bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review and Update on Adult Syphilis, with Particular Reference to its Treatment
Authors: Goldmeier D , Hay P
Published: January 2017

Syphilis has become less common in Europe in the last decade, but has once again become a major problem in the USA, and remains so in many developing countries. Several treponemal genes have now been cloned and expressed in Escherichia coli, allowing study of treponemal proteins. The importance of cell mediated immunity in syphilis has been demonstrated in animal models.

A diagnosis of syphilis is usually confirmed by dark-field microscopy or serological tests. Seroconversion may be delayed in HIV infected individuals. A positive reaginic test in cerebrospinal fluid (CSF) has a high specificity but low sensitivity in the diagnosis of neurosyphilis. Indeed, virulent treponemes can be identified in CSF samples which have negative reaginic tests, normal cell counts and protein levels. In the CSF, the FTA-Abs test has a high sensitivity but low specificity for neurosyphilis.

Penicillin remains the treatment of choice for all stages of syphilis, although it penetrates the blood brain barrier poorly. Treatment with intramuscular benzathine penicillin 2.4 million units stat, or 600,000 units procaine penicillin daily does not produce treponemicidal levels within the CSF. However, the incidence of neurosyphilis is low in immunocompetent patients treated with such regimens during early syphilis. Acceptable alternatives in penicillin-allergic patients include ceftriaxone and doxycycline. Erythromycin is not recommended as it has produced unacceptably high rates of treatment failure. Recently, a strain of macrolide-resistant Treponema pallidum was isolated from a patient with secondary syphilis. For the treatment of neurosyphilis, treponemicidal levels of penicillin can be achieved in the CSF using 2.4 million units procaine penicillin daily with concurrent probenecid 500 mg 4 times a day, or an intravenous infusion of benzyl penicillin 12–24 million units daily. Early syphilis can be treated adequately over 10 days, but 21 to 28 days is appropriate for late syphilis.

In HIV-infected patients syphilis may present atypically with initially negative serological tests. Treatment of early syphilis in HIV-positive patients has been associated with the early development of neurosyphilis. It is advisable to treat all patients co-infected with HIV with an antibiotic regimen that achieves adequate levels within the CSF.
Who Won't Tell: Predictors of Refusal to Report Number of Sex Partners
Authors: Peruga A , Kofie V Y , Martinez R M
Published: January 2017

Data from 1475 respondents to a telephone survey are used to examine whether those who refused to report the number of their sex partners in the 12-month period prior to the interview are more likely to engage in HIV risk behaviours than those who did report this number. Logistic regression shows that refusal is associated with being single of low education (ORadj = 8.0, 95% CI 2.7–23.7), using condoms in the last year (ORadj = 4.2, 95% CI 1.6–11.1), self-reporting of HIV-risk behaviours (ORadj = 3.6, 95% CI 1.3–9.6), and being male (ORadj = 2.7, 95% CI 1.1–6.6). These associations apply only to a subsample of individuals who provided complete information for HIV risk and other related behaviours. Results from the total sample indicate that individuals in our study who did not report their number of partners are more likely to have characteristics that are compatible with a higher probability of HIV risk practices. This pattern of associations suggests that refusers are indeed at higher risk for HIV infection than those sexually active individuals who did report the number of partners.
Sexual Behaviour and Use of the Condom by Men Attending Gay Bars and Clubs in Glasgow and Edinburgh
Authors: Gruer L D , Ssembatya-Lule G
Published: January 2017

How widespread are the safer forms of sexual behaviour reportedly adopted by male homosexuals in recent years? A questionnaire was completed by 173 and 83 gay men attending gay bars and clubs in Edinburgh and Glasgow respectively. Comparisons were made between those who reported using the condom ( n = 137, [54%]) and those who did not ( n = 119, [46%]). Sixty percent of respondents reported more than 5 partners during the previous year. Condom use was much less common among men with less than 5 years' experience as a practising homosexual. Less than one-fifth of respondents reported always using a condom during anal intercourse. Orogenital contact without a condom was reported by 84% of all respondents, and unprotected anal intercourse by 40%, (over 30% for those who used condoms). About one-third of condom users but only 14% of non-users thought they were at risk of catching HIV because of their sexual behaviour, although 80% of users and 70% of non-users said their lifestyles had been affected by the HIV epidemic. While there were some encouraging signs of behaviour change, unprotected anal sex is still widely practised. Gay bars and clubs represent important venues for conveying the safer sex message.
Factors Associated with Hepatitis B Infection
Authors: Hart G.
Published: January 2017

