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Male infertility or subfertility is frequently associated with disruption of the hypothalamic-pituitary-testis axis events, like secondary hypogonadism. However, little is known how this condition affects the proteomic composition of the epididymal fluid. In the present study, we evaluated the proteomic changes in the cauda epididymal fluid (CEF) in a swine model of secondary hypogonadism induced by anti-GnRH immunization using multidimensional protein identification technology. Seven hundred and eighteen proteins were identified in both GnRH-immunized and control groups. GnRH immunization doubled the number of proteins in the CEF, with 417 proteins being found exclusively in samples from GnRH-immunized boars. CEF from GnRH-immunized boars presented an increase in the number of proteins related to cellular and metabolic processes, with affinity to organic cyclic compounds, small molecules, and heterocyclic compounds, as well changed the enzymatic profile of the CEF. Also, a significant increase in the number of proteins associated to the ubiquitin-proteasome system was identified in CEF from GnRH-immunized animals. These results bring strong evidence of the impact of secondary hypogonadism on the epididymal environment, which is responsible for sperm maturation and storage prior ejaculation. Finally, the differently expressed proteins in the CEF are putative seminal biomarkers for testicular and epididymal disorders caused by secondary hypogonadism.

Alpine ski racing is known as a high-risk sport; however, little is known on the health problems occurring at youth level. The purpose of this study was to investigate the prevalence of health problems in youth competitive alpine skiers with respect to sex, age, and season differences, to describe their severity and location and to assess the influence of biological maturation. Over a 12-month period, 155 youth competitive alpine skiers around the growth spurt were prospectively monitored for health problems using the Oslo Sports Trauma Research Centre (OSTRC) questionnaire. These data were verified by supplemental interviews at the end. Biological maturation was estimated by a non-invasive, anthropometric-based assessment method. During competition season, 42.2% of the skiers suffered from health problems and 19.8% reported their problem being substantial. Females had significantly higher rates of acute and overuse injuries compared to males, while there was no sex difference in duration, severity, and time loss. Skiers of the category U15 showed higher prevalence of acute and overuse injuries than U14 skiers. During preparation season, health problem prevalence was substantially lower. The knee was found to be the most affected body part for both acute and overuse injuries. There was a direct association between the offset to the age at peak height velocity (APHV) and the occurrence and severity of acute injuries. In conclusion, youth competitive alpine skiers suffer from a large number of health problems. Since sex, age, and biological maturation are important, effective injury prevention should already start before reaching the APHV.

Numerous studies investigated the association between dynamic knee valgus and injury risk in post-pubertal and elite athletes; however, normative reference scores for competitive alpine skiers and observations on the development process throughout and beyond athletes' growth spurt are lacking. Thus, the aim of this study was to describe the dynamic knee valgus of competitive alpine skiers during drop jump landings (DJ) and single-leg squats (SLS) with respect to sex, sportive level, and biological maturation. Thirty-seven elite and 104 youth competitive alpine skiers around the growth spurt (U15) were examined for their maximal medial knee displacement (MKD) during DJ and SLS by a marker-based 3D motion analysis evaluating dynamic knee valgus. Additionally, skiers' age, anthropometry and biological maturation were assessed. MKD of youth and elite alpine skiers during DJ was comparable and did not improve with increasing training age. Female U15 skiers (on average further matured) had significantly larger MKD values during DJ than male U15 skiers (less matured) (P

Aims and objectives To examine patients’ perceptions of being asked about their sexual orientation and gender identity in the healthcare setting. Background Health disparities exist in the lesbian, gay, bisexual and transgender population, but further research is needed to better understand these disparities. To address this issue, experts recommend the routine collection of sexual orientation and gender identity data in health care. Nurses on the front line of patient care play a key role in the collection of these data. However, to enable nurses to conduct such assessments it is important to understand the perspective of the patients on being asked about their sexual orientation and gender identity in a healthcare setting. Design An integrative review was conducted using the methodology proposed by Whittemore and Knafl (Journal of Advanced Nursing, 2005, 52, 546). Methods Six electronic databases were searched, and two reviewers independently reviewed papers for inclusion. Papers were included if they were empirical studies, peer-reviewed papers or reports, assessing patient perspectives on discussing sexual orientation and gender identity in the healthcare setting. Results Twenty-one relevant studies that met the inclusion criteria were identified. A majority of the studies indicated patients’ willingness to respond to, and a perceived importance of, questions about sexual orientation and gender identity. However, fears of homophobia and negative consequences hindered willingness to disclose this information. Conclusions This review indicates that in most cases patients are willing to answer routine questions about their sexual orientation in the healthcare setting and perceive them as important questions to ask. Relevance to clinical practice The findings of this review have implications for nurses looking to incorporate questions about sexual orientation into their routine patient assessment. The findings indicate that care providers need to be mindful of heteronormative assumptions and take steps to ensure they are knowledgeable about lesbian, gay, bisexual and transgender health.

