96 resultados para Limited commitment
em BORIS: Bern Open Repository and Information System - Berna - Suiça
Resumo:
The paper aims to shed light on the role of communication in the European debt crisis. It examines the effects of public statements by ECB Governing Council members, EU officials and national representatives on the PIIGS' CDS and bond yield spreads. The focus lies on dovish statements that signal strong determination in the rescue of indebted countries, and hawkish statements that indicate limited commitment to support the PIIGS and protect its creditors. The analysis of daily data for the period between January 1, 2009 and August 12, 2011 in an EGARCH framework suggests that communication by representatives of Germany, France, and the EU as well as ECB Governing Council members had an immediate impact on both types of securities. No effects.
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Cyclin-dependent kinases (CDKs) successively phosphorylate the retinoblastoma protein (RB) at the restriction point in G1 phase. Hyperphosphorylation results in functional inactivation of RB, activation of the E2F transcriptional program, and entry of cells into S phase. RB unphosphorylated at serine 608 has growth suppressive activity. Phosphorylation of serines 608/612 inhibits binding of E2F-1 to RB. In Nalm-6 acute lymphoblastic leukemia extracts, serine 608 is phosphorylated by CDK4/6 complexes but not by CDK2. We reasoned that phosphorylation of serines 608/612 by redundant CDKs could accelerate phospho group formation and determined which G1 CDK contributes to serine 612 phosphorylation. Here, we report that CDK4 complexes from Nalm-6 extracts phosphorylated in vitro the CDK2-preferred serine 612, which was inhibited by p16INK4a, and fascaplysin. In contrast, serine 780 and serine 795 were efficiently phosphorylated by CDK4 but not by CDK2. The data suggest that the redundancy in phosphorylation of RB by CDK2 and CDK4 in Nalm-6 extracts is limited. Serine 612 phosphorylation by CDK4 also occurred in extracts of childhood acute lymphoblastic leukemia cells but not in extracts of mobilized CD34+ hemopoietic progenitor cells. This phenomenon could contribute to the commitment of childhood acute lymphocytic leukemia cells to proliferate and explain their refractoriness to differentiation-inducing agents.
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The characteristic features of Whipple's disease include abdominal pain, diarrhoea, wasting, and arthralgias, with the causative agent, Tropheryma whipplei, being detected mainly in intestinal biopsies. PCR technology has led to the identification of T. whipplei in specimens from various other locations, including the central nervous system and the heart. T. whipplei is now recognized as one of the causes of culture-negative endocarditis, and endocarditis can be the only manifestation of the infection with T. whipplei. Although it is considered a rare disease, the true incidence of endocarditis due to T. whipplei is not clearly established. With the increasing use of molecular methods, it is likely that T. whipplei will be more frequently identified. Questions also remain about the genetic variability of T. whipplei strains, optimal diagnostic procedures and therapeutic options. In the present study, we provide clinical data on four new patients with documented endocarditis due to T. whipplei in the context of the available published literature. There was no clinical involvement of the gastrointestinal tract. Genetic analysis of the T. whipplei strains with DNA isolated from the excised heart valves revealed little to no genetic variability. In a selected case, we describe acridine orange staining for early detection of the disease, prompting early adaptation of the antibiotic therapy. We provide long-term follow-up data on the patients. In our hands, an initial 2-week course of intravenous antibiotics followed by cotrimoxazole for at least 1 year was a suitable treatment option for T. whipplei endocarditis.
Resumo:
To analyze the dimensions and anatomic characteristics of the nasopalatine canal and the corresponding buccal bone plate of the alveolar process, using limited cone-beam computed tomography (CBCT) imaging.
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Context Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. Objectives To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. Design, Setting, and Participants Multicohort study of 632 patients >14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. Main Outcome Measures Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. Results The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for <80% vs ≥95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/μL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/μL vs 200/μL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. Conclusions Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.
