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1.
BJOG ; 128(13): 2073-2082, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34455684

RESUMEN

OBJECTIVE: To investigate whether polycystic ovary syndrome (PCOS) is associated with increased risk of stillbirth and whether any such association is linked to PCOS with a severe hyperandrogenic profile. DESIGN: Nationwide register-based cohort study. SETTING: Sweden. POPULATION: The cohort consisted of women giving birth to singleton infants in 1997-2015. All women with a diagnosis of PCOS in the period 1997-2017 and a randomly selected reference group of women without PCOS diagnosis were included. PCOS with a severe hyperandrogenic profile was defined as a PCOS diagnosis with at least two dispensations of prescribed anti-androgens during 2005-2017. METHODS: The risk of stillbirth in women with PCOS was estimated through multiple logistic regression, using women without PCOS as a reference. Risks were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity, body mass index, type-1 diabetes, educational level and country of birth. MAIN OUTCOME MEASURES: Stillbirth, at ≥22 weeks of gestation in 2008-2015 and at ≥28 weeks of gestation in 1997-2007. RESULTS: Compared with women without PCOS (n = 241 750), women with PCOS (n = 41 851) had a 50% increased risk of stillbirth (aOR 1.50, 95% CI 1.28-1.77). The incidence of stillbirth in women with PCOS was particularly increased at term. Women with PCOS and a severe hyperandrogenic profile (n = 13 713) did not have a stronger association with stillbirth than women with PCOS who did not have such a profile. CONCLUSIONS: PCOS is associated with stillbirth and should be considered as a possible risk factor in antenatal care. Further research is warranted to investigate possible causal mechanisms. TWEETABLE ABSTRACT: Women with PCOS have increased risk of stillbirth, and the incidence is particularly increased at term.


Asunto(s)
Síndrome del Ovario Poliquístico/complicaciones , Mortinato/epidemiología , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Incidencia , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Edad Materna , Paridad , Síndrome del Ovario Poliquístico/epidemiología , Embarazo , Sistema de Registros , Factores de Riesgo , Suecia/epidemiología
2.
BMC Ecol ; 17(1): 15, 2017 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-28399832

RESUMEN

BACKGROUND: Invasions pose a large threat to native species, but the question of why some species are more invasive, and some communities more prone to invasions than others, is far from solved. Using 10 different three-species bacterial communities, we tested experimentally if the phylogenetic relationships between an invader and a resident community and the propagule pressure affect invasion probability. RESULTS: We found that greater diversity in phylogenetic distances between the members of resident community and the invader lowered invasion success, and higher propagule pressure increased invasion success whereas phylogenetic distance had no clear effect. In the later stages of invasion, phylogenetic diversity had no effect on invasion success but community identity played a stronger role. CONCLUSIONS: Taken together, our results emphasize that invasion success does not depend only on propagule pressure, but also on the properties of the community members. Our results thus indicate that invasion is a process where both invader and residing community characters act in concert.


Asunto(s)
Bacterias/genética , Variación Genética , Filogenia , Serratia marcescens/fisiología , Animales , Bacterias/clasificación , Fenómenos Fisiológicos Bacterianos , Serratia marcescens/clasificación , Serratia marcescens/genética
3.
Evolution ; 70(11): 2562-2572, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27624666

RESUMEN

To predict evolutionary responses of warning signals under selection, we need to determine the inheritance pattern of the signals, and how they are genetically correlated with other traits contributing to fitness. Furthermore, protective coloration often undergoes remarkable changes within an individual's lifecycle, requiring us to quantify the genetic constraints of adaptive coloration across all the relevant life stages. Based on a 12 generation pedigree with > 11,000 individuals of the wood tiger moth (Arctia plantaginis), we show that high primary defense as a larva (large warning signal) results in weaker defenses as adult (less efficient warning color), due to the negative genetic correlation between the efficacy of larval and adult warning coloration. However, production of effective warning coloration as a larva did not incur any life-history costs and was positively genetically correlated with reproductive output. These results provide novel insights into the evolutionary constraints on protective coloration in animals, and explain the maintenance of variation in the signal expression despite the strong directional selection by predators. By analyzing the genetic and environmental effects on warning signal and life-history traits in all relevant life stages, we can accurately determine the mechanisms shaping the evolutionary responses of phenotypic traits under different selection environments.


