention.

Adolescent↗

An innovative method of collecting adverse events data.

Although adverse events are one gauge of hospital quality, determining the incidence and causes of adverse events is fraught with problems. This study tested a method to prospectively collect anonymous adverse events data using the Adverse Event Coupon. The results demonstrated the viability of the Adverse Event Coupon to collect adverse events data. Changes were made to the coupon based on feedback from registered nurses.

Adverse Drug Reaction Reporting Systems↗

Hepatitis B and hepatitis C seroprevalence and risk behaviour among community-recruited drug injectors in North West Wales.

We estimated the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and injecting risk behaviour, among community-recruited injecting drug users (IDUs) in North West Wales in 2001 and 2002. Sample collection was undertaken by trained current and former IDUs. Oral fluid samples (n = 153) were tested as part of the Unlinked Anonymous Prevalence Monitoring Programme ongoing survey of IDUs. Approximately 12% of the sample reported that they were currently in a drug treatment programme. Of the 153 samples screened 27% (95% CI 20%-34%, 41/153) were anti-HBc positive, and 23% (95% CI 16%-30%, 35/153) were anti-HCV positive. Sixteen per cent (95% CI 10%-22%, 25/ 153) of the samples were positive for both anti-HBc and anti-HCV. Of the subjects 15% (95% CI 9%-20%) knew they had been vaccinated against hepatitis B. Direct sharing of needles and syringes in the 28 days prior to interview was reported by 44% (95% CI 35%-54%), and sharing of any equipment including that used for drug preparation prior to injection was reported by 66% (95% CI 57%-76%). In North West Wales, syringe sharing is a common practice, and a high proportion of IDUs have been exposed to bloodborne viruses. Hepatitis B vaccination coverage within this population appears to be low and needs to be increased. Further efforts are needed to improve the availability of clean injecting equipment.

Adult↗

[Latex allergy in a hospital environment: results of a study in Sousse (Tunisia)].

Immediate allergy to natural latex has been on the icrease for the last decade in exposed persons and particularly the health personnel. Its prevalence is variable from one study to another. To evaluate the prevalence of later allergy in our nursing staff, we carried out an inguiry in two hospitals in Sousse. It's a prospective study involving 300 subjects and based on an anonymous questionnaire and a cutaneous prik test for latex allergy and atopy. The population was composed of 188 women an 112 men ith an average age of 35 years. There were 97 nurses of either sex, 65 doctors, 58 workers, 30 with technicians, 27 anesthetists, 17 midwives and 6 pharmacists. Sixty subjects (5.3%) showed a positive prick test ot latex: 11 women and 5 mon of different professional groups. The prevalence of atopy in this latex positive population (81%) was greater than in the latex negative population (25%). An associate alimentary allergy was identified in 10 patients allergic to latex. A study of specific immunoglobulins to latex carried out in 12 cases was positive in three patients. The provocation test for gloves was positive in 38% of cases.

Adult↗

[Prevention of HIV infection (AIDS)].

Principal elements of the HIV- and AIDS-prevention in the social field and health care are discussed. The infection with HIV as a sexually transmitted disease can only be prevented by personal caution in the sexual behavior. Counselling should in particular be addressed to risk groups such as homosexuals and drug abusers early enough and contribute to practising safer sex. General rules of behavior and of the hygienics in hospitals are described. The risk of infection by blood transfusion is relatively low, namely 1:300,000 to 1:3 Mio. The modalities of optional anonymous epidemiologic system of registration (report, testing, counselling, care) are discussed. Finally problems of the development of a HIV-vaccine are described, and the necessity to avoid discriminations of HIV infected or endangered persons is underlined.

AIDS Vaccines↗

The frequency of GJB2 and GJB6 mutations in the New York State newborn population: feasibility of genetic screening for hearing defects.

