High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.

What is the most relevant standard of success in assisted reproduction?: The cumulated singleton/twin delivery rates per oocyte pick-up: the CUSIDERA and CUTWIDERA.

National and international registries are essential tools for establishing new standards and comparing success rates, but they do not take into account the total pregnancy/delivery rate per oocyte recovery. In Switzerland and Germany, because of legal constraints, a maximum of three two-pronuclear zygotes are allocated for transfer whereas all the supernumerary pronuclear zygotes are immediately cryopreserved, preventing selection of the transferred embryos. We report on a 10 years' experience (1993-2002) of our centre which performs transfers of unselected embryos and cryopreservation at the two-pronuclear zygote stage. As approximately 30% of all deliveries are from cryo cycles, it is essential to take into account the contribution of the cryo transfers, and we propose therefore to evaluate, as a measure of IVF performance, the cumulated delivery rate per oocyte pick-up. This delivery rate is broken down further into the cumulated singleton delivery rate (CUSIDERA) and the cumulated twin delivery rate (CUTWIDERA). The sum (S) of these two rates is a measure of efficacy while the ratio CUTWIDERA/S as a percentage is a measure of safety of IVF treatments. Using these new indexes, the average 10 year efficacy and safety of our IVF programme were 26 and 19%, respectively. Both CUSIDERA and CUTWIDERA can be calculated easily in any clinical situation and yield useful parameters for patient counselling and internal/external benchmarking purposes.

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P<0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count >5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

The predation cost of being a male: implications for sex-specific rates of ageing

Evolutionary theory predicts that the rate of extrinsic (i.e. age- and condition-independent) mortality should affect important life history traits such as the rate of ageing and maximum lifespan. Sex-specific differences in mortality rates due to predation may therefore result in the evolution of important differences in life history traits between males and females. However, quantifying the role of predators as a factor of extrinsic mortality is notoriously difficult in natural populations. We took advantage of the unusual prey caching behaviour of the barn owl Tyto alba and the tawny owl Strix aluco to estimate the sex ratio of their five most common preys. For all prey species, there was a significant bias in the sex ratio of remains found in nests of both these owls. A survey of literature revealed that sex-biased predation is a common phenomenon. These results demonstrate that predation, a chief source of extrinsic mortality, was strongly sex-biased. This may select for alternate life history strategies between males and females, and account for a male life span being frequently lower than female lifespan in many animal species.

Improving influenza vaccination rates in the elderly.

BACKGROUND: Vaccination coverage for influenza in the elderly remains low when the physician is the only person responsible for immunization. Integration of other health care workers may improve the coverage rate of at-risk groups. OBJECTIVES: To estimate vaccination coverage rate by using a strategy based on the systematic intervention of a health care professional proposing vaccination before the doctor's consultation, to evaluate the changes in coverage rates before and after introduction of this strategy, and to assess the feasibility of this intervention and the achieved coverage rate in family physician offices. STUDY DESIGN: Prospective study in a medical outpatient clinic and 5 family physician practices in Switzerland. POPULATION: Participants consisted of all patients 65 years or older attending a medical outpatient clinic during the vaccination period in 1999 (n = 401), patients 65 years or older regularly followed at a medical outpatient clinic in 1998 and 1999 (n = 195), and patients 65 years or older presenting to 5 family physician offices in 1999 (n = 598). OUTCOME MEASURED: Rates of vaccination coverage. RESULTS: Among all participants, vaccination coverage rates in 1999 were 85% at the medical outpatient clinic and 83% in family physician offices. Among participants regularly followed at the medical outpatient clinic, vaccination coverage increased from 48% in 1998 to 76% in 1999. Rates of refusal were 9% at the medical outpatient clinic and 14% in the family physician offices. CONCLUSIONS: The systematic intervention of a health care professional to suggest vaccination before the doctor's visit is an effective measure to achieve high coverage rate. Such a strategy also improves outpatient clinic or private practice efficiency by reducing pressures on physicians.

Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens.

PURPOSE: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. RESULTS: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). CONCLUSION: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

Vaccination against human papillomavirus in Switzerland: simulation of the impact on infection rates.