Asunto(s)
Adaptación Fisiológica/genética , Evolución Molecular , Variación Genética , Mariposas Nocturnas/genética , Pigmentación/genética , Animales , Larva/genética , Mariposas Nocturnas/anatomía & histología , Mariposas Nocturnas/crecimiento & desarrollo , Selección Genética
4.
Br J Surg ; 103(7): 908-15, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27115862

RESUMEN

BACKGROUND: The development of colorectal cancer is influenced by hormonal factors. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. The aim of this cohort study was to examine colorectal cancer risk after oophorectomy for benign indications. METHODS: Women who had undergone oophorectomy between 1965 and 2011 were identified from the Swedish Patient Registry. Standard incidence ratios (SIRs) and 95 per cent confidence intervals for colorectal cancer risk were calculated compared with those in the general population. Stratification was carried out for unilateral and bilateral oophorectomy, and hysterectomy without specification of whether the ovaries were removed or not. Associations between the three oophorectomy options and colorectal cancer risk in different locations were assessed by means of hazard ratios (HRs) and 95 per cent confidence intervals calculated by Cox proportional hazards regression modelling. RESULTS: Of 195 973 women who had undergone oophorectomy, 3150 (1·6 per cent) were diagnosed with colorectal cancer at a later date (median follow-up 18 years). Colorectal cancer risk was increased after oophorectomy compared with that in the general population (SIR 1·30, 95 per cent c.i. 1·26 to 1·35). The risk was lower for younger age at oophorectomy (15-39 years: SIR 1·10, 0·97 to 1·23; 40-49 years: SIR 1·26, 1·19 to 1·33; P for trend < 0·001). The risk was highest 1-4 years after oophorectomy (SIR 1·66, 1·51 to 1·81; P < 0·001). In the multivariable analysis, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had only unilateral oophorectomy (HR 2·28, 95 per cent c.i. 1·33 to 3·91). CONCLUSION: Colorectal cancer risk is increased after oophorectomy for benign indications.


Asunto(s)
Neoplasias Colorrectales/epidemiología , Ovariectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Sistema de Registros , Medición de Riesgo , Suecia/epidemiología , Adulto Joven
6.
Parasitology ; 142(8): 1108-14, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25899555

RESUMEN

A study was carried out to investigate how common Cryptosporidium infections are in beef calves in Swedish suckler herds and to explore which species and subtypes that occur. We further aimed at identifying factors associated with shedding of Cryptosporidium oocysts in this type of calf management. The study was conducted in two regions in Sweden and included 30 herds. Faecal samples were collected from calves younger than 3 months. A brief clinical examination was done and a questionnaire was used to collect data on management routines. Faeces were cleaned and concentrated and oocysts identified by epifuorescence microscopy. Cryptosporidium positive samples were analyzed at the 18S rRNA and GP60 genes to determine species and Cryptosporidium parvum subtype, respectively. Logistic regression was used to identify factors associated with infection. Oocysts were detected in 122 (36.7%) calves from 29 (97%) herds, at 400 to 2.4 × 107 OPG. The youngest positive calves were only 1 and 2 days old. There was no association between age and Cryptosporidium infection. Cryptosporidium bovis, Cryptosporidium ryanae, C. parvum and Cryptosporidium ubiquitum were identified, with C. bovis being the major species. Two C. parvum subtypes, IIaA16G1R1 and IIdA27G1 were identified. Routines for cleaning calf pens and number of cows in calving pens were associated with infection.


Asunto(s)
Enfermedades de los Bovinos/epidemiología , Criptosporidiosis/epidemiología , Animales , Animales Recién Nacidos , Bovinos , Enfermedades de los Bovinos/parasitología , Criptosporidiosis/parasitología , Cryptosporidium/genética , Heces/parasitología , Femenino , Masculino , Oocistos , Prevalencia , ARN Ribosómico/genética , Especificidad de la Especie , Suecia/epidemiología
7.
Ann Oncol ; 26(1): 81-88, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25361981

RESUMEN

BACKGROUND: We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. PATIENTS AND METHODS: The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and ß-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. RESULTS: A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and ß-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. CONCLUSIONS: We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information. CLINICALTRIALS.GOV: This is the translational part of the Swedish multicenter and randomized trial TEX, clinicaltrials.gov identifier nct01433614 (http://www.clinicaltrials.gov/ct2/show/nct01433614).