Men and women patients not previously immunized or tested, attending the Adelaide (South Australia) STD clinic from 1988–1991, were tested for hepatitis B infection, and potential risk factors detected by multiple logistic regression. Of 7055 men and 3425 women patients tested 811 (11.5%) men and 250 (7.3%) women were seropositive. Among men seropositivity was associated with being Asian (odds ratio (OR) = 14.5), being Aboriginal (OR = 2.2), homosexual behaviour (OR = 3.8), intravenous drug use (OR = 3.2) being over 24 (OR = 2.7), previous STD (OR = 1.8), being unemployed (OR = 1.3) and having sex outside the state in the past 3 months (OR = 1.3). Among women seropositivity was associated with being Asian (OR = 10.3), being Aboriginal (OR = 2.4), intravenous drug use (OR = 3.8), being over 24 (OR = 1.6) and having vaginal discharge or dysuria (OR = 1.4). Seropositivity was not independently associated with being a prostitute or having multiple sex partners in the past 3 months. Among seropositive individuals, risk factors were not readily identifiable for 15% of men and 43% of women. Univariate analysis may provide misleading indicators of risk factors because of the confounding influence of other factors, particularly intravenous drug use. In selective vaccination campaigns the target group should be determined on the basis of local circumstances. In South Australia this group should include men with an STD. The success of selective campaigns will be jeopardized by the failure to identify risk factors in many of those who become infected, and in such situations universal vaccination or widespread screening may be more appropriate strategies.
Anonymized Sero-Survey of HIV in a Genitourinary Medicine Clinic Population
Authors: Drake S M , Skidmore S J , Ratcliffe D , Radcliffe K , Shahmanesh M , White D
Published: January 2017

An anonymized sero-survey of the prevalence of HIV antibody was performed at an inner city Genitourinary medicine clinic in Birmingham. In 1991 8686 patients undergoing routine serological syphilis tests were anonymously tested for HIV antibodies once during the year. Demographic information was recorded for each sample but they were otherwise unlinked. There were 31 samples which tested positive for anti-HIV 1 from this group compared with 13 diagnosed by concomitant voluntary named testing. Sero-prevalence rates of 0.17% for women and heterosexual men and 4.37% for homosexual/bisexual men were found. No drug users tested positive. The survey provided evidence of occult disease outside the recognized risk behaviour patterns of homosexual men and injecting drug users outside London.
The Use of Pelvic Ultrasound in Female Patients Attending a GUM Clinic
Authors: Huengsberg M , MacDonald L M , Bradbeer C S
Published: January 2017

This is a retrospective review of 279 pelvic ultrasound examinations requested over 19 months by a department of GU medicine. An abnormal ultrasound was rarely seen in women with pain but no pelvic mass (16%). If a mass was found on bimanual palpation, the yield of abnormal ultrasound was much higher (52%). Pelvic ultrasound was also useful in refuting a diagnosis of ectopic pregnancy by demonstrating an intrauterine gestational sac.
Knowledge of HIV Transmission and Risk Behaviour in Kenyan Health Care Workers
Authors: Rogstad Karen E , Tesfaledet G , Abdullah Mohammed S , Ahmed-Jushuf Imtyaz H
Published: January 2017

In order to determine knowledge of HIV transmission, sexual risk behaviour and perception of risk in African health care workers, 200 employees at the Aga Khan Hospital, Nairobi, Kenya, were asked to complete an anonymous self-administered questionnaire. There was a 75% response rate. Twenty-five per cent believed that condoms were not protective against HIV transmission. Eighty-nine per cent believed oral sex to be a risk factor, as did 70% for kissing, 41% for masturbation of a partner and 43% for nursing an AIDS patient. Younger people were more likely to think condoms were ineffective ( P = 0.007) and that insect bites were a significant risk factor ( P = 0.004). Twenty-seven per cent had changed their sexual behaviour as a result of the AIDS epidemic, but 48% did not use condoms with non-regular partners. Four had current or previous homosexual relationships. Seventy per cent believed they were at risk of being HIV positive but only 12% had been tested. We have shown that even in the educated group, misconceptions regarding HIV transmission were high and many continue to be at risk for their sexual behaviour.

In addition, in-service training regarding HIV transmission should be considered for health care workers in Africa.
The Epidemiology of Genital Chlamydial Infection in South Australia
Authors: Hart Gavin
Published: January 2017

All laboratory tests performed and medical reports received in South Australia in 1990–1991 and screening results for Chlamydia trachomatis at the central STD clinic from 1988–1991 were analysed to clarify the epidemiology of genital chlamydial infection. From 70494 laboratory tests in 1990–1991, 2449 (3.5%) infections were detected of which 2431 (99%) were also reported by clinicians. Infections were detected in 1335 (6.4%) of 21004 patients (71% of 29 401 attendees) screened at the central STD clinic from 1988 to 1991. STD clinic yields suggest a male: female ratio of 1.08:1 (95% confidence intervals = 1.05:1–1.11:1), with 46% of infections in males and 67% of infections in females being asymptomatic. For both males and females, infection rates were highest in 15–19-year-olds and decreased with increasing age, but were not independently related to marital status. The statewide epidemiological pattern was probably distorted in medical reports because of selection biases in testing (89% of tests performed by non-STD clinicians were on females) which resulted in decreased detection in asymptomatic females, symptomatic and asymptomatic males, married persons and unmarried young persons (15–19-year-old females and 15–24-year-old males) by private practitioners. A cost-effective method for increased detection of chlamydial infection in undertested groups (particularly of asymptomatic unmarried males aged 15–24) will be required to control transmission of chlamydial infection in South Australia. Increased detection in young married persons is also desirable.
Sexually Transmitted Diseases and Sexual Behaviour as Risk Factors for HIV-2 Infection in Bissau, Guinea Bissau
Authors: Nauclér Anders , Albino Paolo , Da Silva Agusto Paolo , Biberfeld Gunnel
Published: January 2017

