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The integration of optoelectronic devices, such as transistors and photodetectors (PDs), into wearables and textiles is of great interest for applications such as healthcare and physiological monitoring. These require flexible/wearable systems adaptable to body motions, thus materials conformable to non-planar surfaces, and able to maintain performance under mechanical distortions. Here, fibre PDs are prepared by combining rolled graphene layers and photoactive perovskites. Conductive fibres (~500 Ωcm-1) are made by rolling single-layer graphene (SLG) around silica fibres, followed by deposition of a dielectric layer (Al2O3 and parylene C), another rolled SLG as a channel, and perovskite as photoactive component. The resulting gate-tunable PD has a response time~9ms, with an external responsivity~22kAW-1 at 488nm for a 1V bias. The external responsivity is two orders of magnitude higher, and the response time one order of magnitude faster, than state-of-the-art wearable fibre-based PDs. Under bending at 4mm radius, up to~80% photocurrent is maintained. Washability tests show~72% of initial photocurrent after 30 cycles, promising for wearable applications.
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OBJECTIVE: This research explores absence seizures using data recorded from different layers of somatosensory cortex of four genetic absence epilepsy rats from Strasbourg (GAERS). Localizing the active layers of somatosensory cortex (spatial analysis) and investigating the dynamics of recorded seizures (temporal analysis) are the main goals of this research. APPROACH: We model the spike discharges of seizures using a generative spatio-temporal model. We assume that there are some states under first-order Markovian model during seizures, and each spike is generated when the corresponding state is activated. We also assume that a few specific epileptic activities (or atoms) exist in each state which are linearly combined and form the spikes. Each epileptic activity is described by two characteristics: (1) its spatial topography which shows the organization of current sources and sinks generating the epileptic activity, and (2) its temporal representation which illustrates the activation function of the epileptic activity. We show that the estimation of the model parameters, i.e. states and their epileptic activities (atoms), is similar to solving a dictionary learning problem for sparse representation. Instead of using classical dictionary learning algorithms, a new approach, taking into account the Markovian nature of the model, is proposed for estimating the models parameters, and its efficiency is experimentally verified. MAIN RESULTS: Experimental results show that there are one dominant and one unstable state with two epileptic activities in each during the seizures (temporal analysis). It is also found that the top and bottom layers of the somatosensory cortex are the most active layers during seizures (spatial analysis). The structural model is similar for all rats with a spatial topography which is the same for all rats but a temporal activation which changes according to the rat. SIGNIFICANCE: The proposed framework can be applied on any database acquired from a small area of the brain, and can provide valuable spatio-temporal analysis for neuroscientists.
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Aprendizaje Automático , Convulsiones/fisiopatología , Fenómenos Electrofisiológicos , Humanos , Modelos Neurológicos , Convulsiones/diagnóstico , Análisis Espacio-TemporalRESUMEN
PURPOSE OF INVESTIGATION: In Iran, the authors use neoadjuvant chemotherapy (NACT) prior to surgery in cervical cancer due to limited access to the radiotherapy and very prolonged waiting time in accession to radiotherapy. The study was done to analyze the efficacy of the NACT with high dose-dense paclitaxel and cisplatin before radical surgery on cure rate, survival rate, and the progression of free survival rate of bulky tumor of cervical cancer in Stages 1B2, IId A2, and IIB. MATERIALS AND METHODS: Fifty-two patients with cervical cancer in Stages Ib2, IIA2, and IIB were selected, and responding patients to chemotherapy were scheduled to undergo radical hysterectomy and bilateral pelvic lymphadenectomy with or without para-aortic lymphadenectomy. RESULTS: Fifty out of 52 patients with a median age of 50 years were evaluable for clinical response. Thirty-two patients (64%) responded to the NACT including six (12%) with