Asunto(s)
Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Recurrencia Local de Neoplasia/genética , Apoptosis/genética , Mama/patología , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Caspasa 3/genética , Supervivencia sin Enfermedad , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Recurrencia Local de Neoplasia/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proteínas ras/genética
8.
Ann Oncol ; 26(3): 517-22, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25488685

RESUMEN

BACKGROUND: Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. PATIENTS AND METHODS: A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. RESULTS: PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83-0.99], P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82-0.98), P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76-1.00), P = 0.058] with no evidence of heterogeneity. When enriched for 'true' interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62-0.89), P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017). CONCLUSION: To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Detección Precoz del Cáncer/métodos , Predisposición Genética a la Enfermedad/genética , Mamografía/métodos , Transcriptoma/genética , Adulto , Anciano , Densidad de la Mama , Neoplasias de la Mama/epidemiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Glándulas Mamarias Humanas/anomalías , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Sistema de Registros , Suecia/epidemiología
9.
Plant Biol (Stuttg) ; 17(2): 351-60, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25272333

RESUMEN

The pericarp anatomy and the effects of storage after harvest, storage temperature and early cypsela imbibition on phytohormone profiles were studied in inbred sunflower lines B123 and B91. On day 0, germination of B123 cypselas was near 0%, indicating dormancy, whereas that of B91 cypselas was near 100%, indicating non-dormancy. The germination of B123 and B91 on day 33 at room temperature (25 °C) storage was similar. Cell wall thickness and sclerification of the pericarp were higher in B123 than B91, suggesting that structural characteristics may contribute to physical dormancy in B123. Jasmonates (JAs), salicylic acid (SA) and abscisic acid (ABA) were measured in dry and imbibed pericarps. SA content of dry pericarp was higher on day 33 than day 0. SA content during imbibition on day 33 was similar for room and low (-20 °C) storage temperatures. ABA content after 12 h imbibition was similar on days 0 and 33 at low temperature, but it increased on day 33 at room temperature for B123. 12-Oxo-phytodienoic acid (OPDA) was maximal on day 0 for B123, but peaked at day 33 at low temperature for B91. JA was higher on days 0 and 33 at room temperature as compared with low temperature. Our findings indicate that pericarp hormone profiles are affected in the two lines with different dormancy degree depending on storage conditions and imbibition processes.


Asunto(s)
Helianthus/anatomía & histología , Helianthus/fisiología , Reguladores del Crecimiento de las Plantas/metabolismo , Ácido Abscísico/análisis , Ácido Abscísico/metabolismo , Pared Celular/química , Ciclopentanos/análisis , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Ácidos Grasos Insaturados/análisis , Ácidos Grasos Insaturados/metabolismo , Germinación/efectos de los fármacos , Helianthus/efectos de los fármacos , Helianthus/genética , Oxilipinas/análisis , Oxilipinas/metabolismo , Oxilipinas/farmacología , Latencia en las Plantas , Reguladores del Crecimiento de las Plantas/análisis , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacología , Semillas/anatomía & histología , Temperatura
10.
Ann Oncol ; 25(10): 1966-1972, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25057175