Patients enrolled in a hospital-based case control study ( n = 1009) and a follow-up study ( n = 130) of HIV-2 infection in Bissau were investigated with regard to sexual behaviour and sexually transmitted diseases (STD). A history of genital ulcer was more frequent in HIV-2 infected male patients (46.4%, 13 out of 28) than in seronegative male patients (17.9%, 7 out of 39) ( P = 0.05). Serological evidence of a previous syphilitic infection was significantly related to HIV-2 infection (23%, 12 out of 52, of HIV-2 seropositive patients had a positive Treponema pallidum haemagglutination test compared with 7.1%, 5 out of 70, of seronegative patients, P = 0.025) and was equally frequent in men and women. There was no significant difference in number of non-marital sexual partners and frequency of intercourse between HIV-2 seropositive and seronegative individuals. The seroprevalence of HIV-2 infection was significantly higher among patients with a monogamous marriage, 23.1% (59 out of 255) among males and 31.3% (64 out of 204) among females, than among patients with an officially polygamous marriage, 10.3% (8 out of 77) among males and 11.8% (7 out of 59) among females ( P = 0.025 for males and 0.005 for females). Infection-control measures directed at patients with STD should be promoted in Guinea-Bissau. Further research on sexual behaviour and attitudes is needed.
An Audit of Treatment of Genital Warts: Opening the Feedback Loop
Authors: Reynolds M , Murphy M , Waugh M A , Lacey C J N
Published: January 2017

An audit of the treatment of patients (100 men and 90 women) presenting with a first episode of anogenital warts to the Genitourinary Medicine Department at Leeds General Infirmary was performed. Treatment of patients was monitored for a period of 6 months from the time of presentation. The management of patients with genital warts lacked a clearly defined strategy and treatment was unselective and poorly monitored. Excluding patients who defaulted, at follow-up 44 (44%) men and 36 (38%) women still had genital warts at 3 months. Of those patients clear of warts at 3 months, the mean time to remission for men and women was 7.1 and 8.3 weeks respectively. Podophyllin 25% in tincture of benzoin was by far the predominant therapeutic modality used. A total of 96 (96%) men and 76 (84%) women received treatment with podophyllin. Both male and female patients had a mean of 5 treatments with podophyllin 25% (range 1–19 and 1–12 respectively). Physical methods of treatment i.e. cryotherapy and electrocautery, were underutilized, both as primary therapies and when topical agents had failed. Patients saw an average of 3 (range 1–7) doctors over the course of their treatment. Patients with warts affecting 2 or more sites, male patients with anal/perianal warts, and female patients with cervical and vaginal warts had higher failure rates from treatment at 3 months. On the basis of these findings, specific treatment protocols for the management of anogenital warts have been devised.
Causes of Weight Loss in Human Immunodeficiency Virus Infection
Authors: Summerbell C D , Perrett J P , Gazzard B G
Published: January 2017

The medical records of all 420 patients attending an outpatient clinic between June 1990 and June 1991 were retrospectively reviewed for causes of weight loss. Of the 121 (29%) patients who had lost weight, the majority had a clear contributing cause; opportunistic infections ( n = 57), psychosocial factors ( n = 20), drug related problems ( n = 9). Unexplained weight loss ( n = 35) was more likely to have occurred in those patients with a better preserved immune system and most of these had symptoms suggestive of an unconfirmed infection or had local oral lesions associated with a loss of appetite. Unexplained weight loss associated with HIV infection is uncommon.
HIV Infection in the Caribbean
Authors: Wheeler V W , Radcliffe K W
Published: January 2017

The Caribbean is a multi-ethnic region with many different cultural differences. The majority of the population is of African descent, but there are also other ethnic groups present such as Indians, Chinese, Syrians and Europeans. The Caribbean region is influenced by countries such as the USA, Great Britain, France and Holland. The countries of the Caribbean have a serious problem with HIV infection and AIDS. The epidemiology of HIV infection in this region, is different from most other parts of the world in that the mode of spread does not easily fit into any of the three WHO patterns. This review shows that the infection initially started in the homosexual/bisexual community, but since then, it has moved to the heterosexual population and this form of contact is now the main mode of transmission of the virus. The Governments of the Caribbean countries have realized the extent of the problem and have taken measures to try to control the epidemic.
HIV Testing and Prevalence in Pregnancy in Edinburgh
Authors: Johnstone F D , Brettle R P , Burns S M , Peutherer J , Mok J Y Q , Robertson J R , Hamilton B , Tappin D M
Published: January 2017

The objective was to study the changes in pregnancy HIV prevalence with time. Data were collected from multiple sources to provide a comprehensive record of all HIV seropositive pregnant women identified in the Edinburgh area (Scotland) until December 1992.