Cryptococcosis, caused by Cryptococcus spp., is an invasive fungal infection of the central nervous system, associated with high mortality, affecting mainly immunocompromised patients. Due to the development of resistance to the current therapy, there is an urgent need for less toxic and more effective antifungal agents. In this study, we describe the antifungal activity against Cryptococcus spp. of an aqueous seed extract from Allamanda polyantha (ASEAP) and two iridoids, plumieride and plumieridine, isolated from this extract with an antifungal activity. The capsule formation and the morphological alterations were evaluated using fluorescent microscopy. The cytotoxic activity was also investigated. The minimal inhibitory concentration (MIC) values of ASEAP for Cryptococcus gattii were 70 and 36 µg/ml (for the R265 and R272 strains, respectively) and 563 µg/ml for Cryptococcus neoformans H99. ASEAP inhibited C. neoformans H99 capsule formation, an important virulence factor, and decreased the cell body size for both the C. gattii strains. H99 cells also presented morphological alterations, with defects in bud detachment and nuclear fragmentation. Plumieride and plumieridine presented higher MIC values than ASEAP, indicating that other compounds might contribute to antifungal activity and/or that combination of the compounds results in a higher antifungal activity.

Quantification of basic demographic parameters such as survival rates and cause-specific mortality is important for effective species management. We conducted a 4-year study (during May 2005-June 2009) of elk Cervus canadensis calf survival and cause-specific mortality in Pennsylvania, USA. We captured and radio-collared 93 elk calves ≤ 7 days old and monitored them weekly to detect mortality and cause of death. Of the 93 radio-collared elk calves, 15 (16%) died during our study. Despite high black bear Ursus americanus and coyote Canis latrans densities, none of the mortalities were the result of predation. Causes of death included poaching (N = 3), legal harvest (N = 2), road kill (N = 2), pneumonia (N = 1) and rumen acidosis (N = 1). We were unable to determine the cause of mortality for six of the elk calves; however, predation was eliminated as a possible source of mortality in all unknown cases. Survival probabilities were similar between sexes and among years. Summer survival (birth-31 Oct...

Summary objectives To assess the extent of drug resistance in Uige through molecular genetic analysis and to test whether the dhfr triple mutant alleles present in Angola are of southeast Asian origin. methods Seventy-one samples of blood from children admitted to the Pediatric Emergency Unit of Uige Provincial Hospital in 2004 were screened for resistance mutations at pfcrt, pfmdr1, pfdhfr, pfdhps and pfATPase6. results Mutations in pfcrt (codon76), pfmdr1 (codon86), pfdhfr (codons 51, 59, 108) and pfdhps (codons 436, 437) were common. Among the 66 isolates for which we were able to determine complete genetic information 13.7% carried all seven of these mutations. Flanking microsatellite analysis revealed the triple mutant pfdhfr was derived from the southeast Asian lineage, while the N51I+S108N double mutant pfdhfr alleles are a local origin. pfATPase6 mutations were rare and S769N was not found. conclusion The parasite population of Uige Angola has high frequency mutations in pfcrt, dhfr and dhps associated with resistance to chloroquine and sulphadoxine pyrimethamine, reflecting past reliance on these two drugs which were the mainstay of treatment until recently. Our findings show that drug resistance in Uige has occurred through a combination of local drug pressure and the regional and international dispersal of resistance mutant alleles.