OBJECTIVES: Human papillomavirus (HPV) is a sexually transmitted infection of particular interest because of its high prevalence rate and strong causal association with cervical cancer. Two prophylactic vaccines have been developed and different countries have made or will soon make recommendations for the vaccination of girls. Even if there is a consensus to recommend a vaccination before the beginning of sexual activity, there are, however, large discrepancies between countries concerning the perceived usefulness of a catch-up procedure and of boosters. The main objective of this article is to simulate the impact on different vaccination policies upon the mid- and long-term HPV 16/18 age-specific infection rates. METHODS: We developed an epidemiological model based on the susceptible-infective-recovered approach using Swiss data. The mid- and long-term impact of different vaccination scenarios was then compared. RESULTS: The generalization of a catch-up procedure is always beneficial, whatever its extent. Moreover, pending on the length of the protection offered by the vaccine, boosters will also be very useful. CONCLUSIONS: To be really effective, a vaccination campaign against HPV infection should at least include a catch-up to early reach a drop in HPV 16/18 prevalence, and maybe boosters. Otherwise, the protection insured for women in their 20s could be lower than expected, resulting in higher risks to later develop cervical cancer.

Coronary arteriography rates in Switzerland: how do they vary?

Coronary heart disease is a leading cause of death for both sexes in developed countries. Controversy has arisen about the health benefits and risks of coronary surgery and, more recently of coronary angioplasty. As a clinical prerequisite to these interventions, coronary arteriography can be considered an indicator of invasive services offered to coronary heart disease patients. We collected data on characteristics of all patients subjected to coronary arteriography during 1984 in Switzerland. A total of 4921 coronary arteriographies were performed among 4359 patients; this corresponds to 77 procedures/100,000 residents and 68 patients/100,000 residents. Rates for men are 4.2 times women's rates, and the highest utilization rate for both sexes are observed in the group aged 40-64. Large variations characterize cantonal and regional coronary arteriography rates. Similarly, the distribution of centers practising this procedure is not uniform. These observations are placed in the context of the general practice of coronary angiography, changes expected in the face of by-pass surgery and angioplasty expansion, and coronary heart disease data.

Biogeochemical weathering in sedimentary chronosequences of the Rhône and Oberaar Glaciers (Swiss Alps): rates and mechanisms of biotite weathering

We analysed the composition of phyllosilicate minerals in sediments deposited by the Rhone and Oberaar glaciers (Swiss Alps), in order to identify processes and rates of biogeochemical weathering in relation to glacial erosion. The investigated sediments are part of chronosequences consisting of (A) suspended, "fresh" sediment in melt water; (B) terminal moraines from the Little Ice Age (LIA; approximately 1560-1850); and (C) tilts of the Younger Dryas interval (YD; approximately 11'500y BP). Secondary weathering products associated with the suspended sediment have not been observed: we therefore exclude intermittent subglacial storage and weathering of this material and assume that the suspended sediment is directly derived from mechanically abraded bedrock. This implies that biogeochemical weathering processes started once the glacially-derived sediment was deposited in the proglacial area. The combination of a developing vegetation cover, the generally high permeability allowing the percolation of precipitation, and the chemical reactivity related to the dominance of fine-grained material (<63 pm) drives the weathering process and the initial Umbrepts present in LIA profiles undergo podzolisation and lead to the formation of Humods observed in YD profiles. Systematic XRD analyses of these chronosequences show a progressive decrease in biotite contents and a concomitant increase in pedogenically formed vermiculite with increasing sediment age. Biotite contents decrease by 25-50% in the upper 30 cm of the moraines after 145-275 yr in the proglacial environment. Biotite weathering rates are calculated using the difference in the biotite content between unweathered and weathered glacial sediments within the investigated profiles. The reactive mineral surface area is estimated geometrically, both with regards to the total relative surface (WRT) as well as to the relative edge surface (WRE). WRT Biotite weathering rates are estimated as 10(-13)-10-(15) mol(biotite) m(biotite)(-2) s(-1). WRE Biotite weathering rates are on the order of 10(-13)-10(-14) mol(biotite) m(biotite)(-2) s(-1). Biotite weathering rates obtained by this study are in the order of one magnitude higher in comparison to other published field-based weathering rates. Using biotite as an indicator, we therefore suggest that glacially-derived material in the area of the Oberaar and Rhone glaciers is generally subjected to enhanced biogeochemical weathering, starting immediately after deposition in the proglacial zone and subsequently continuing for thousands of years after glacier retreat.

Low rates of X-Y recombination, not turnovers, account for homomorphic sex chromosomes in several diploid species of Palearctic green toads (Bufo viridis subgroup).