There were 177 pregnancies in 108 HIV seropositive identified women. Risk factors were injection drug use (79% of pregnancies) and a known HIV seropositive injection drug-using partner (16%). Prevalence has decreased for Edinburgh City women from 0.5% of all pregnancies in 1986 to 0.1% in 1992; It was higher for induced abortion (0.6%) than for delivery (0.2%). HIV testing in pregnancy has declined. Comparison with unlinked anonymized testing showed that in 1990–1991, 20/22 seropositive women were known. In 1992, only 3 of 10 seropositive pregnancies were identified. The cohort initially infected by exposure to a ‘drug related’ risk factor between 1983 and 1985 may have increasingly finished childbearing, deliberately decided against pregnancy because of HIV status, and declined because of death, illness and emigration from the area, There may not have been major early tertiary heterosexual spread; however, data from 1992 suggest that this could now be impacting on pregnancy prevalence. Local testing policies have not adapted to this possible change.
Low and Stable Prevalence of HIV among Drug Injectors in Glasgow
Authors: Taylor A , Frischer M , Green S T , Goldberg D , McKeganey N , Gruer L
Published: January 2017

The first HIV-positive diagnosis among injecting drug users (IDU) in Glasgow was made in 1985. By the end of 1987 prevalence among IDU receiving voluntary attributable tests was 4.8%. Since 1990, an annual cross-sectional survey of HIV prevalence and risk behaviours among 500 current Glasgow IDU has provided a more representative sample. Anonymously-tested saliva samples obtained from respondents revealed prevalence rates of 1.8%, 1.2% and 1.0% in 1990, 1991 and 1992 respectively. Siince 1987 a wide range of measures aimed at reducing HIV-related risk behaviour among IDU has been introduced and maintained in Glasgow. Against this background, there is evidence that IDU in the city have reduced their risk behaviours. The findings reported here suggest that implementing harm-reduction measures when prevalence is low may inhibit the rapid dissemination of HIV.
The Association of Human Papillomavirus Infection with Balanoposthitis: A Description of Five Cases with Proposals for Treatment
Authors: Birley H D L , Luzzi G A , Walker M M , Ryait B , Taylor-Robinson D , Renton A M
Published: January 2017

The features and clinical course of chronic balanitis in 5 patients are presented. In each case, histological examination of a cutaneous biopsy sample showed pronounced features of human papillomavirus (HPV) infection. In addition, HPV DNA was demonstrated in each biopsy specimen by a polymerase chain reaction and was found to be type 6 by Southern blot hybridization in 4 of the cases.

Although the association of histological features of HPV infection with balanitis does not prove that HPV is causal, the failure to find other causes, the prolonged and distressing symptoms, and the ineffectiveness of topical steroids in improving symptoms, all suggest the importance of HPV infection. While effective treatment needs to be sought and developed, the response of one patient to oral isotretinoin suggests that this agent may be appropriate for a larger trial.
Mathematical Modelling and Field Measurements of Nitrogen Oxides in Metropolitan Areas
Authors: Elkotb M.M. , Elbahar O.M.F. , Ahmed T.A. Abdou , Abou-Arab T.W.
Published: January 2017

A mathematical model for the prediction of pollutant emissions from motor vehicles is presented. The model is based on the numerical solution of the three-dimensional equation representing the mass conservation of dilute diffusing species. The variation of wind speed and eddy diffusivity with height is taken into consideration. The three-dimensional diffusion equation is solved numerically. The numerical procedure involves the discretization of the partial differential equation using the finite volume approach. The resulting set of discretization equation is solved iteratively using a fully implicit solution procedure. Furthermore, field measurements of the concentrations of nitrogen oxide in the downtown area of Cairo were conducted. For this purpose, a mobile air pollution laboratory fitted with gas analyzers, particulate matter sampler and equipment for the measurement of wind speed and direction has been used. This laboratory is also fitted with data recording and monitoring facility. The mathematical model is tested by comparing the computed pollutant concentrations with the experimental data obtained from the field measurements in the Cairo Metropolitan Area.
Lay Perspectives concerning Global Climate Change in Sweden
Authors: Löfstedt Ragnar E.
Published: January 2017

This paper discusses the effects of the ongoing debate concerning the greenhouse effect in Sweden on the general public in the town of Umeå. Issues that are seen to be of importance include: 1. the people's inability to disassociate the greenhouse effect from the ozone hole debate, 2. the equity issues connected to the region, 3. people's attitudes toward the greenhouse effect, and 4. the solutions considered to be the best for solving the problem of global climate change. These issues are based on twenty four person to person in-depth interviews which took place during July and August of 1990.
Nuclear Power: The Environmental Benefits
Authors: Hawley R. , Turner W.
Published: January 2017

There are many environmental benefits arising from the generation of electricity from nuclear power. These are accompanied by a minimal detrimental environmental impact, which is strictly regulated and monitored to a far greater degree than any other comparable industry. Because it does not produce greenhouse gases or acid rain emissions, the generation of electricity from nuclear energy is a vital component of a sustainable energy future for our planet.
Risks of Seven UK Electricity Generation Options Part II: The Risk of Large-Scale Accidents
Authors: Roberts L.E.J. , Ball D.J.
Published: January 2017