In the US, approximately one in every 1000 children has hearing loss sufficiently severe to interfere with the acquisition of normal speech [Ann NY Acad Sci 630 (1991) 16]. The causes of non-syndromic hearing loss (NSHL) are known to be heterogeneous, with genetic factors accounting for 50-75%[Am J Med Genet 46 (1993) 486]. Often individuals with NSHL thought to be caused by mutations in GJB2 have only one detectable mutant allele [Am J Hum Genet 62 (1998) 792, Hum Mol Genet 6 (12) (1997) 2173]. Another gene that has been identified as a possible cause of NSHL is GJB6 that codes for the gap junction protein, connexin 30. A consecutive series of anonymous newborn dried blood specimens (n = 2089) was tested for two GJB2 mutations: (i) 35delG, a pan-ethnic mutation; and (ii) 167delT, a mutation more frequently found in individuals of Ashkenazi Jewish and Mediterranean descents. Mutation detection was validated using allele-specific oligonucleotide hybridization in single wells. Once the positive samples had been identified, the samples were pooled and retested. All positives in the individual experiment were correctly identified in the pooled experiment. The same random set of anonymous newborn dried blood specimens plus some additional samples were tested (n = 2112) for the 342-kb deletion in the GJB6 gene.

Connexin 26↗

Mandatory anonymous HIV surveillance in Denmark: the first results of a new system.

OBJECTIVES: This paper describes the principles and first results of the newly implemented anonymous mandatory human immunodeficiency virus (HIV) reporting system in Denmark. METHODS: The system is based on a serially numbered form that is circulated among the laboratories, the physicians, and the national surveillance unit. All laboratories doing confirmatory tests for HIV antibodies must send a report form along with any positive test results. Before forwarding the form, the laboratory is to fill in the top part with the name and address of the requesting physician and send the back copy to the surveillance unit. The physicians are mandated by law to fill in the form with data on the patient and to keep two copies for their own files before sending the original to the surveillance unit. RESULTS: After a revision of the system, a response rate of 95% was obtained. CONCLUSIONS: We have established an anonymous mandatory HIV surveillance system in Denmark that enables routine evaluation of the completeness of reporting and nonresponding physicians to be reminded of their duty to report. Also, the physicians can act as mediators between patients and researchers; therefore, nested studies can be done without breaking the anonymity of the patient.

AIDS Serodiagnosis↗

Basic life support skills training in a first year medical curriculum: six years' experience with two cognitive-constructivist designs.

RATIONALE: Although the Basic Life Support (BLS) ability of a medical student is a crucial competence, poor BLS training programs have been documented worldwide. Better training designs are needed. This study aims to share detailed descriptions and the test results of two cognitive-constructivist training models for the BLS skills in the first year of medical curriculum. METHOD: A BLS skills training module was implemented in the first year curriculum in the course of 6 years (1997-2003). The content was derived from the European Resuscitation Council Guidelines. Initially, a competence-based model was used and was upgraded to a cognitive apprenticeship model in 2000. The main performance-content type that was expected at the end of the course was: competent application of BLS procedures on manikins and peers at an OSCE as well as 60% achievement in a test consisting of 25 MCQ items. A retrospective cohort survey design using exam results and a self-completed anonymous student ratings' questionnaire were used in order to test models. RESULTS: Training time for individual students varied from 21 to 29 hours. One thousand seven hundred and sixty students were trained. Fail rates were very low (1.0-2.2%). The students were highly satisfied with the module during the 6 years. CONCLUSION: In the first year of the medical curriculum, a competence-based or cognitive apprenticeship model using cognitive-constructivist designs of skills training with 9 hours theoretical and 12-20 hours long practical sessions took place in groups of 12-17 students; medical students reached a degree of competence to sufficiently perform BLS skills on the manikins and their peers. The cognitive-constructivist designs for skills training are associated with high student satisfaction. However, the lack of controls limits the extrapolation of this conclusion.

Clinical Competence↗

Translation of the short version of the Perinatal Grief Scale into Swedish.