In the course of its work at the grassroots - during disasters (both natural and man-made) in the most backward districts amongst hilly areas as well as tribal areas etc. VHAI has come across children in a range of difficult circumstances. Through this arose the need to enhance the focus on children in our work. However to begin with it is essential to document and understand their situation. We have done this through a comprehensive report entitled: "Seen but not heard: Indias marginalised neglected and vulnerable children." Seen but not heard is as much a report about Indias forgotten children as it is a commentary by these children about the world that adults have bequeathed to them. A world that neglects them tramples on their vulnerability and pushes them to the fringes and very often over the edge. A unique feature of this report is that childrens views share space with adult analysis very much in the spirit of participation enshrined in the UN Convention on the Rights of the Child. (excerpt)

Solution procedures for resource-constrained project scheduling problems are usually validated using simulated data. In many cases, however, a technique that provides quality schedules for simulated data performs poorly on actual projects, because the simulated data might not reflect all the characteristics of real projects. Furthermore, projects in various industries might possess different characteristics. In this paper, we analyze the responses to an empirical study of project managers. The survey was conducted nationwide, and was designed to identify and categorize characteristics of projects in various industries as well as performance measures and constraints. A variety of statistical techniques are used to describe project profiles, ranging from simple descriptive statistics to multivariate analysis. The results demonstrate that while many common project characteristics exist, there are noticeable differences in projects across industries. Some unexpected results are discovered, especially related to project managers' objectives and the constraints they are subject to in establishing schedules. For example, for many project managers, maximizing project quality is more important than other scheduling objectives examined in the literature. Furthermore, results show that project managers are constrained by the availability of labor resources more often than other types of constraints, such as budget or raw materials.

On December 14, 1995, the first public presentation of results of the Transnational Case-Control Study of Oral Contraceptives and the Health of Young Women was made at the winter meeting of the British Pharmacological Society at Brighton. Four weeks later, those results and further analyses were published in the British Medical Journal. There has been much debate about them in Europe and elsewhere. I feel privileged to have been invited to write a Leading Article about the safety of combined oral contraceptives in the British Journal of Clinical Pharmacology. These are personal opinions about the meaning of all the recent pharmacoepidemiological findings. With an historical context as the background I have added my personal reflections as a scientist and a public health doctor. These views do not necessarily reflect the views of my co-investigators.On December 14, 1995, the first public presentation of results of the Transnational Case-Control Study of Oral Contraceptives and the Health of Young Women was made at the winter meeting of the British Pharmacological Society at Brighton. Four weeks later, those results and further analyses were published in the British Medical Journal. There has been much debate about them in Europe and elsewhere. I feel privileged to have been invited to write a Leading Article about the safety of combined oral contraceptives in the British Journal of Clinical Pharmacology. These are personal opinions about the meaning of all the recent pharmacoepidemiological findings. With an historical context as the background I have added my personal reflections as a scientist and a public health doctor. These views do not necessarily reflect the views of my co-investigators. In light of the findings of recent pharmacoepidemiological studies suggesting an association between third generation oral contraceptives (OCs) and cardiovascular and cerebrovascular events, an investigator of one of the studies discusses in this essay why he believes OC use is becoming safer. First generation OCs with a higher estrogenic content (50 mcg) were associated with an increased risk for major cardiovascular and cerebrovascular events. The second and third generation OCs have a much lower estrogen dose, reducing the risk for these events appreciably. Current debate is over whether the occurrence of thrombosis in users of third generation OCs warrants regulatory action. The relative risk for venous thromboembolism (VTE) for users of these OCs in the Transnational Study is small (1.5) albeit statistically significant. This risk may be due to background noise or unavoidable bias. The publication of a meta-analysis of the most recent studies on this association does not describe the methods used. The author of the meta-analysis study ignores the fact that all four studies found weakness of the ratios. Yet, if left unchallenged, the meta-analysis findings can be cut in stone. In the UK, the Committee on Safety of Medicines (CSM) and the Medicines Control Agency warned providers about third generation OCs. The warnings were published based on unpublished findings about VTE. The investigator of one of the pharmacoepidemiological studies offered to show statutory authorities the unpublished findings in confidence if they were concerned. Instead, the authorities issued a letter to all UK physicians informing them about the increased risk of VTE associated with third generation OC use. Other studies have since been reassuring. The US Food and Drug Administration has not taken such drastic steps as the CSM. The resulting public anxiety responding to publicity in the medical and lay press effected early termination of the transnational case control study on OCs and myocardial infarction (MI). So far, it has found much lower risks for MI than those of earlier studies. In conclusion, the medical community needs to begin restoring confidence in OCs.