Large-scale accidents cause great social disruption and public alarm and the risks of such accidents must be considered together with those arising during normal operation (Ball and Roberts, 1995). The record of severe accidents in the technologies that contribute to electricity generation is summarised; the UK figures compare favourably with the average in the world. Since such events are rare, future risks have to be assessed by applying the methods of risk analysis to individual installations. Risks of severe accidents should reduce further as modern methods of risk analysis and safety management are developed and applied.
Energy and the Die Casting Industry
Authors: Griffiths A. J. , Dunne C. , Lloyd B.
Published: January 2017

This paper focuses the use of energy within the die cast industry. This classical primary melting sector is a typical “feast or famine” industry. Aluminium and zinc are the primary metals and are in the top four for the volume produced. Energy costs vary from 3 to 8 percent of the total product cost, being the third highest cost within the industry. The specific energy index for die casting of aluminium varies from 44 to 65 GJ/tonne and for zinc the index ranges from 30 to 60 GJ/tonne. Case studies have been used to highlight the energy potential for this industry. It was found that electricity accounts for over 60 percent of the total energy cost and that within the energy chain of manufacture, yield has a significant influence. It was further identified that non process energy consumption was relatively high, amounting to 30% of the total. Energy management structures within the industry was variable, being at best, a part time function of a manager. Considerable energy savings can be achieved and the paper highlights areas within the process route where more detailed investigations can have a dramatic impact on energy cost.
Biogas – A Promising Energy Supplement for Nigerian Economic Growth and Environment Protection
Authors: Umar Bobboi
Published: January 2017

The problem of energy crisis continues to reverberate in many of the developing countries. In Nigeria, the majority of families living in villages and small towns depend on wood as their domestic fuel. This is because other conventional fuels such as kerosene, electricity and LPG are costly, unreliable or unavailable. Because of the serious environmental effects fuelwood harvesting poses, other cheaper, environment-friendly renewable energy sources such as biogas should be sought. This short review paper explores the potentials for and feasibility of biogas production in Nigeria where the technology is not yet adopted, and recommends how to make it viable in the country.
The Effects of Reducing the Motor Fuels Excise Tax on Agriculture in the United States
Authors: Uri Noel D. , Boyd Roy
Published: January 2017

The analysis in this paper examines the impact of reducing the federal excise tax on gasoline and diesel fuel on the United States economy in general and the agricultural sectors in particular. The analytical approach used in the analysis consists of a computable general equilibrium model composed of fourteen producing sectors. fourteen consuming sectors, six household categories classified by income and a government. The effects of a 4.3 cents per gallon reduction in the excise tax on gasoline and diesel fuel in prices and quantities are examined. The results suggest. for example, a decrease in the tax would result in higher output by the producing sectors (by about $2.86 billion), a decline in output in the agricultural sectors of about 0.01 percent or $18.4 million. an expansion in the consumption of goods and services (by about $3.84 billion), and an increase in welfare (by about $3.59 billion). The government would realize a decrease in revenue of about $2.37 billion. When subjected to a sensitivity analysis. the results are reasonably robust with regard to the assumption of the values of the substitution elasticities.
Consumption Target Values for Electrical Appliances in Switzerland
Authors: Gruber Edelgard , Ostertag Katrin , Bush Eric
Published: January 2017

Target values for the power consumption of electrical equipment have been laid down in Switzerland in collaboration with the industry as a new type of energy policy instrument. As a general rule, 95% of the equipment sold is required to comply with these target values by the set deadlines, otherwise the government is authorised to issue admission restrictions. An evaluation of these measures has indicated that manufacturers and importers displayed a motivated and constructive approach during these negotiations and have set out to meet the consumption values. Although the targeted sales figures for efficient appliances have not yet been reached in any of the equipment categories, it can be stated that a step has certainly been taken in the right direction. In combination with the effects of the “Energy 2000 Label”, the stipulation of consumption target values can already be described as a successful move, especially in the fields of office and electronic entertainment equipment.
The Implications of the Adoption of Alternative Production Practices on the Estimation of Input Productivity in Agriculture
Authors: Kim C.S. , Sandretto C. , Uri N.D.
Published: January 2017

This paper explores the implications of a misspecification of the production function on the use of factor inputs in the context of the adoption of an alternative production practice (a technological innovation) designed to mitigate the impact of agricultural production on human health and the environment. It is demonstrated that if the level of use of some inputs is considered rather than their consumptive use (i.e., the actual amount used by a plant), the productivity of the input is inaccurately measured. It is also demonstrated that an aggregate production function approach can lead to overestimation of the value of the marginal product of an input due to the frequently implicit assumptions that the output supply, output demand, and fertilizer demand are infinitely price elastic. The implications of the results are important for determining the optimal use of inputs such as fertilizer and pesticides which have known adverse impacts on the environment and human health.
Oxygenates in Gasoline and Their Influence on Air Quality
Authors: Parsons Barney , Westwood John
Published: January 2017

This paper summarises the results of a major study published in January 1997. It fore-casts world demand for oxygenates over the period 1996 to 2000 and considers the factors impacting on the market in the light of the results of the European Auto-oil programme and changes in the two other major gasoline markets of the USA and Japan.
Some implications for quantitative risk assessment if hormesis exists
Authors: Sielken Robert L , Stevenson Donald E
Published: January 2017