RESUMEN

BACKGROUND: Breast cancer survival has been shown to be associated among relatives. In this study, we used a population-based cohort of Swedish sisters, both diagnosed with breast cancer, to determine whether prognostic information of a previously diagnosed sibling is useful for the clinical management of a newly diagnosed sibling. PATIENTS AND METHODS: The population-based cohort included all sister pairs, 1617 sisters, diagnosed with breast cancer in Sweden, from 1 January 1992, through 31 December 2006, with complete follow-up. All information was collected manually from original pathology reports and patient records. The Kappa statistic was used to measure the agreement of primary tumor characteristics between the sisters. We modeled the breast cancer-specific survival using multivariate (Cox) proportional hazard analyses in two steps categorizing the older sister's survival. RESULTS: Estrogen receptor status was the only tumor characteristic significantly associated between the sisters [κ 0.18 (95% confidence interval (CI) 0.089-0.27)]. Younger sisters with poor older sister survival showed significantly worse survival compared with patients with good older sister survival (log rank, P = 0.017). A twofold increased hazard ratio (HR) for death from breast cancer was found in younger sisters with poor older sister survival compared with patients with good sister survival [HR 2.56 (95% CI 1.16-5.65)], adjusting for age and calendar period of diagnosis, socioeconomic factors, number of children and hospital of primary tumor diagnosis. When further adjusting for primary tumor characteristics and adjuvant therapy, the risk for death from breast cancer in younger sisters with poor older sister survival became more pronounced [HR 3.35 (1.34-8.34)]. CONCLUSIONS: Our findings derived from a population-based cohort of Swedish sister pairs suggest that breast cancer-specific survival is inherited independent of tumor characteristics and treatment in the sibling later diagnosed with the disease. Prognostic information of a previously diagnosed sibling with breast cancer could be important in the clinical management.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Pronóstico , Hermanos , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Suecia , Población Blanca
11.
Insect Mol Biol ; 23(5): 566-78, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24924142

RESUMEN

Behavioural and physiological changes during diapause, an important strategy of insects for surviving harsh seasonal conditions, have been intensively studied. The genetic and molecular mechanisms underpinning diapause development are less well known. We took a candidate gene approach to study prediapause gene expression patterns in the Colorado potato beetle (Leptinotarsa decemlineata), an invasive insect that has rapidly spread northwards to high seasonality environments. Newly eclosed beetles originating from southern (Italy) and northern (Russia) Europe were reared under short- [12 h light (L):12 h dark (D)] and long-day (18L:6D) photoperiods for 10 days. This time period includes the sensitive period for the photoperiodic induction and initiation of diapause. Gene expression trajectories of 12 diapause-related genes (regulatory, metabolic and stress-resistance) were analysed from 0-, 5- and 10-day-old beetles. Gene expression differences increased with age, deviating significantly between populations and photoperiods in 10-day-old beetles. The gene expression profiles, particularly those related to energy metabolism and stress-resistance, indicate that beetles originating from Russia also prepare for diapause under the long-day photoperiod and show qualitative differences in the diapausing phenotype. Our study shows that population-dependent differences seen in behavioural and physiological traits connected with diapause in L. decemlineata are also evident in the expression trajectories of diapause-related genes.


Asunto(s)
Escarabajos/fisiología , Diapausa de Insecto , Regulación del Desarrollo de la Expresión Génica , Proteínas de Insectos/genética , Transcriptoma , Animales , Escarabajos/genética , Femenino , Proteínas de Insectos/metabolismo , Fotoperiodo , Reacción en Cadena en Tiempo Real de la Polimerasa
12.
Ann Oncol ; 23 Suppl 10: x349-53, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22987990

RESUMEN

Today, the diagnosis of metastatic breast cancer is usually based on radiological findings, and therapeutic decisions are made by considering the pathological characteristics and predictive markers of the primary tumour. Accumulating evidence suggests that tumour characteristics, including estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), are unstable through tumour progression. Several retrospective studies and, recently, two prospective studies have investigated the discrepancies in receptor status between primary tumours and the corresponding metastases in a total of 1773 patients (for ER) and 2845 patients (for HER2). Changes in ER and HER2 status in these studies range from 14.5% to 40% and from 0% to 37.5%, respectively. In the two prospective studies, a different diagnosis, usually non-malignant, was obtained in 3% and 9% of the cases, and the biopsy led to a treatment modification in about one out of seven patients. Here, we review and discuss the currently available data and provide our recommendations on when a metastatic biopsy should be obtained.


Asunto(s)
Neoplasias de la Mama , Recurrencia Local de Neoplasia , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Biomarcadores de Tumor/metabolismo , Biopsia , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Estudios Prospectivos , Receptores de Progesterona/metabolismo , Recurrencia , Estudios Retrospectivos
13.
Aliment Pharmacol Ther ; 35(4): 451-7, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22221173

RESUMEN

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking. AIM: To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD. METHODS: From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia. RESULTS: The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo- (n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. CONCLUSIONS: Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.