a complete clinical response. There was no statistical relationship between clinical response, tumor stage and size, and parametrical involvement, however, patients with higher grade of tumor, adenocarcinoma or tumor in upper 2/3 of vagina showed a higher probability of no response to chemotherapy. Downstaging after NACT in all stages was statistically significant regarding pathologic findings and clinical response (p = 0.002). Five-year survival was 88% and factors affecting survival and disease-free survival were pathological response and tumor site based on cox-regression analysis. Overall recurrence rate was 20% and tumor size was the only significant relevant factor for recurrence (p = 0.017). CONCLUSION: Combined regimen of chemotherapy in locally advanced cervical cancer proved to be valuable and efficacious without any late complications.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Modelos de Riesgos Proporcionales , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
We proposed and demonstrated the first account of large-area, semi-transparent, tandem photosensitive nanocrystal skins (PNSs) constructed on flexible substrates operating on the principle of photogenerated potential buildup, which avoid the need for applying an external bias and circumvent the current-matching limitation between junctions. We successfully fabricated and operated the tandem PNSs composed of single monolayers of colloidal water-soluble CdTe and CdHgTe nanocrystals (NCs) in adjacent junctions on a Kapton polymer tape. Owing to the usage of a single NC layer in each junction, noise generation was significantly reduced while keeping the resulting PNS films considerably transparent. In each junction, photogenerated excitons are dissociated at the interface of the semi-transparent Al electrode and the NC layer, with holes migrating to the contact electrode and electrons trapped in the NCs. As a result, the tandem PNSs lead to an open-circuit photovoltage buildup equal to the sum of those of the two single junctions, exhibiting a total voltage buildup of 128.4 mV at an excitation intensity of 75.8 µW cm(-2) at 350 nm. Furthermore, we showed that these flexible PNSs could be bent over 3.5 mm radius of curvature and cut out in arbitrary shapes without damaging the operation of individual parts and without introducing any significant loss in the total sensitivity. These findings indicate that the NC skins are promising as building blocks to make low-cost, flexible, large-area UV/visible sensing platforms with highly efficient full-spectrum conversion.
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In the present study, different amounts of graphene nanosheets (GNSs) were added to the 4043 aluminum alloy powders by using the mechanical alloying method to produce the composite filler wires. With each of the produced composite filler wires, one all-weld metal coupon was welded using the gas tungsten arc (GTA) welding process. The microstructure, mechanical properties and fracture surface morphology of the weld metals have been evaluated and the results are compared. As the amount of GNSs in the composition of filler wire is increased, the microstructure of weld metal was changed from the dendritic structure to fine equiaxed grains. Furthermore, the tensile strength and microhardness of weld metal was improved, and is attributed to the augmented nucleation and retarded growth. From the results, it was seen that the GNSs/Al composite filler wire can be used to improve the microstructure and mechanical properties of GTA weld metals of aluminum and its alloys.
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The effect of multi-walled carbon nanotube (MWCNT) on the mechanical properties of aluminum multipass weld metal prepared by the tungsten inert gas (TIG) welding process was investigated. High energy ball milling was used to disperse MWCNT in the aluminum powder. Carbon nanotube/aluminum composite filler metal was fabricated for the first time by hot extrusion of ball-milled powders. After welding, the tensile strength, microhardness and MWCNT distribution in the weld metal were investigated. The test results showed that the tensile strength and microhardness of weld metal was greatly increased when using the filler metal containing 1.5 wt.% MWCNT. Therefore, according to the results presented in this paper, it can be concluded that the filler metal containing MWCNT can serve as a super filler metal to improve the mechanical properties of TIG welds of Al and its alloys.
