The secular trends in male:female ratio at birth in postwar industrialized countries.

Finnish investigators [Vartiainen et al. Environmental Chemicals and Changes in Sex Ratio: Analysis Over 250 Years in Finland. Environ Health Perspect 107:813-815 (1999)] presented the sex ratio of all newborn babies from 1751 to 1997 in order to evaluate whether Finnish long-term data are compatible with the hypothesis that the decrease in the ratio of male to female births after World War I and World War II in industrial countries is caused by environmental factors. They found an increase in the proportion of males from 1751 to 1920, which was interrupted by peaks in male births during World War I and World War II and followed by a decrease thereafter, similar to the trends in many other countries. The turning point of male proportion, however, preceded the period of industrialization and introduction of pesticides and hormonal drugs. Thus, a causal association between these environmental exposures and this decrease is unlikely. In addition, none of the various family parameters (e.g., paternal age, maternal age, age difference in parents, birth order) could explain the historical time trends. Vartiainen et al. concluded that at present it is unknown how these historical trends could be mediated. The postwar secular decline of the male:female ratio at birth is not an isolated phenomenon and parallels the decline of perinatal morbidity and mortality, congenital anomalies, and various constitutional diseases. This parallelism indicates a common etiology and may be caused by reduction of conceptopathology, as a correlate to increasing socioeconomic development. An inverted dose response or the dose-response fallacy due to vanishing male conceptuses explains the low sex ratios before World War I and World War II in newborns from black parents and from the lowest socioeconomic classes

The perceived waning of biologics in severe asthma

BACKGROUND: Biologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown.OBJECTIVE: To explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration.METHODS: Severe asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files.RESULTS: 65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5-7.5) on a 0-10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p &lt; 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval.CONCLUSION: Two-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.</p

Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain comparable statistical power. In conclusion, andrological methods and epidemiological designs are available for the implementation of valid studies concerned with environmental impact on human testicular function. Occupational sperm studies should probably not be the first choice when the objective is initial screening of environmental impact on fertility but should be implemented when their is a need to corroborate or refuse earlier evidence that specific exposures have impact on testicular function

Seismic and geochemical evidence for large-scale mantle upwelling beneath the eastern Atlantic and western and central Europe

Seismic tomography and the isotope geochemistry of Cenozoic volcanic rocks suggest the existence of a large, sheet-like region of upwelling in the upper mantle which extends from the eastern Atlantic Ocean to central Europe and the western Mediterranean. A belt of extension and rifting in the latter two areas appears to lie above the intersection of the centre of the upwelling region with the base of the lithosphere. Lead, strontium and neodymium isotope data for all three regions converge on a restricted composition, inferred to be that of the upwelling mantle

The role of atopy in otitis media with effusion among primary school children: audiological investigation

Objective of this study is to value the role of atopy in otitis media with effusion (OME) in children attending primary school in Western Sicily focusing on the audiological characteristics among atopic and non atopic subjects suffering from OME. 310 children (5-6 years old) were screened by skin tests and divided into atopics (G1) and non atopics (G2). The samples were evaluated for OME by pneumatic otoscopy, tympanogram and acoustic reflex tests. The parameters considered were: documented persistent middle ear effusion by otoscopic examination for a minimum of 3 months; presence of B or C tympanogram; absence of ipsilateral acoustic reflex and a conductive hearing loss greater than 25 dB at any one of the frequencies from 250 Hz through 4 kHz. 56 children (18.06%) resulted atopics while 254 were non atopics. OME was identified in 24 atopic children and in 16 non atopic children for a total number of 40 children; the overall prevalence rate was 12.9% (42.85% for G1 and 6.30% for G2). OME was bilateral in 28 children (70%), with a significative difference between G1 (79.17%) and G2 (56.25%). The prevalence of B tympanogram was 70.59%, corresponding to 79.07% for G1 and 56% for G2. The mean air conduction pure tone was respectively 31.97 dB for G1 and 29.8 dB for G2. The prevalence value of OME in atopics children, also supported by the higher predominance of bilaterality, B tympanogram and hearing loss among this group, could suggest the important role of allergy in the pathogenesis of OME

Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial

Background Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80% of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. It has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow up period, or of too poor quality to give a definite answer. The aim of the OSTRICH trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. Methods/Design 380 participants (children aged 2-8 years) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms attributable to OME for at least 3 months and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for one week. Outcomes include audiometry, tympanometry and otoscopy assessments, symptoms, adverse effects, functional health status, quality of life, resource use and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. Discussion There is an important evidence gap regarding clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, non-surgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS

Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study

Purpose The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. Methods HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. Results After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. Conclusion HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.Radiation, Radionuclides and ReactorsApplied Science

Development of microspheres for biomedical applications: a review

An overview of microspheres manufactured for use in biomedical applications based on recent literature is presented in this review. Different types of glasses (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres (both natural and synthetic) in the form of porous , non-porous and hollow structures that are either already in use or are currently being investigated within the biomedical area are discussed. The advantages of using microspheres in applications such as drug delivery, bone tissue engineering and regeneration, absorption and desorption of substances, kinetic release of the loaded drug components are also presented. This review also reports on the preparation and characterisation methodologies used for the manufacture of these microspheres. Finally, a brief summary of the existing challenges associated with processing these microspheres which requires further research and development are presented