INTRODUCTION: Women's emotions and grief after miscarriage are influenced not only by the context in which the miscarriage occurred but also by their past experience, the circumstances around the miscarriage and their future prospects. Their emotions therefore express a specific form of grief. Normally the time needed to work through the loss varies. A number of different scales, measuring women's emotions and grief after miscarriage have been published. One instrument that measures the specific grief, such as the grief after miscarriage is the Perinatal Grief Scale (PGS) that was designed to measure grief after perinatal loss and has good reliability and validity. AIMS: The purpose of this study was to translate the PGS into Swedish and to use the translation in a small pilot study. MATERIAL AND METHOD: The original short version of the PGS was first translated from English into Swedish and then back-translated into English, using different translators. During translation and back-translation, not only the linguistic and grammatical aspects were considered but also cultural differences. The Likert 5-point and a 10-point scale were tested in a pilot study where 12 volunteers anonymously answered the PGS twice. The intra-personal correlations were compared and analysed with weighted kappa-coefficient. FINDINGS: In all, five different versions were tested before the final Swedish version was established. The weighted kappa-coefficient for the volunteers was 0.58, which is regarded as representing good reproducibility. CONCLUSION: The PGS was translated successfully into Swedish and could be used in a Swedish population. As this work is rather time-consuming we therefore wish to publish the Swedish version so that it may be used by other researchers.

Abortion, Spontaneous↗

A unique community of family-oriented prostitutes in Nepal uninfected by HIV-1.

In the Mid Western and Far Western regions of Nepal live a unique group of prostitutes which maintains strong bonds resulting from 'untouchable' caste status and family tradition. Known as the Badis (pronounced 'bod ee'), it is estimated that well over 5000 Badi prostitutes are now actively engaged in the sex trade in Nepal. In 1991, a study of some of the social and cultural practices of this unique group was completed. In addition to the provision of counselling and information about STDs and AIDS, over 300 prostitutes were interviewed about their sex practices within the Badi community. Two hundred and twenty-eight Badi prostitutes consented to voluntary confidential testing for VDRL, and 250 consented to anonymous, unlinked serosurveillance for HIV-1. As previous studies have shown moderate to high rates of HIV-1 infection among prostitutes in general, and even higher rates of infection in low class prostitutes, some prevalence of VDRL as well as HIV-1 was expected. However, of the 228 Badi prostitutes tested, 154 (70%) were found to be VDRL positive, while none were found positive for HIV-1. At the same time, many of these prostitutes reported a history of constant and often untreated STDs. The implications for the future prevention of HIV infection in this group are obvious and striking. With immediate and effective STD treatment as well as counselling, the Badis represent one high risk group in which the global AIDS epidemic could be drastically reduced, or even averted.

Adolescent↗

Routine testing for HIV in the United States: the intersection between recommendations and practice.

The purpose of this study was to examine the current practices of family practice (FP) providers and their allied staff with regard to routine HIV testing in Rhode Island (RI) and Mississippi (MS). Anonymous experimenter-derived surveys were mailed to both groups of providers in 2002. The questionnaire contained five questions about their current practices and attitudes toward HIV testing as well as patient demographics. Five hundred twenty-one questionnaires were sent to American Academy of Family Practitioners (AAFP) members in RI and MS and to FPs with listings in the phone book in RI. The response rate was 52% in RI and 41% in MS. The vast majority of providers (93%) tested their high-risk patients for HIV, but less tested pregnant (57%) and other sexually active (37%) patients. The FPs in this survey wanted HIV testing to be done in the primary care setting, yet only 7% recommended HIV testing to their sexually active patients aged 18-50 in the previous year. In order not to stigmatize any specific risk group, nor to miss any patients who are unable to be identified as being "at high risk," routine testing in the primary care setting should be encouraged.

AIDS Serodiagnosis↗

Chinese geneticists' views of ethical issues in genetic testing and screening: evidence for eugenics in China.

