Identifying the parent-of-origin of de novo SNVs in schizophrenia

Several studies over the last few years have shown that newly arising (de novo) mutations contribute to the genetics of schizophrenia (SZ), autism (ASD) and other developmental disorders. The strongest evidence comes from studies of de novo Copy Number Variation (CNV), where the rate of new mutations is shown to be increased in cases when compared to controls [23, 24]. Research on de novo point mutations and small insertion-deletions (indels) has been more limited, but with the development of next-generation sequencing (NGS) technology, such studies are beginning to provide preliminary evidence that de novo single-nucleotide mutations (SNVs) might also increase risk of SZ and ASD [25, 26] Advanced paternal age is a major source of new mutations in human beings [27] and could thus be associated with increased risk for developing SZ, ASD or other developmental disorders. Indeed, advanced paternal age is found to be a risk factor for developing SZ and ASD in the offspring [28, 29] and new mutations related to advanced paternal age have been implicated as a cause of sporadic cases in several autosomal dominant diseases, some neurodevelopmental diseases, including SZ and ASD, and social functioning. New single-base substitutions occur at higher rates at males compared to females and this difference increases with paternal age. This is due to the fact that sperm cells go through a much higher number of cell divisions (~840 by the age of 50), which increases the risk for DNA copy errors in the male germ line [30] . By contrast, the female eggs (oocytes) undergo only 24 cell divisions and all but the last occur during foetal life. The aim of my project is to determine the parent-of-origin of de novo SNVs, using large samples of parent-offspring trios affected with schizophrenia (SZ). From whole exome sequencing of 618 Bulgarian proband-offspring trios affected, nearly 1000 de novo (SNVs or small indels) have been identified and from these, the parent-of-origin of at least 60% of the mutations (N=600) can be established. This project is contained in a main one that consists on the determination of the parental origin of different types of de novo mutations (SNVs, small indels and large CNVs).

A comparison of the dental status and treatment needs of older adults with and without chronic mental illness in Sevilla, Spain

Objectives: To study the dental status and treatment needs of institutionalized older adults with chronic mental illness compared to a non-psychiatric control sample. Study Design: The sample size was 100, in which 50 were psychogeriatric patients (study group; SG) classified according to DSM-IV, with a mean age of 69.6 ± 6.7 years, and 50 non-psychiatric patients (control group; CG), with a mean age of 68.3 ± 6.9 years. Clinical oral health examinations were conducted and caries were recorded clinically using the Decayed, Missing and Filled Teeth Index (DMFT). Results were analyzed statistically using the Student"s t-test or analysis of variance. Results: Caries prevalence was 58% and 62% in SG and CG, respectively. DMFT index was 28.3 ± 6.6 in SG and 21.4 ± 6.07 in CG (p < 0.01). Mean number of decayed teeth was higher in SG (3.1) compared to CG (1.8) (p=0.047). Mean number of missing teeth were 25.2 and 16.4 in SG and CG respectively (p<0.05). DMFT scores were higher in SG in all the age groups (p < 0.01). Mean number of teeth per person needing treatment was 3.4 in SG and 1.9 in CG (p= 0.037). The need for restorative dental care was significantly lower in the SG (0.8 teeth per person) than in the CG (1.7 teeth per person) (p = 0.043). Conclusions: Institutionalized psychiatric patients have significantly worse dental status and more dental treatment needs than non-psychiatric patients.

Variability of the radius growth at 25 years old Pinus uncinata Miller ex Mirbel in the North-East Spanish Pyrenees

It has been studied the variability of stem radial growth in four radius orientations at the age of 25 years old trees. The species was Pinus uncinata. The sampling sites, located in the North East Spanish Pyrenees belong to different plant communities. An ANOVA analysis was performed in order to find out which factors, the radio orientation, plant community of the site and tree itself are significative or have some kind of influence on the tree radial growth.

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

Background: During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia.

The prevalence of child sexual abuse in community and student samples: A meta-analysis

Background: Studies conducted internationally confirm that child sexual abuse is a much more widespread problem than previously thought, with even the lowest prevalence rates including a large number of victims that need to be taken into account. Objective: To carry out a meta-analysis of the prevalence of child sexual abuse in order to establish an overall international figure. Methods: Studies were retrieved from various electronic databases. The measure of interest was the prevalence of abuse reported in each article, these values being combined via a random effects model. A detailed analysis was conducted of the effects of various moderator variables. Results: Sixty-five articles covering 22 countries were included. The analysis showed that 7.9% of men (7.4% without outliers) and 19.7% of women (19.2% without outliers) had suffered some form of sexual abuse prior to the age of eighteen. Conclusions: The results of the present meta-analysis indicate that child sexual abuse is a serious problem in the countries analysed.