Contrasting with birds and mammals, most ectothermic vertebrates present homomorphic sex chromosomes, which might be due either to a high turnover rate or to occasional X-Y recombination. We tested these two hypotheses in a group of Palearctic green toads that diverged some 3.3 million years ago. Using sibship analyses of sex-linked markers, we show that all four species investigated share the same pair of sex chromosomes and a pattern of male heterogamety with drastically reduced X-Y recombination in males. Phylogenetic analyses of sex-linked sequences show that X and Y alleles cluster by species, not by gametolog. We conclude that X-Y homomorphy and fine-scale sequence similarity in these species do not stem from recent sex-chromosome turnovers, but from occasional X-Y recombination.

Real-life versus package insert: a post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellers.

There are various methods to collect adverse events (AEs) in clinical trials. The methods how AEs are collected in vaccine trials is of special interest: solicited reporting can lead to over-reporting events that have little or no biological relationship to the vaccine. We assessed the rate of AEs listed in the package insert for the virosomal hepatitis A vaccine Epaxal(®), comparing data collected by solicited or unsolicited self-reporting. In an open, multi-centre post-marketing study, 2675 healthy travellers received single doses of vaccine administered intramuscularly. AEs were recorded based on solicited and unsolicited questioning during a four-day period after vaccination. A total of 2541 questionnaires could be evaluated (95.0% return rate). Solicited self-reporting resulted in significantly higher (p<0.0001) rates of subjects with AEs than unsolicited reporting, both at baseline (18.9% solicited versus 2.1% unsolicited systemic AEs) and following immunization (29.6% versus 19.3% local AEs; 33.8% versus 18.2% systemic AEs). This could indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert. The distribution of AEs differed significantly between the applied methods of collecting AEs. The most common AEs listed in the package insert were reported almost exclusively with solicited questioning. The reporting of local AEs was more likely than that of systemic AEs to be influenced by subjects' sex, age and study centre. Women reported higher rates of AEs than men. The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed.

Can we continue to neglect genomic variation in introgression rates when inferring the history of speciation? A case study in a Mytilus hybrid zone.

The use of molecular data to reconstruct the history of divergence and gene flow between populations of closely related taxa represents a challenging problem. It has been proposed that the long-standing debate about the geography of speciation can be resolved by comparing the likelihoods of a model of isolation with migration and a model of secondary contact. However, data are commonly only fit to a model of isolation with migration and rarely tested against the secondary contact alternative. Furthermore, most demographic inference methods have neglected variation in introgression rates and assume that the gene flow parameter (Nm) is similar among loci. Here, we show that neglecting this source of variation can give misleading results. We analysed DNA sequences sampled from populations of the marine mussels, Mytilus edulis and M. galloprovincialis, across a well-studied mosaic hybrid zone in Europe and evaluated various scenarios of speciation, with or without variation in introgression rates, using an Approximate Bayesian Computation (ABC) approach. Models with heterogeneous gene flow across loci always outperformed models assuming equal migration rates irrespective of the history of gene flow being considered. By incorporating this heterogeneity, the best-supported scenario was a long period of allopatric isolation during the first three-quarters of the time since divergence followed by secondary contact and introgression during the last quarter. By contrast, constraining migration to be homogeneous failed to discriminate among any of the different models of gene flow tested. Our simulations thus provide statistical support for the secondary contact scenario in the European Mytilus hybrid zone that the standard coalescent approach failed to confirm. Our results demonstrate that genomic variation in introgression rates can have profound impacts on the biological conclusions drawn from inference methods and needs to be incorporated in future studies.

Rates and pattern of evolution among Cretaceous radiolarians: relations with global paleoceanographic events

We present a new approach for analyzing the turnover rates of Cretaceous radiolarians recorded in pelagic sequences of western Tethys, The analysis of major extinction-radiation events and the fluctuation of diversity are compared with major paleoceanographic events and variation of diversity in dinoflagellates, calcareous nannoplankton and ammonites. There is an extraordinary correlation between biotic changes and sea level changes, temperatures, O, C and Sr isotopes, phosphorus accumulation rates and anoxic episodes. This reveals a predominantly abiotic control on the evolution of radiolarians. The rate of turnover and the diversity through time of two major orders of radiolarians (nassellarians and spumellarians) exhibits (1) the quasi-parallelism of their diversity curves, excluding a direct competition between them, (2) greater resistance of spumellarians to extinction during the early stage of extinction intervals and (3) a stronger post-extinction recovery of nassellarians. Evolutionary rates of radiolarians can be a good means of monitoring global environmental changes and allowing us to understand more clearly the relationship between plankton evolution, climate and pale oceanographic processes.