To identify Chinese geneticists' views of ethical issues in genetic testing and screening, a national survey was conducted. Of 402 Chinese geneticists asked to participate, 255 (63%) returned by mail anonymous questionnaires. The majority of respondents thought that genetic testing should be offered in the workplace for alpha-antitrypsin deficiency (95%) and the predisposition of executives to heart disease, cancer, and diabetes (94%); that genetic testing should be included in preemployment physical examinations (86%); that governments should require premarital carrier tests (86%), newborn screening for sickle cell (77%), and Duchenne muscular dystrophy (71%); and that children should be tested for genes for late-onset disorders such as Huntington disease (85%), susceptibility to cancers (85%), familial hypercholesterolemia (84%), alcoholism (69%), and Alzheimer disease (61%). Most believed that partners should know each other's genetic status before marriage (92%), that carriers of the same defective gene should not mate with each other (91%), and that women should have a prenatal diagnosis if medically indicated (91%). The majority said that in China decisions about family planning were shared by the couple (82%). More than half had views that, in China, there were no laws to prohibit disability discrimination (64%), particularly to protect people with adult polycystic kidney disease (57%), cystic fibrosis (56%), or genetic predisposition to other diseases (50%). To some extent, these results might provide a basis for a discussion of eugenics in China, particularly about China's Maternal and Infant Health Care Law (1994).

Adult↗

Attitudes of Swiss mothers toward unrelated umbilical cord blood banking 6 months after donation.

BACKGROUND: During the past decade, the use of umbilical cord blood (CB) as a source of transplantable hematopoietic stem cells has been increasing. Little is known about the psychosocial consequences that later affect parents after unrelated CB donation. The objective of this study was to evaluate the attitudes of mothers toward unrelated donation of umbilical CB for transplantation 6 months after giving birth. STUDY DESIGN AND METHODS: A prospective study was performed with a standardized, anonymous questionnaire distributed to 131 women 6 months after CB donation. The questionnaire included topics concerning views about the ethical accuracy of having donated CB, emotional responses after donation, concerns about genetic testing and research with CB samples, attitude toward anonymity between her child and possible unrelated CB recipient, and willingness to repeatedly donate umbilical CB in a next pregnancy. RESULTS: The vast majority (96.1%) stated that they would donate umbilical CB again, and all respondents were certain that their decision to have donated umbilical CB was ethical. With regard to the potential risks of genetic testing and "experimentation" of umbilical CB, a significant correlation (p = 0.01) was found between negative attitudes and the decision not to donate umbilical CB again. Additionally, it was observed that women who had a negative experience concerning the donation of CB would not donate again (p = 0.004). CONCLUSIONS: This study shows a high degree of satisfaction of unrelated umbilical CB donation for banking in women 6 months after delivery. Despite a well-performed and detailed informed consent procedure, one of the ongoing issues for the donators in CB banking involves the concern regarding of improper use of the cells, such as genetic testing or experimentation. Accurate and detailed counseling of pregnant women and their partners therefore maximizes the likelihood that they will donate CB for unrelated banking. These data provide a basis for the improvement of donor selection procedures and public education regarding the use of CB for banking and transplantation.

Adult↗

HIV infection and zidovudine use in childbearing women.