Benign fibro-osseous lesions of the maxillas: analysis of 11 cases

Introduction: A study is made of the principal characteristics of the oral lesions biopsied in our Service of Oral Surgery and histologically diagnosed as corresponding to fibro-osseous lesions of the maxillas. Patients and methods: A retrospective review was made of all the biopsies made in a Service of Oral Surgery between 1996 and 2003. The reason for consultation was analyzed, along with patient age, sex, clinical and radiological characteristics, tentative diagnosis, histological diagnosis and treatment provided. Results: A total of 1238 biopsies were performed during the study period. Of these, only 11 corresponded to benign fibro-osseous lesions (7 women and 4 men). The mean patient age was 44 years (range 19-72 years). The most frequent location was the mandible (8 of the cases). In 7 patients the lesions constituted casual radiological findings; 4 presented bulging of the vestibular cortical bone, though only one of them reported pain. The histological diagnoses comprised 7 cemento-ossifying fibromas and 4 fibrous dysplasias. In 9 cases surgical resection was carried out, while in one case an incisional biopsy was performed, and in the remaining case curettage was decided. Discussion: These lesions are more frequent in women than in men, and the age at presentation is variable. In terms of lesion location, fibrous dysplasia is more common in the upper maxilla, while cemento-ossifying fibroma is more frequently found in the mandible. The diagnosis of such lesions is established upon contrasting the data obtained from the anamnesis, physical examination, the radiological characteristics, the intraoperative findings and the histological study, since both disorders have similar clinical and histological features- despite the fact that they constitute distinct disease conditions.

Approach to the Lower Pliocene marine-continental correlation from southern Spain. The micrommamal site of Alhaurín el Grande-1 (Málaga Basin, Betic Cordillera, Spain)

A new micromammal site at Alhaurín el Grande (Málaga, southern Spain) located above early Pliocene marine deposits allows an approach to the marine-continental correlation for this age. The early Pliocene marine filling throughout the Málaga Basin is developed in three transgressive-regressive sequences (Pl-1, Pl-2, and Pl-3 units) bounded by discontinuities. At the top of the intermediate sequence Pl-2, peaty sediments have yielded fossils of Rodentia, Lagomorpha, Insectivora, and Crocodylia. The presence of Cricetus barrieri Mein & Michaux, 1970 in combination with murids, both of primitive morphology, such as Apodemus gudrunae Van de Weerd, 1976, and more advanced forms (i.e. Occitanomys brailloni Michaux, 1969 and Stephanomys donnezani cordii Ruiz Bustos, 1986), points to an early Ruscinian age (MN 14 biozone). Based on the planktonic foraminifers, the biostratigraphic data indicate that marine sediments just below the micromammal beds belong to the MPl-2 biozone of the early Zanclean. Available paleomagnetic data from the marine sediments show that the micromammal bed must be located between the normal geomagnetic subchron C3n3n (4.89-4.80 Ma) and the subchron C3n2n (4.63-4.49 Ma), limiting the age of this site to the late part of the early Zanclean.

Prevalence of smoking among dentists in Catalonia - Spain (2006). Literature review of smoking cessation practices in the dental office

Objective: The objective of this study was to collect data on the prevalence of smokers among Catalonian dentists (by age and sex) and compare them with existing data on the general population, doctors, registered nurses and pharmacists. The overall prevalence of smokers in Catalonia (2006) was 34.5% of men and 24.3% of women. Data available on the prevalence of smoking among doctors (26.3% men and 22.1% women), pharmacists (19.8% men and 20.6% women) and registered nurses (34.1% men and 35.3% women) relates to the year 2002. Study design: In September 2006, Catalonian dentists (n=3,799) were asked about their habits in relation to tobacco in a self-administered questionnaire, on use and opinions with respect to dental amalgam. Five hundred and seventynine questionnaires were received, of which 538 answered the question on smoking (14.2% of the sample universe). Results: The prevalence of smokers among dentists is lower (24.9% of men and 18.4% of women) than in the general population and other healthcare professionals. In dentists in the age group between 25 and 34 years, the prevalence was 26.1% in men and 14.9% in women, while the prevalence in this age group in the general population was 43.6% and 37.1%, respectively. Conclusion: Catalonian dentists have a much lower prevalence of tobacco use than the general population and lower even than other healthcare professionals. Given that non-smoking healthcare professionals have better awareness for providing recommendations for smoking prevention and cessation, Catalonian dentists may be a valid group for performing this task for which there is scientific evidence.