The existence of hormesis should impact quantitative risk assessment in at least seven fundamental ways. (1) The dose-reponse models for bioassay and epidemiological data should have greater flexibility to fit the observed shape of the dose-response data and no longer be forced to always be linearly increasing at low doses. (2) Experimental designs should be altered to provide greater opportunity to identify the hormetic component of a dose-response relationship. (3) Rather than a lifetime average daily dose or its analog for shorter time periods, dose scales or metrics should be used that reflect the age or time dependence of the dose level. (4) Low-dose risk characterization should include the likelihood of bene-ficial effects and the likelihood that a dose level has reasonable certainty of no appreciable adverse health effects. (5) Exposure assessments should make greater efforts to characterize the distribution of actual doses from exposure rather than just upper bounds. (6) Uncertainty characterizations should be expanded to include both upper and lower bounds, and there should be an increased explicit use of expert judgement and weight-of-evidence based distributional analyses reflecting more of the available relevant dose-response information and alternative risk characterizations. (7) Risk should be characterized in terms of the net effect of a dose on health rather than a dose's effect on a single factor affecting health - for example, risk would be better expressed in terms of mortality from all causes combined rather than a specific type of fatal disease.
Implications of hormesis for biomedical aging research
Authors: Johnson Thomas E , Bruunsgaard Helle
Published: January 2017

Rather than being an exception, non-linearity between dose and response are the rule in biological systems. It might even be anticipated that at some doses a response opposite to that seen at high doses could be elicited (hormesis). Such non-linearity with dose has multiple implications for numerous aspects of biomedical research on aging and for experimental design. Moreover, the implications of such non-linearity are such that governmental regulatory activities and other areas of public health administration will be affected to a large extent once hormesis is widely recognized. The implications with regard to environmental intervention and subsequent regulatory decisions will certainly profoundly affect the political process, as well.
Agricultural implications of pesticide-induced hormesis of insects and mites
Authors: Morse Joseph G
Published: January 2017

Resurgence of pest insects and mites and secondary pest outbreaks are commonly observed following pesticide applications on agricultural commodities. Reduction of natural enemy populations is the major factor blamed for these phenomena but insect or mite hormesis is a second, often overlooked factor which may be partially responsible. A major impact of hormesis is that it often leads to the need for additional pesticide treatments and can result in a spiralling increase in the use of pesticides, a term labelled in entomological literature as the `pesticide syndrome'.
A prospective study of acute poisonings in Finnish hospital patients
Authors: Lapatto-Reiniluoto Outi , Kivistö Kari T , Pohjola-Sintonen Sinikka , Luomanmäki Kimmo , Neuvonen Pertti J
Published: January 2017

1 We have carried out a prospective study of all adult patients presenting with acute poisoning during one month to the Helsinki University Central Hospital (Meilahti Hospital).

2 Two hundred and twenty-six cases of acute poisoning (113 males and 113 females) presented to the emergency department. Most cases in both men (66%) and women (67%) involved alcohol. As to drugs, psychotropic agents predominated in both men and women. The frequency of patient presentation peaked between 7 p.m. and 9 p.m. and was lowest between 8 a.m. and 10 a.m. In most cases, the delay from ingestion of the poison to presentation was longer than 4h.

3 The clinical status of the patients on arrival was generally good; more than half (55%) of them were fully awake. Serious symptoms (e.g. unconsciousness, insufficient respiration necessitating intubation, aspiration, convulsions or hypotension) occurred in 15% of the presentations. There were no fatalities.

4 One hundred and thirty-five patients (60%) received at least one 50-g dose of activated charcoal. However, charcoal was given in 86% of the cases of drug poisoning. Gastric lavage was performed in 112 cases (50%), and 106 cases (47%) involved both gastric lavage and administration of charcoal. Twenty-one patients received antidotes (flumazenil, calcium gluconate or naloxone) and three patients were hemodialysed.

5 Of the 226 cases, 142 (63%) were managed solely in the emergency department. Of the 84 cases admitted to the hospital, eight had to be managed in the intensive care unit. Almost all patients (94%) were discharged within 24 h.

6 In this survey on 226 consecutive cases of acute poisoning, about two-thirds of the cases involved alcohol, while the most common drugs taken were psychotropic agents. The poisoning was mild in the great majority of the cases. Activated charcoal was generally administered in all but trivial cases of drug poisoning.
Oncogenicity studies of piperonyl butoxide in rats and mice
Authors: Butler W H , Gabriel K L , Osimitz T G , Preiss F J
Published: January 2017

1 The oncogenicity of Piperonyl butoxide (PBO) has been studied in the mouse and rat. CD-1 mice were administered PBO in the diet at target doses of 0, 30, 100 and 300 mg/kg/day for 79 weeks and Sprague - Dawley rats 0, 30, 100 and 500 mg/kg/day for 104/105 weeks.

2 At termination of the study in the mouse there was evidence of increased liver weights and an increased incidence of eosinophilic adenomas at 100 and 300 mg/kg/day in males and 300 mg/kg/day in females.