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UNLABELLED: Ninety-three health care workers (HCW) in the Tokombere sahelian district volunteered to participate in a trial to investigate viral markers of hepatitis B, C, and D and HB vaccination status. METHODS: . Sera were tested using the Vikia HBsAg kit followed by CMIA for detection of HBsAg, anti-HBs, anti-HBc, and anti-HCV. HBsAg-positive HCW were tested for HBV-DNA, anti-HDV, and, if positive for anti-HDV, HDV-RNA. RESULTS: Analysis of anti-HBc positivity indicated that 91% of HCW had been infected by HBV, regardless of vaccination history. Vikia HBsAg results were confirmed by chemiluminescent microparticle immunoassay (CMIA) in all HCW and were positive in 17 HCW with virus load >2000 IU/mL in 6 and HDV co-infection in 6. Anti-HCV was found in 6 HCW. Among the 55 HCW that had not been vaccinated, only 3 needed vaccination because of anti-HBc negativity. Among HCW considered for HBV treatment, one patient presenting HBV/HDV co-infection was excluded after diagnosis of hepatocarcinoma. CONCLUSION: Systematic HB vaccination of new HCW appears unnecessary in this rural region of Africa. Anti-HBc screening is cost-effective for identifying HCW requiring vaccination. Vikia HBsAg is effective for point-of-care screening. We underline the need for universal early (preferably neonatal) HB vaccination and for availability of anti-HBV drug in limited-resource countries.
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Biomarcadores/sangre , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/sangre , Hepatitis C/sangre , Hepatitis D/sangre , Grupo de Atención al Paciente , Población Rural/estadística & datos numéricos , Camerún/epidemiología , Hepatitis B/diagnóstico , Hepatitis B/inmunología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis C/diagnóstico , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis D/diagnóstico , Hepatitis D/inmunología , Humanos , Factores Inmunológicos/sangre , Vigilancia de la Población , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Vacunación/métodos , Vacunación/estadística & datos numéricos , Vacunas contra Hepatitis Viral/administración & dosificaciónRESUMEN
INTRODUCTION: Cytoreductive surgery is a pivotal component of primary treatment in patients with ovarian epithelial caner (OEC) and several studies have shown better outcomes of optimal debulking. The aim of this prospective study was to determine if optimum versus suboptimal cytoreductive surgery predicts CA125 levels two weeks after surgery. MATERIAL AND METHODS: Sixty patients with epithelial ovarian cancer scheduled for cytoreductive surgery in Imam Khomeini Hospital, Tehran, Iran were enrolled in this study. Two groups of patients were to undergo optimal or suboptimal cytoreductive surgery. Optimal cytoreduction was defined as the largest volume of residual disease < 1 cm in maximal dimension. CA125 levels were measured in all patients preoperatively and at two, seven and 14 days after surgery. CA125 levels were converted to a log scale. RESULTS: The distribution of staging, grading and types of tumors in each group were statistically equal but insignificant (chi square). The difference in mean of CA125 before and two weeks after surgery was statistically significant (paired t-test; p = 0.0001) but the grade, stage and type of tumors did not have any impact on CA125 regression. However, regression of CA125 two weeks after the operation did not differ statistically between the optimal and suboptimal cytoreduction groups (repeated measure ANOVA). CONCLUSION: Although, postoperative CA125 decreased significantly in two weeks after tumor cytoreduction in patients with epithelial ovarian cancer, its regression did not differ according to optimal or suboptimal groups.
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Antígeno Ca-125/sangre , Proteínas de la Membrana/sangre , Neoplasias Glandulares y Epiteliales/sangre , Neoplasias Ováricas/sangre , Adulto , Anciano , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/cirugía , Valor Predictivo de las Pruebas , Estudios Prospectivos , Resultado del TratamientoRESUMEN
To analyze the genetic diversity of the NS3 gene in patients infected with hepatitis C virus (HCV) genotype 4 (HCV-4) and to assess the possible effects of the gene polymorphism (or variability) on drug susceptibility, 43 NS3 gene sequences were determined for 53 selected patients with HCV-4 infection. NS3 sequencing, like NS5B sequencing, allowed correct subtype determination. Most residues that were located within the catalytic triad or the NS4-binding region or that were involved in metal binding were highly conserved and identical to those found in HCV genotype 1. Compared with HCV genotype 1, all HCV-4 NS3 protein presented V36L and C16T residue changes that could potentially reduce antiprotease activity. The efficacy of antiprotease in HCV-4-infected patients remains to be proven in large clinical trials.