Asunto(s)
Colagogos y Coleréticos/administración & dosificación , Colangitis Esclerosante/tratamiento farmacológico , Neoplasias Colorrectales/prevención & control , Ácido Ursodesoxicólico/administración & dosificación , Adolescente , Adulto , Anciano , Colangitis Esclerosante/complicaciones , Estudios de Cohortes , Neoplasias Colorrectales/etiología , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Suecia , Adulto Joven
14.
Clin Pharmacol Ther ; 89(4): 503-12, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21326288

RESUMEN

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.


Asunto(s)
Guías como Asunto , Cooperación Internacional , Legislación de Medicamentos , Congresos como Asunto , Aprobación de Drogas , Europa (Continente) , Humanos , Japón , Estados Unidos
15.
J Evol Biol ; 20(2): 780-91, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17305843

RESUMEN

Inexperienced predators are assumed to select for similarity of warning signals in aposematic species (Müllerian mimicry) when learning to avoid them. Recent theoretical work predicts that if co-mimic species have unequal defences, predators attack them according to their average unpalatability and mimicry may not be beneficial for the better defended co-mimic. In this study, we tested in a laboratory environment whether a uniform warning signal is superior to a variable one in promoting predator learning, and simultaneously whether co-mimics are preyed upon according to their average unpalatability. There was an interaction of signal variation and unpalatability but inexperienced birds did not select for signal similarity in artificial prey; when the prey was moderately defended a variable signal was even learnt faster than a uniform one. Due to slow avoidance learning, moderately defended prey had higher mortality than highly defended prey (although this was not straightforward), but mixing high and moderate unpalatability did not increase predation compared with high unpalatability. This does not support the view that predators are sensitive to varying unpalatability. The results suggest that inexperienced predators may neither strongly select for accurate Müllerian mimicry nor affect the benefits of mimicry when the co-mimics are unequally defended.


Asunto(s)
Aprendizaje , Passeriformes/fisiología , Conducta Predatoria/fisiología , Adaptación Fisiológica , Animales , Evolución Biológica , Memoria
16.
J Evol Biol ; 19(2): 649-56, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16599939

RESUMEN

Predation is considered as an important factor constraining the expression of sexual signals. Nevertheless, direct quantitative evidence for predation provoking significant viability costs on individuals signalling at high rates is scarce. Moreover, it is unclear whether high rate signallers are able to balance presumably increased predation costs. We examined whether a condition dependent audible sexual signal, drumming, makes Hygrolycosa rubrofasciata male spiders more prone to predation by pied flycatchers (Ficedula hypoleuca), and whether sexual signalling rate is related to escaping ability once attacked. When birds were given a choice between two spider males manipulated to drum either one or three bouts per minute using playbacks, naïve birds attacked the males randomly regardless of the drumming rate. However, experienced birds chose significantly more often the males with high signalling rate. When spiders were allowed to escape, males with high sexual signalling rate tended to be better at escaping attacks than males with low sexual signalling rate. This study provides evidence that high signalling rate increases the risk of predation, but simultaneously males with high mobility, which correlates positively with signalling rate seemed to be better at compensating this cost.


Asunto(s)
Conducta Predatoria/fisiología , Conducta Sexual Animal/fisiología , Pájaros Cantores/fisiología , Animales , Reacción de Fuga , Femenino , Masculino , Transducción de Señal , Arañas
17.
Stat Med ; 25(18): 3110-23, 2006 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-16372390

RESUMEN

Estimation of genetic and environmental contributions to cancers falls in the framework of generalized linear mixed modelling with several random effect components. Computational challenges remain, however, in dealing with binary or survival phenotypes. In this paper, we consider the analysis of melanoma onset in a population of 2.6 million nuclear families in Sweden, for which none of the current survival-based methodologies is feasible. We treat the disease outcome as a binary phenotype, so that the standard proportional hazard model leads to a generalized linear model with the complementary-log link function. For rare diseases this link is very close to the probit link, and thus allows the use of marginal likelihood for the estimation of the variance components. We correct for the survival length bias by censoring the parent generation within each family at the time they attain the same cumulative hazard as the child generation, thus improving the validity of the estimates. Our finding that childhood shared environment in addition to genetic factors had a considerable effect on the development of melanoma is consistent with epidemiological studies.