UNLABELLED The protocol of the Transnational Study on Oral Contraceptives has been published at the outset of the study in order to ensure the correct performance of the study and to ensure the study's scientific integrity. Potential revisions and additions to this protocol had been announced in the prior publication. This article focuses on those points of protocol which have been resolved as practical experience was gathered as well as additional modifications required by practical and scientific considerations. The major alterations are based on exposure prevalences in controls and on power calculations. The low (1.8%) exposure to gestodene among German controls led to the discontinuation of the German component and to the accelerated accession in additional countries. THE CASE control ratio was altered to 3:1 for purposes of economy based on power calculations. Numerous minor points, most addressed in the prior protocol, have been resolved. It is found that these modifications of the study protocol do not impair the study's conduct, its scientific integrity, nor its capability of providing answers to the study question.

The reactivities of engine-out exhaust hydrocarbon (HC) emissions in photochemical smog formation have been determined for three fuels (isooctane, an aromatic blend, and a gasoline) in a single-cylinder, spark-ignited engine. High resolution capillary GC was used to determine the mole fractions of the exhaust hydrocarbon species. Temperature programmed chromatography on a single capillary column was sufficient to separate the major exhaust species. A library of approximately 160 hydrocarbon species was used to identify typically 90–95 % of the HC species present. GC-MS was used selectively to verify peak assignments. The effect of engine operating parameters (fuel-to-air ratio, spark timing, and speed) on reactivity was examined. Engine operating parameters affect both total emissions [g/mile] and the specific atmospheric reactivity [g ozone/g HC emissions] of these emissions. Changing the operating parameters to control total emissions may not be as effective as expected in controlling the total reactivity [g ozone/mile] of the emissions because the specific reactivity can also change simultaneously. Effects of changes in operating parameters differ significantly as the type of fuel is varied. The ability to measure exhaust hydrocarbon species emissions accurately and quickly will increase in importance as reactivity-based emissions standards come into widespread use.

Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance wound healing processes in animal models; however, little is known about the expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds--a pattern of expression closely mirrored by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta 1 mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF-beta 3 is important for maintenance of epidermal differentiation and that an induction of TGF-beta 1 expression is essential for re-epithelialization of human skin wounds. Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.

The kinetics of the reaction of OH radicals with t-amyl methyl ether (TAME) have been reinvestigated using both absolute (flash photolysis resonance fluorescence) and relative rate techniques. Relative rate experiments were conducted at 295 K in 99 kPa (740 torr) of synthetic air using ethyl t-butyl ether, cyclohexane, and di-isopropyl ether as reference compounds. Absolute rate experiments were performed over the temperature range 240–400 K at a total pressure of 4.7 kPa (35 torr) of argon. Rate constant determinations from both techniques are in good agreement and can be represented by k1=(6.32 ± 0.72) × 10−12 exp[(−40 ± 70)/T] cm3 molecule−1 s−1. Quoted errors represent 2σ from the least squares analysis and do not include any estimate of systematic errors. We show that results from the previous kinetic study of reaction (1) are in error due to the presence of a reactive impurity. Results are discussed in terms of the atmospheric chemistry of TAME. © 1993 John Wiley & Sons, Inc.

The collaboration of Dr Neil Poulter and Professor Michael Marmot, both of the Department of Epidemiology and Public Health, University College London Medical School, was crucial for the preparation of the present research protocol. In particular, we made extensive use of a protocol prepared by Dr Poulter and Professor Marmot for the World Health Organization, entitled ‘WHO multicentre case–control study of cardiovascular disease and steroid hormone use’ during the feasibility study carried out in 1991.