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Antivirales/uso terapéutico , Genotipo , Hepacivirus/genética , Proteínas no Estructurales Virales/genética , Secuencia de Aminoácidos , Antivirales/administración & dosificación , Regulación Viral de la Expresión Génica/fisiología , Variación Genética , Hepacivirus/clasificación , Humanos , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismoRESUMEN
We have recently identified (Akhavan S et al., Thromb Haemost 2000; 84: 989-97) a patient with a mild bleeding diathesis associated to an homozygous mutation in the thrombin B chain (Gly25Ser, chymotrypsinogen numbering, i.e. position 330 in human prothrombin numbering). Transient transfection of wild-type prothrombin (FII-WT) and mutant prothrombin (designated FII-G25(330)S) cDNA in COS-7 cells showed a mild reduction (50%) in FII-G25(330)S production. Recombinant proteins, stably expressed in Chinese hamster ovary cells, were isolated and activated by Taipan snake or Echis carinatus venoms. We show that the G25(330)S mutation results in a decrease in the rate of prothrombin proteolytic activation. The mutation also significantly decreases (i) the catalytic activity of thrombin with a 9-fold reduction in catalytic efficiency of the mutant toward S-2238; (ii) the interaction with benzamidine; (iii) the rate of inhibition by TLCK and antithrombin; and (iv) the rate of hydrolysis of macromolecular substrates (fibrinogen, protein C). In contrast, exosite I does not appear to be affected by the molecular defect. These results, together with molecular modeling and dynamics, indicate that Gly25(330) is important for proper expression and probably proper folding of prothrombin, and also plays a critical role in both the alignment of the catalytic triad and the flexibility of one of the activation segments of prothrombin.
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Glicina/química , Trombina/química , Animales , Sitios de Unión , Células CHO , Células COS , Catálisis , Cricetinae , Análisis Mutacional de ADN , ADN Complementario/metabolismo , Fibrina/química , Fibrinógeno/química , Homocigoto , Humanos , Hidrólisis , Cinética , Modelos Moleculares , Mutación , Conformación Proteica , Estructura Terciaria de Proteína , Protrombina/química , Protrombina/genética , Proteínas Recombinantes/química , Venenos de Serpiente , Serpientes , Trombina/antagonistas & inhibidores , Factores de Tiempo , TransfecciónRESUMEN
UNLABELLED: Deficiencies of coagulation factors (other than factor VIII and factor IX) that cause a bleeding disorder are inherited as autosomal recessive traits and are generally rare, with prevalences in the general population varying between 1 : 500 000 and 1 : 2 000 000. In the last few years, the number of patients with recessively transmitted coagulation deficiencies has increased in European countries with a high rate of immigration of Islamic populations, because in these populations, consanguineous marriages are frequent. Owing to the relative rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects and the actual management of bleeding episodes are not as well established as for haemophilia A and B. This article reviews these disorders in terms of their clinical manifestations and characterization of the molecular defects involved. The general principles of management are also discussed. KEYWORDS: afibrinogenaemia, autosomal recessive disorders, factor VIII, factor XI, factor XIII.