3 In rats there was increased liver weights at 100 and 500 mg/kg/day associated with hepatocyte hypertrophy in both male and female rats. There was no increased incidence of neoplasia at any site. Hyper-trophy and hyperplasia of thyroid follicles was observed at 500 mg/kg/day in both sexes.

4 The observations reflect the expected changes related to the induction of the mixed function oxygenase group of enzymes. In the mouse the increased incidence of eosinophilic adenomas is not considered relevant for human risk evaluation.
A comparison of the efficacy of new asymmetric bispyridinium oxime BI-6 with other oximes (obidoxime, HI-6) against soman in rats
Authors: Kassa J
Published: January 2017

1 The influence of three oximes (obidoxime, HI-6 and the new asymmetric bispyridinium oxime BI-6) in combination with atropine on soman-induced cholinergic and stressogenic effects in rats was studied.

2 The oxime BI-6 produced significantly higher reactivation of soman-inhibited blood and diaphragm cholinesterases than obidoxime. On the other hand, its reactivating effect was not so high as the effect of the oxime HI-6.

3 There were not significant differences in the reactivation of soman-inhibited brain acetycholinesterase among all three oximes tested.

4 The influence of the oxime BI-6 on soman-induced stressogenic effects was greater than the antistressogenic effects of HI-6 or obidoxime at 1 h or 3 h following soman poisoning.

5 These findings confirm that the oxime BI-6 has no definite advantages over HI-6 in the antidotal treatment of soman poisoning but BI-6 is significantly more effective in rats than obidoxime, one of the oximes presently in use.
Influence of ranitidine on the morphine-3- glucuronide to morphine-6-glucuronide ratio after oral administration of morphine in humans
Authors: Aasmundstad Tor A , Størset Per
Published: January 2017

1 In humans morphine is metabolised to morphine-3- glucuronide (M3G) which possess no opioid activity, and morphine-6-glucuronide (M6G) which is a potent opioid receptor agonist that probably contribute to the desired as well as toxic effects of morphine.

2 In order to investigate the possible effect of ranitidine on morphine glucuronidation indicated by clinical studies and later confirmed in vitro, a double blind cross-over study on eight human volunteers administered oral morphine plus ranitidine or placebo was conducted.

3 Urine was collected in fractions for 24 h. Serum and urine samples were prepared by solid phase extraction andmorphine, M3G and M6G were quantified by HPLC.

4 Ranitidine significantly reduced the individual serum M3G/M6G ratio, and tended to increase the serum AUC(0 - 90) of morphine. In contrast, ranitidine had no significant effect on the urinary M3G/M6G ratio. The urinary recovery of morphine or morphine glucuronides was unaffected by ranitidine.

5 Possible explanations to the apparent incongruity between the serum and urine data are discussed.
Risk management for plausibly hormetic environmental carcinogens: The case of radon
Authors: Bogen Kenneth T , Layton David W
Published: January 2017

Risk management typically involves efforts to reduce human exposures by establishing regulations that limit the concentration of the substance in environmental media. In cases where a substance is widely used in commerce or is naturally occurring in the environment, compliance costs can be substantial because of nationwide requirements to add expensive control technologies. Uncertainties in a dose-response function further impact risk management decisions because they may correspond to large differences in health benefit per unit exposure reduction. These problems are highlighted in the case of plausibly hormetic environmental carcinogens, for which a linear-no-threshold (LNT) dose-response model has been the traditional regulatory default assumption. In this case, model uncertainty is pivotal, and risk management is consequently inherently controversial. However, marginal cost functions that arise for plausibly hormetic carcinogens are expected to possess a common analytic feature that may be particularly useful for this type of risk management problem. Specifically, marginal cost functions in this context are expected to have roots reflecting contaminant concentration values above which regulatory goals may be optimally placed subject to cost constraints. Here we illustrate this heuristic feature in the case of residential radon, using both a LNT model and a biologically plausible hormetic model to predict associated risks of lung cancer mortality.
An overview of group sequential methods in longitudinal clinical trials
Authors: Spiessens Bart , Lesaffre Emmanuel , Verbeke Geert , Kim KyungMann , DeMets David L
Published: January 2017

During the last decade, several papers have been published on group sequential methods in general and on sequential longitudinal clinical trials in particular. This paper gives an overview of the proposed methods, emphasizing longitudinal clinical trials. Furthermore, it tries to answer some practical questions that may arise during the conduct of interim analyses in longitudinal trials. Simulations have been carried out to obtain insight in these practical considerations.
Partitioning methods for multifactorial risk attribution
Authors: Land Matthias , Vogel Christine , Gefeller Olaf
Published: January 2017

The epidemiological problem of risk attribution in the framework of multiple exposures has been the subject of intensive research activities in the last decade. In particular, partitioning methods have been developed to define new multidimensional measures of attributable risk putting the task of quantifying a proportion of disease events in a population that can be ascribed to the adverse health effects of certain risk factors into a multifactorial perspective. The parameters generalize the concept of attributable risk to different multifactorial frameworks in which multiple exposures might be arranged in hierarchically ordered classes or in equally ranking groups. Partitioning methods are reviewed and differences between the multifactorial variants of attributable risk are illustrated by a component causes model.
Multilevel models for meta-analysis, and their application to absolute risk differences
Authors: Thompson Simon G , Turner Rebecca M , Warn David E
Published: January 2017