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Nowadays, aerosol processes are widely used for the manufacture of nanoparticles (NPs), creating an increased occupational exposure risk of workers, laboratory personnel and scientists to airborne particles. There is evidence that possible adverse effects are linked with the accumulation of NPs in target cells, pointing out the importance of understanding the kinetics of particle internalization. In this context, the uptake kinetics of representative airborne NPs over 30 min and their internalization after 24 h post-exposure were investigated by the use of a recently established exposure system. This system combines the production of aerosolized cerium oxide (CeO(2)) NPs by flame spray synthesis with its simultaneous particle deposition from the gas-phase onto A549 lung cells, cultivated at the air-liquid interface. Particle uptake was quantified by mass spectrometry after several exposure times (0, 5, 10, 20 and 30 min). Over 35% of the deposited mass was found internalized after 10 min exposure, a value that increased to 60% after 30 min exposure. Following an additional 24 h post-incubation, a time span, after which adverse biological effects were observed in previous experiments, over 80% of total CeO(2) could be detected intracellularly. On the ultrastructural level, focal cerium aggregates were present on the apical surface of A549 cells and could also be localized intracellularly in vesicular structures. The uptake behaviour of aerosolized CeO(2) is in line with observations on cerium suspensions, where particle mass transport was identified as the rate-limiting factor for NP internalization.
Resumo:
Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.
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Several studies have documented women's use of vaginal practices in South Africa to enhance their desirability to men. This article describes a little known practice of this kind among women in KwaZulu-Natal. It involves the use of small incisions in the genital area (and often abdomen and breasts) to introduce herbal substances, described as love medicines, into the body through the incisions. In-depth interviews were carried out with 20 key informants and 20 women, and eight focus group discussions with women and men, in a rural and urban site in 2005-06. A province-wide household survey was then conducted using a multi-stage cluster sample design among 867 women aged 18-60. Forty-two per cent of the women in the household survey had heard of genital incisions; only 3% had actually used them. The main motivation was the enhancement of sexual attractiveness and long-term partner commitment. It appears to be a very recent practice, but may be an extension of an older healing practice not involving the genitals. It was most prevalent among rural women aged 24-29 (although not significant), those with less education, and those who suspected their partners of having other partners. It is linked to the modern popularity of love medicines, which in turn illustrates the troubling state of gender relations in KwaZulu-Natal today.
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To assess retrospectively the frequency and location of mandibular lingual foramina and their bony canals with limited cone-beam computed tomography.
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The purpose of the present study was to evaluate the detectability and dimensions of periapical lesions, the relationship of the mandibular canal to the roots of the respective teeth, and the dimension of the buccal bone by using limited cone-beam computed tomography (CBCT) in comparison to conventional periapical (PA) radiographs for evaluation of mandibular molars before apical surgery.
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Background: Women worldwide use various vaginal practices to clean or modify their vulva and vagina. Additional population-level information is needed on prevalence and motivations for these practices, characteristics of users, and their adverse effects. Methods: This was a household survey using multistage cluster sampling in Tete, Mozambique; KwaZulu-Natal, South Africa; Yogyakarta, Indonesia; and Chonburi, Thailand. In 2006–2007, vaginal practices and their motivations were examined using structured interviews with women 18–60 years of age (n=3610). Results: Prevalence, frequency, and motivations varied markedly. Two thirds of women in Yogyakarta and Chonburi reported one or more practices. In Yogyakarta, nearly half ingest substances with vaginal effects, and in Chonburi, external washing and application predominate. In Tete, half reported three or four current practices, and a quarter reported five or more practices. Labial elongation was near universal, and 92% of those surveyed cleanse internally. Two third's in KwaZulu-Natal practiced internal cleansing. Insertion of traditional solid products was rare in Chonburi and Yogyakarta, but one tenth of women in KwaZulu-Natal and nearly two thirds of women in Tete do so. Multivariate analysis of the most common practice in each site showed these were more common among less educated women in Africa and young urban women in Asia. Explicit sexual motivations were frequent in KwaZulu-Natal and Tete, intended for pleasure and maintaining partner commitment. Practices in Chonburi and Yogyakarta were largely motivated by femininity and health. Genital irritation was common at African sites. Conclusions: Vaginal practices are not as rare, exotic, or benign as sometimes assumed. Limited evidence of their biomedical consequences remains a concern; further investigation of their safety and sexual health implications is warranted.