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Trastornos de las Proteínas de Coagulación/genética , Factores de Coagulación Sanguínea/genética , Factores de Coagulación Sanguínea/uso terapéutico , Trastornos de las Proteínas de Coagulación/diagnóstico , Trastornos de las Proteínas de Coagulación/etiología , Genes Recesivos , Hemofilia A , Humanos , MutaciónRESUMEN
We have identified a novel polymorphism located in intron 1a of the human factor VII gene, caused by the nucleotide change G to A at position + 73. In a population of 128 healthy individuals from northern Italy, the variant A73 allele had a frequency of 0.21, whereas the frequency of the previously reported 10 bp insertion allele located at -323 in the promoter region was 0.17 and that of the Q353 allele in the catalytic region of the factor VII gene was 0. 20. In 75% of the healthy individuals, the A73 allele was present together with the 10 bp insertion and the Q353 alleles, indicating a strong linkage disequilibrium. The concomitant presence of A73 with both the 10 bp and the Q353 alleles was associated with the lowest factor VII levels, measured as coagulant activity, activated factor VII and factor VII antigen. The G73A polymorphism was also evaluated in 190 survivors of myocardial infarction who had experienced the event before the age of 45 years and in 179 individuals with a negative exercise test matched with patients for sex, age and geographical origin. Patients carrying the A73 allele associated with lower factor VII levels tended to have a lower risk of myocardial infarction (adjusted odds ratio 0.54; 95% confidence intervals 0.29-0.99). In conclusion, we found a novel variant allele in intron 1a of the human factor VII gene that is often associated in healthy individuals with the 10 bp and Q353 alleles in the promoter and catalytic region of the same gene. This intronic mutation, alone or in association with other factor VII gene polymorphisms, might confer protection against myocardial infarction in the young.
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Factor VII/genética , Infarto del Miocardio/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Femenino , Genotipo , Heterocigoto , Homocigoto , Humanos , Italia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangreRESUMEN
Prothrombin deficiency is an autosomal recessive disorder associated with a moderately severe bleeding tendency. In this study, 13 patients with prothrombin deficiency were screened for the presence of alterations in the prothrombin gene, and nine novel candidate mutations were identified. Of 11 patients with hypoprothrombinemia, ten are homozygous for five mutations and one patient is a compound heterozygote. The two patients with dysprothrombinemia are homozygous for two mutations. Eight of nine mutations are missense ones associated with single amino acid substitutions in the propeptide (Arg-1Gln, Arg-2Trp), the kringle-1 (Asp118Try) and kringle-2 (Arg220Cys) domains and the catalytic serine protease domain (Gly330Ser, Ser354Arg. Arg382His and Arg538Cys). The ninth mutation is an in-frame deletion of 3 bp that results in the omission of one amino acid (del Lys 301/302). The combination of these missense mutations with crystal structures for alpha-thrombin and the prothrombin fragments 1 and 2 resulted in new insight into the function of alpha-thrombin. The hypoprothrombinemia mutations were inferred to affect either the cleavage of the propeptide from the Gla domain, the stability of the kringle-1 and -2 domains, or the close association of the A and B chains of the serine protease domain. The dysprothrombinemia mutations were inferred to directly affect catalytic function through their location at the active site crevice or exosite 1 within the serine protease domain.
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Hipoprotrombinemias/genética , Mutación/genética , Protrombina/química , Adolescente , Adulto , Secuencia de Aminoácidos , Dominio Catalítico , Niño , Cristalografía por Rayos X , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Modelos Moleculares , Datos de Secuencia Molecular , Fenotipo , Estructura Terciaria de Proteína , Protrombina/genética , Alineación de Secuencia , Trombina/químicaRESUMEN
The molecular defect of a congenitally dysfunctional form of prothrombin, prothrombin Segovia, was identified in a patient with a severe bleeding tendency, reduced prothrombin coagulant activity, and normal antigen level. Nucleotide sequencing of amplified DNA revealed a G --> A change at nucleotide 7539 of exon 9 of the prothrombin gene. This resulted in the substitution of Gly319 by Arg. The proband was homozygous for this mutation, his father and brother were heterozygous. We surmised that the substitution, which occurs near the site of cleavage of prothrombin by factor Xa (Arg320-Ile321), altered the conformation of the protein making the cleavage site inaccessible.