OBJECTIVE: The risk of vertical HIV transmission from mother to child has been shown to be markedly decreased through HIV education, counseling, testing, and zidovudine (ZDV) use. The US Public Health Service published guidelines in 1994 for the use of ZDV on the basis of results of the AIDS Clinical Trials Group Protocol, a multicenter clinical trial of ZDV. The Public Health Service followed these guidelines with recommendations for routine HIV counseling and testing with informed consent for all pregnant women. New Jersey adopted these guidelines as the standard of care and created a program implementing the standard in all hospitals with maternity units. The purpose of this report was to study the trends in the rate of HIV infection in childbearing women over the past decade and to follow patterns of use of ZDV in the HIV-positive women, as a marker for the success of New Jersey's policy and program to reduce mother-to-child transmission. METHODS: Since 1988 in New Jersey, blood from heel-stick filter papers has been tested for the presence of HIV antibody through anonymous, unlinked surveys. Excess blood from screening for inborn errors of metabolism for all infants who were born in the state from July through September of each year was tested using a Food and Drug Administration-approved HIV-1 and Western blot test. Age, race, and ethnicity were recorded, as well as the results from the HIV-1 and Western blot tests. Since 1994, specimens confirmed to be HIV-1 positive by Western blot test were tested for the presence of ZDV, and the results were recorded. RESULTS: The number of New Jersey women included in the study for the period 1990 through 2002 numbered 372305. The percentage of childbearing women who tested positive for HIV declined by 55% during the period, although the declines were not uniform in all subgroups. In the early 1990s, women who were <30 years old had higher infection rates than older women, but this has not been a consistent pattern during the period. Younger women again had a higher rate in 2002. When HIV-positive rates are examined by 5-year age groups, the declines are dramatic for younger women. The rate per 100 women 20 through 24 years decreased from 0.46 per 100 tested women in 1990 to 0.29 in 2002 and for women 25 through 29 years from 0.51 per 100 in 1990 to 0.25 in 2002. The rate for women 30 through 34 years of age declined from 0.54 in 1990 to 0.13 in 2002. During the same time period, the rate per 100 tested women 35 though 39 years of age increased from 0.23 to 0.33. Black non-Hispanic women who give birth to live infants have the highest HIV-positive rates, followed by Hispanic women and white non-Hispanic women. In 2002, this rate was 0.74 per 100 in black non-Hispanic women, 0.22 per 100 in Hispanic women, and 0.08 in white non-Hispanic women. Although major disparities continue, the infection rate in black non-Hispanic women demonstrated the greatest decrease during the period, followed by the decline among Hispanic women. The use of ZDV in HIV-positive women increased dramatically during the period, from 13.3% in 1994, when it was first tested in New Jersey, to an all-time high of 88.5% in 2002. CONCLUSIONS: Reducing perinatal HIV transmission is a priority for the New Jersey Department of Health and Senior Services. Reducing perinatal transmission can be accomplished by reducing the number of infants who are exposed perinatally or decreasing the percentage of exposed infants for whom transmission occurs or both. The decrease in prevalence of HIV-positive status in childbearing women is in opposition to an overall increasing trend in prevalence rates. This decrease is thought to be attributable in part to the positive impact of numerous education and prevention programs but may also be the result of a voluntary decision on the part of HIV-infected women not to become pregnant or not to carry to term. In addition, the cohort of women who became infected in the early years of the epidemic may be aging out of their childbearing years, may have more advanced disease with a concomitant difficulty with fertility and carrying to term, or may have died. In New Jersey, a greater proportion of women with newly diagnosed HIV disease are past their childbearing years as compared with earlier years. Increased use of ZDV is thought to be attributable to several factors: dissemination of information to health care providers via continuing medical education activities; dissemination of information to the public, in particular to women; outreach via community-based organizations; and New Jersey Department of Health and Senior Service regulations and policies for mandatory counseling and voluntary testing of all pregnant women. A recent addition to New Jersey's comprehensive program to decrease perinatal transmission occurred in 2002 with dissemination to hospitals of the department's standard of care for women who present in labor with unknown HIV status. Physicians, nurses, and hospitals play vital roles in preventing vertical transmission of HIV by providing preconception and postconception counseling, testing with consent of pregnant women, and treatment for HIV-positive mothers, including administration of ZDV. This study not only provides an estimate of the prevalence of HIV infection in the population of childbearing women but also provides a means of examining the vertical transmission of HIV infection from mother to child. Continued research on this subpopulation as well as on other groups will provide additional knowledge to help in the overall goal of reducing HIV prevalence.

Adult↗