The kinetics of the reaction of OH radicals with t-amyl methyl ether (TAME) have been reinvestigated using both absolute (flash photolysis resonance fluorescence) and relative rate techniques. Relative rate experiments were conducted at 295 K in 99 kPa (740 torr) of synthetic air using ethyl t-butyl ether, cyclohexane, and di-isopropyl ether as reference compounds. Absolute rate experiments were performed over the temperature range 240–400 K at a total pressure of 4.7 kPa (35 torr) of argon. Rate constant determinations from both techniques are in good agreement and can be represented by k1=(6.32 ± 0.72) × 10−12 exp[(−40 ± 70)/T] cm3 molecule−1 s−1. Quoted errors represent 2σ from the least squares analysis and do not include any estimate of systematic errors. We show that results from the previous kinetic study of reaction (1) are in error due to the presence of a reactive impurity. Results are discussed in terms of the atmospheric chemistry of TAME. © 1993 John Wiley & Sons, Inc.

In response to growing concerns surrounding the risks of human insulin, we conducted a 13-year historical cohort study of 4925 insulin users less than 40 years of age. This cohort was formed from the population of Saskatchewan, Canada, from 1978–90, using the computerized databases arising from the universal health insurance plan of this Province of 1.1 million inhabitants. Of 101 deaths, 53 occurred within the defined one-month time window of effect. The cohort resulted in 14,600 person-years of exposure to insulin use. The overall rate of death was 3.6 per 1000 person-years of insulin use (95% CI: 2.7–4.6). This death rate remained stable throughout the 13-year study period and did not increase after 1984, the year of introduction of human insulin in Saskatchewan. We found 46 deaths for animal insulin (4.0/1000/year) and 7 deaths for human insulin (2.3/1000/year). Among the latter 7 deaths, 1 death occurred in the group treated solely with human insulin (1.2/1000/year), and 6 deaths in those who were switched from animal to human insulin (2.8/1000/year). These observed differences are not statistically significant. The data from this rapid response pharmacoepidemiological study, which took 8 months to complete, do not support allegations that treatment with human insulin increases the risk of death. They do not however exclude the possibility that human insulin is associated with an elevated risk of fatal or non-fatal hypoglycaemia.

An essential step in the assessment of the relative benefits and risks of a drug's use is the monitoring of its actual utilization in specific populations. However, few studies have documented the extent to which non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for children. We surveyed a sample of 1448 Quebec physicians by mailed questionnaire to estimate approximately how often and for which indications NSAIDs, excluding ASA and acetaminophen, had been prescribed over the past year for children under 16 years of age. The sample included all pediatricians and rheumatologists in the province, and a stratified random sample of general practitioners. A response rate of 81.5 per cent was achieved. The proportion of physicians prescribing NSAIDs varied with speciality and clinical condition. The highest proportions were recorded for dysmenorrhea and juvenile rheumatoid arthritis, followed by tendinitis/bursitis, musculoskeletal trauma and recurrent headaches. Patterns of use were also explored for conditions such as osteochondroses, chronic or recurrent limb and back pain, tooth abscess, and patent ductus arteriosus. These data indicate that NSAIDs are prescribed for conditions for which they are not currently recommended in the pediatric population. Further research is thus required regarding the implications of their use for a wider range of conditions.

The relative rate technique has been used to measure rate constants for the reaction of chlorine atoms with nitro methane, nitro ethane, nitro propane, nitro butane, nitro pentane, ethyl nitrate, isopropyl nitrate, n-propyl nitrate, 2-pentyl nitrate, and 2-heptyl nitrate. Decay rates of these organic species were measured relative to one or more of the following reference compounds; n-butane, ethane, chloroethane, and methane. Using rate constants of 2.25 × 10−10 5.7 × 10−11, 8.04 × 10−12, and 1.0 × 10−13 cm3 molecule−1 s−1 for the reaction of Cl atoms with n-butane, ethane, chloroethane, and methane, respectively, the following rate constants were derived, in units of cm3 molecule−1 s−1: nitro methane

From July 1971, to July 1972, in a large suburban Ontario practice of two family physicians, a randomized controlled trial was conducted to assess the effects of substituting nurse practitioners for physicians in primary-care practice. Before and after the trial, the health status of patients who received conventional care from family physicians was compared with the status of those who received care mainly from nurse practitioners. Both groups of patients had a similar mortality experience, and no differences were found in in physical functional capacity, social function or emotional function. The quality of care rendered to the two groups seemed similar, as assessed by a quantitative "indicator-condition" approach. Satisfaction was high among both patients and professional personnel. Although cost effective from society's point of view, the new method of primary care was not financially profitable to doctors because of current restrictions on reimbursement for the nurse-practitioner services.

Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.