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Sustitución de Aminoácidos/genética , Trastornos Hemorrágicos/genética , Protrombina/genética , Adulto , Humanos , Masculino , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Single-point mutations in the gene coding for prothrombin (factor II:A20210) or factor V (factor V:A1691) are associated with an increased risk of venous thromboembolism. The use of oral contraceptives is also a strong and independent risk factor for the disease, and the interaction between factor V:A1691 and oral contraceptives greatly increases the risk. No information is available about the interaction between oral contraceptives and mutant prothrombin. We investigated 148 women with a first, objectively confirmed episode of deep vein thrombosis and 277 healthy women as controls. Fourteen patients (9.4%) were carriers of factor II:A20210, 24 (16.2%) of factor V:A1691, and 4 (2.7%) of both defects. Among controls, the prevalence was 2.5% for either factor II:A20210 or factor V:A1691, and there was no carrier of both the mutations. The relative risk of thrombosis was 6-fold for factor II:A20210 and 9-fold for factor V:A1691. The most prevalent circumstantial risk factor in patients and the only one observed in controls was oral contraceptive use, which per se conferred a 6-fold increased risk of thrombosis. The risk increased to 16.3 and 20.0 when women with factor II:A20210 or factor V:A1691 who used oral contraceptives were compared with noncarriers and nonusers. These figures indicate a multiplicative interaction between the genetic risk factors and oral contraceptives. No difference in the type of oral contraceptives was observed between patients and controls, those of third generation being the most frequently used (73% and 80%). We conclude that carriers of the prothrombin mutation who use oral contraceptives have a markedly increased risk of deep vein thrombosis, much higher than the risk conferred by either factor alone.
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Anticonceptivos Orales/administración & dosificación , Factor V/genética , Mutación Puntual , Protrombina/genética , Trombosis de la Vena/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Genotipo , Heterocigoto , Homocigoto , Humanos , Persona de Mediana Edad , Factores de Riesgo , Trombosis de la Vena/inducido químicamente , Trombosis de la Vena/epidemiologíaRESUMEN
Clinical laboratories are at present confronted with increasing demands for thrombophilia work-up, which may seriously overwhelm their capacity. Recently, methods able to investigate the protein C anticoagulant pathway globally have been proposed. In this study we investigated the reliability of one such method for its ability to detect patients with known defects of the pathway by testing plasmas from patients with the FVQ506 mutation, with congenital protein C, protein S or antithrombin deficiencies, and patients with previous history of thrombosis, but no identifiable defects. The results show that the new global test fulfils the requirements for congenital protein C deficiency and activated protein C resistance associated with the FVQ506 mutation, which account for more than half of the congenital defects found in thrombophilia. However, congenital protein S deficiency very often remains undetected by this test. Improvement of sensitivity toward this component of the protein C anticoagulant pathway would enroll the global test as a suitable candidate to explore the pathway. Since antithrombin, which also remains undetected by this test, is an additional important risk factor for venous thrombosis, devoting time and effort to developing global tests able to detect defects in both the antithrombin and protein C pathways is warranted.
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Deficiencia de Proteína C/genética , Proteína C/metabolismo , Trombofilia/diagnóstico , Trombofilia/genética , Resistencia a la Proteína C Activada/genética , Antitrombinas/deficiencia , Antitrombinas/genética , Análisis Mutacional de ADN , Factor V/genética , Humanos , Mutación , Proteína C/genética , Deficiencia de Proteína S/genética , Trombosis/genética , Trombosis de la Vena/genéticaRESUMEN
Using a behavioral high-risk two-site prospective design, we tested the cognitive vulnerability hypotheses about suicidality. Consistent with prediction, the high cognitive risk (HR) participants were more likely than the low cognitive risk (LR) participants to exhibit suicidality, measured by both structured diagnostic interview and questionnaire self-report, during the 2 1/2 year prospective follow-up period. Moreover, when the prospective period was examined as a whole, the mediation hypothesis derived from the cognitive theories was strongly supported. Hopelessness appeared to mediate the obtained relationship between cognitive vulnerability and suicidality. Finally, the obtained relationship between cognitive vulnerability and suicidality was not mediated by other hypothesized risk factors for suicidality not specified in the cognitive theories, such as past suicidality, personal history of depressive disorders, borderline and antisocial personality dysfunction, and parental history of depression.