Meta-analysis can be considered a multilevel statistical problem, since information within studies is combined in the presence of potential heterogeneity between studies. Here a general multilevel model framework is developed for meta-analysis to combine either summary data or individual patient outcome data from each study, and to include either study or individual level covariates that might explain heterogeneity. Classical and Bayesian approaches to estimation are contrasted. These methods are applied to a meta-analysis of trials of thrombolytic therapy after myocardial infarction. Subgroups within the trials were available, categorized by the time delay until treatment, so that a three-level random effects model that includes time delay as a covariate is proposed. In addition it was desired to represent the treatment effect as an absolute risk reduction, rather than the conventional odds ratio. We show how this can be achieved within a Bayesian analysis, while still recognizing the binary nature of the original outcome data.
Estimating effects of latent and measured genotypes in multilevel models
Authors: van den Oord Edwin JCG
Published: January 2017

Multilevel modelling is a data analysis technique for analysing linear models in samples with a hierarchical or clustered structure. Clustered data are often present in genetic research where family members may either be required or serve a methodological purpose to study hereditary factors. These samples imply a natural hierarchy because genetically related individuals are grouped within families. We first demonstrate the use of multilevel modelling to study latent genetic and environmental components of variance in extended families where subjects may be related as twins, full siblings, half siblings, or cousins. Next, measured genotypes are included to estimate locus effects. Because the model accounts for the clustering of observations by estimating a random intercept at the family level, it tests for genotype effects on the phenotype within families so that possible population stratification effects cannot cause false positive results. Several extensions are discussed such as testing for genotype-environment interactions, analysing different types of response scales, or tailoring the model to other sample structures. To illustrate the approach we used birth weight data of 5562 children from 3643 fathers from 3186 mothers in 2873 extended families to which simulated genotypes of a hypothetical locus were added.
Multilevel models for censored and latent responses
Authors: Rabe-Hesketh Sophia , Yang Shuying , Pickles Andrew
Published: January 2017

Multilevel models were originally developed to allow linear regression or ANOVA models to be applied to observations that are not mutually independent. This lack of independence commonly arises due to clustering of the units of observations into ‘higher level units’ such as patients in hospitals. In linear mixed models, the within-cluster correlations are modelled by including random effects in a linear model.

In this paper, we discuss generalizations of linear mixed models suitable for responses subject to systematic and random measurement error and interval censoring.

The first example uses data from two cross-sectional surveys of schoolchildren to investigate risk factors for early first experimentation with cigarettes. Here the recalled times of the children’s first cigarette are likely to be subject to both systematic and random measurement errors as well as being interval censored. We describe multilevel models for interval censored survival times as special cases of generalized linear mixed models and discuss methods of estimating systematic recall bias.

The second example is a longitudinal study of mental health problems of patients nested in clinics. Here the outcome is measured by multiple questionnaires allowing the measurement errors to be modelled within a linear latent growth curve model. The resulting model is a multilevel structural equation model. We briefly discuss such models both as extensions of linear mixed models and as extensions of structural equation models. Several different model structures are examined.

An important goal of the paper is to place a number of methods that readers may have considered as being distinct within a single overall modelling framework.
Simple linear regression with interval censored dependent and independent variables
Authors: de Lima Taga Marcel F , Singer Julio M
Published: January 2017

We consider a simple linear regression model that accommodates situations where both the dependent and the independent variables are interval censored. We obtain maximum likelihood estimators of its parameters and compare their performance with that of estimators derived under ordinary linear regression models. We also develop prediction intervals for the response and illustrate the results with data from an audiometric study designed to evaluate the possibility of prediction of behavioural thresholds from physiological thresholds.
Variable selection in rank regression for analyzing longitudinal data
Authors: Fu Liya , Wang You-Gan
Published: January 2017

In this paper, we consider variable selection in rank regression models for longitudinal data. To obtain both robustness and effective selection of important covariates, we propose incorporating shrinkage by adaptive lasso or SCAD in the Wilcoxon dispersion function and establishing the oracle properties of the new method. The new method can be conveniently implemented with the statistical software R. The performance of the proposed method is demonstrated via simulation studies. Finally, two datasets are analyzed for illustration. Some interesting findings are reported and discussed.
Maximum likelihood analysis of generalized linear models with missing covariates
Authors: Horton Nicholas J , Laird Nan M
Published: January 2017

Missing data is a common occurrence in most medical research data collection enterprises. There is an extensive literature concerning missing data, much of which has focused on missing outcomes. Covariates in regression models are often missing, particularly if information is being collected from multiple sources. The method of weights is an implementation of the EM algorithm for general maximum-likelihood analysis of regression models, including generalized linear models (GLMs) with incomplete covariates. In this paper, we will describe the method of weights in detail, illustrate its application with several examples, discuss its advantages and limitations, and review extensions and applications of the method.