Asunto(s)
Ambiente , Melanoma/etiología , Modelos Genéticos , Modelos Estadísticos , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Cocarcinogénesis , Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Melanoma/epidemiología , Melanoma/genética , Persona de Mediana Edad , Linaje , Suecia/epidemiología
18.
Disabil Rehabil ; 27(22): 1357-63, 2005 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-16372430

RESUMEN

PURPOSE: The study had two aims: (2) To explore whether knowledge about HIV and AIDS was similar among adolescents with disabilities compared with their non-disabled peers; and (2) To determine factors which may increase vulnerability of disabled adolescents to HIV infection and/or inappropriate access to HIV-related services. METHOD: A qualitative study using focus group discussions and sem-structured interviews was conducted with purposefully selected participants in Rwanda and Uganda. The participants included disabled adolescents, non-disabled adolescents, parents, teachers, members of disabled people's organisations and representatives of HIV/AIDS organisations. Interviews explored issues of HIV/AIDS knowledge, access to HIV/AIDS services and perceptions of personal risk. RESULTS: Barriers preventing adequate access to information about HIV and AIDS experienced by adolescents with disabilities depended on the nature and severity of the impairment. For example, parents and health workers were unable to communicate with deaf adolescents using sign language, adolescents with physical impairments were often unable to access community meetings about HIV and print material was not adapted for those with visual impairments. Further, assumptions by health workers and community members that people with disabilities were not sexually active led to the marginalisation of disabled people from HIV services. Adolescents with disability described low self-esteem and issues of self-efficacy affecting control of safer sexual relationships. A high level of targeted abuse, rape and exploitation was reported leading to vulnerability among this population. CONCLUSION: The impact of the HIV epidemic among people with disabilities is a neglected area. This study supports the need to develop strategies in HIV prevention programmes that include people with disabilities.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Personas con Discapacidad/psicología , Infecciones por VIH , Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Adolescente , Atención a la Salud , Grupos Focales , Infecciones por VIH/prevención & control , Humanos , Entrevistas como Asunto , Relaciones Padres-Hijo , Relaciones Profesional-Paciente , Población Rural , Rwanda , Uganda , Población Urbana
19.
Schizophr Res ; 80(2-3): 315-22, 2005 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-16125901

RESUMEN

Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n=49) and male patients with schizophrenia (n=90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM+/-0.10 vs. 1.06 nM+/-0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naïve, first episode patients (1.53 nM+/-0.19, n=37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM+/-0.17, n=34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM+/-0.10, n=19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease.


Asunto(s)
Ácido Quinurénico/líquido cefalorraquídeo , Esquizofrenia/líquido cefalorraquídeo , Adolescente , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
20.
Biocell ; 26(1): 25-33, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12058379

RESUMEN

Prosopis chilensis (Mol.) Stuntz (Algarrobo de Chile) is an important native tree species that can be grown in arid and semiarid regions for wood and forage production and environmental protection. Developing a simple and reliable in vitro protocol for cloning it would enable to improve it genetically. Explants of P. chilensis were taken from 4 months-old plants grown in the greenhouse or from adult trees grown in a natural environment. Nodal segments 1-2 cm long containing an axillary bud were selected from elongating shoots. These cuttings were aseptically cultured on two agar-solid basal media, MS or BTMm, and treated with 0.05 mg L-1 BA and 3 mg L-1 of either IAA, IBA or NAA. Sucrose (3% w/v) was used as carbon source. The percentage of sprouted cuttings and whole plant regeneration as well as its shoot and root length were recorded. Number, length and dry weight of shoots and roots were also measured. Rooting was successful with cuttings taken from young or adult plants, but explants from young plants showed a better response. Culturing in BTMm resulted in significantly greater shoot and root biomass than culturing in MS. Moreover, this response was higher in young explants when IBA was used as growth regulator. This paper reports a simple and effective method to micropropagate P. chilensis from young and adult plants.


Asunto(s)
Agricultura Forestal/métodos , Prosopis/crecimiento & desarrollo , Medios de Cultivo , Raíces de Plantas/crecimiento & desarrollo
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