Labor Mobility of the Chinese Graduates from British and Spanish Universities: What Happens to the "Talent Migration"?

The scholarship on migration in Europe heavily focuses on the integration of economically vulnerable migrants. In the age of commercialization of education, however, the European Union attracts a rising number of highly skilled non-EU migrants that take up studies across the continent. Despite economic downturn, the EU universities experience a rapid growth in the number of Chinese students, many of whom settle in Europe upon graduation. Surprisingly, although the number of Chinese students in the EU increases, scholars largely ignore the labor paths that these highly skilled migrants take upon graduating from European universities. This study aims to fill this gap by exploring the variation in the Chinese graduates’ labor incorporation patterns and in their spatial mobility. In this project, I also examine macro-level hypotheses predicting that the EU and host states’ labor market institutions, changes in the EU policies on the highly skilled and the outburst of economic crisis matter for the Chinese highly skilled social and spatial mobility. Seizing on surveys, interviews and on the bodies of literature on stratification and social mobility, economic incorporation, social capital and human capital, I look at the Chinese students that graduated from universities in Great Britain and Spain. These states differ in the university tuition fees, migration policies towards the highly skilled workers and in the period of the Chinese students’ influx, thus providing an economically and socially diverse sample. My research will contribute to the literature on the relations between migrants’ social mobility, class and status background and spatial mobility, at the same time adding a transnational level perspective to the study of highly skilled Asian migration.

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

The European Cancer Registry-based project on hematologic malignancies (HAEMACARE), setup to improve the availability and standardization of data on hematologic malignancies in Europe, used the European Cancer Registry-based project on survival and care of cancer patients (EUROCARE-4) database to produce a new grouping of hematologic neoplasma(defined by the International Classification of Diseases for Oncology, Third Edition and the 2001/2008 World Health Organization classifications) for epidemiological and public healthpurposes. We analyzed survival for lymphoid neoplasms in Europe by disease group, comparing survival between different European regions by age and sex. Design and Methods Incident neoplasms recorded between 1995 to 2002 in 48 population-based cancer registries in 20 countries participating in EUROCARE-4 were analyzed. The period approach was used to estimate 5-year relative survival rates for patients diagnosed in 2000-2002, who did not have 5years of follow up. Results: The 5-year relative survival rate was 57% overall but varied markedly between the definedgroups. Variation in survival within the groups was relatively limited across European regions and less than in previous years. Survival differences between men and women were small. The relative survival for patients with all lymphoid neoplasms decreased substantially after the age of 50. The proportion of ‘not otherwise specified’ diagnoses increased with advancing age.Conclusions: This is the first study to analyze survival of patients with lymphoid neoplasms, divided into groups characterized by similar epidemiological and clinical characteristics, providing a benchmarkfor more detailed analyses. This Europe-wide study suggests that previously noted differences in survival between regions have tended to decrease. The survival of patients with all neoplasms decreased markedly with age, while the proportion of ‘not otherwise specified’ diagnoses increased with advancing age. Thus the quality of diagnostic work-up and care decreased with age, suggesting that older patients may not be receiving optimal treatment

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia

Systemic lupus erythematosus in the elderly: Clinical and immunological characteristics.

Systemic lupus erythematosus (SLE) predominantly affects young women in their 20s. In 40 out of 250 (16%) patients with SLE seen in our hospital disease onset occurred after the age of 50. The interval between the time of onset and diagnosis was five years in this older group compared with three years in the younger group. Arthritis, as a first symptom, was less common in the older onset group. During the follow up a lower incidence of arthritis, malar rash, photosensitivity, and nephropathy was found in the older onset group. In contrast, this group showed an increased incidence of myositis. High titres of anti-dsDNA tended to occur less often and the incidence of anti-Ro antibodies was lower in the older onset group. These features seem to distinguish patients with older onset SLE as a particular subset.