917 resultados para Strategic document with primary focus on injury prevention in the home


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BACKGROUND: Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. METHODS/DESIGN: Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. DISCUSSION: Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345669.

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INTRODUCTION AND AIMS: The positive relationship between alcohol use, gender and violence-related injury is well established. However, less is known about injuries when alcohol is used in combination with other drugs. DESIGN AND METHODS: Self-report information was collected on alcohol and illicit drug use in the 6 h before a violence-related injury in probability samples of patients presenting to emergency departments (n = 9686). RESULTS: Patients with violence-related injuries reported the highest rates of alcohol use (49% of men; 23% of women) and alcohol use combined with illicit drugs (8% of men; 4% of women) whereas non-violent injury patients reported lower rates of alcohol use (17% of men; 8% of women) and alcohol use combined with drugs (2% for men; 1% for women). Marijuana/hashish was the most commonly reported drug. The odds of a violent injury were increased when alcohol was used [men: odds ratio (OR) = 5.4, 95% confidence interval (CI) 4.6-6.3; women: OR = 4.0, 95% CI 3.0-5.5] or when alcohol was combined with illicit drug use before the injury (men: OR = 6.6, 95% CI 4.7-9.3; women: OR = 5.7, 95% CI = 2.7-12.2) compared with non-users. No significant change in the odds of a violent injury was observed for men or women when alcohol users were compared with alcohol and drug users. DISCUSSION AND CONCLUSIONS: The positive association between alcohol and violent injury does not appear to be altered by the added use of drugs. Additional work is needed to understand the interpersonal, contextual and cultural factors related to substance use to identify best prevention practices and develop appropriate policies. [Korcha RA, Cherpitel CJ, Witbrodt J, Borges G, Hejazi-Bazargan S, Bond JC, Ye Y, Gmel G. Violence-related injury and gender: The role of alcohol and alcohol combined with illicit drugs. Drug Alcohol Rev 2014;33:43-50].

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This study examines the proportions of regenerative and collateral sprouting to the skin after peripheral nerve injury. Methods: In the first experimental paradigm, primary afferent neurones were pre-labelled with Diamidino Yellow (DY), injected in digit 3, followed by sciatic nerve section and repair. After three months of regeneration, digit 3 was re-injected with Fast Blue (FB) to label regernating cells. Fluoro-Gold (FG) was applied to the femoral (FEM) and musculocutaneous (MC) nervers four days later to quantify their contribution to the innveration. In the second experimental paradigm, sciatic nerve was first sectioned and repaired. Three months later, the sciatic was resected, and digit 3 injected with FB. After four more days, FEM and MC were resected and FG injected in all digits. Results: Neurones in dorsal root ganglion (DRG) L5 had a higher rate of correct reinnervation of digit 3 (44-72%) than neurones in DRG L4 (14-44%). Like in control cases, only occasional axons were traced from the FEM and MC. In the second experiment, only occasional labelled neurones appeared. Conclusions: The results indicate differences in the capacity for correct peripheral sensory reinnvervation between segmental levels and that in this model collateral sprouting was practically non-existent compared to regenerative sprouting.

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There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.

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Futures trading in Commodities has three specific economic functions viz. price discovery, hedging and reduction in volatility. Natural rubber possesses all the specifications required for futures trading. Commodity futures trading in India attained momentum after the starting of national level commodity exchanges in 2003. The success of futures trading depends upon effective price risk management, price discovery and reduced volatility which in turn depends upon the volume of trading. In the case of rubber futures market, the volume of trading depends upon the extent of participation by market players like growers, dealers, manufacturers, rubber marketing co-operative societies and Rubber Producer’s Societies (RPS). The extent of participation by market players has a direct bearing on their awareness level and their perception about futures trading. In the light of the above facts and the review of literature available on rubber futures market, it is felt that a study on rubber futures market is necessary to fill the research gap, with specific focus on (1) the awareness and perception of rubber futures market participants viz. (i) rubber growers, (ii) dealers, (iii) rubber product manufacturers, (iv) rubber marketing co-operative societies and Rubber Producer’s Societies (RPS) about futures trading and (2) whether the rubber futures market is fulfilling the economic functions of futures market viz. hedging, reduction in volatility and price discovery or not. The study is confined to growers, dealers, rubber goods manufacturers, rubber marketing co-operative societies and RPS in Kerala. In order to achieve the stated objectives, the study utilized secondary data for the period from 2003 to 2013 from different published sources like bulletins, newsletters, circulars from NMCE, Reserve Bank of India (RBI), Warehousing Corporation and traders. The primary data required for this study were collected from rubber growers, rubber dealers, RPS & Rubber Marketing Co-operative Societies and rubber goods manufacturers in Kerala. Data pertaining to the awareness and perception of futures trading, participation in the futures trading, use of spot and futures prices and source of price information by dealers, farmers, manufacturers and cooperative societies also were collected. Statistical tools used for analysis include percentage, standard deviation, Chi-square test, Mann – Whitney U test, Kruskal Wallis test, Augmented Dickey – Fuller test statistic, t- statistic, Granger causality test, F- statistic, Johansen co – integration test, Trace statistic and Max –Eigen statistic. The study found that 71.5 per cent of the total hedges are effective and 28.5 per cent are ineffective for the period under study. It implies that futures market in rubber reduced the impact of price risks by approximately 71.5 per cent. Further, it is observed that, on 54.4 per cent occasions, the futures market exercised a stabilizing effect on the spot market, and on 45.6 per cent occasions futures trading exercised a destabilizing effect on the spot market. It implies that elasticity of expectation of futures market in rubber has a predominant stabilizing effect on spot prices. The market, as a whole, exhibits a bias in favour of long hedges. Spot price volatility of rubber during futures suspension period is more than that of the pre suspension period and post suspension period. There is a bi-directional association-ship or bi-directional causality or pair- wise causality between spot price and futures price of rubber. From the results of the hedging efficiency, spot price volatility, and price discovery, it can be concluded that rubber futures market fulfils all the economic functions expected from a commodity futures market. Thus in India, the future of rubber futures is Bright…!!!

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Objectives: The main objective of this study was to investigate whether the interaction of malocclusion (open bite or increased overjet) combined with inadequate lip coverage strengthens its association with traumatic dental injury (TDI) in the primary teeth of preschool children compared to the presence of malocclusion alone. Subjects and methods: A cross-sectional survey was conducted with 376 children aged 3659 months who attended the National Day of Childrens Vaccination. Presence of TDI, tooth discoloration, and sinus tract were evaluated in the children. Variables associated with occlusion were also evaluated. A Poisson regression analysis was performed to verify the association between the explanatory variables and TDI as well as possible interactions among the variables. Then, the prevalence ratio was calculated. Results: The prevalence of TDI was 27.7%. The maxillary central incisor was the most affected tooth, without differences between the right and left sides. Boys had more dental trauma than girls (P = 0.04). The most common TDI was crown fracture restricted to the enamel (58.4%). Children with a combination of anterior open bite or increased overjet and inadequate lip coverage presented a higher prevalence of TDI than when the malocclusions were presented alone (P < 0.05). The same trends were observed when we included, in the final adjusted model, increased overjet instead of open bite. Conclusions: Anterior malocclusions of primary teeth such as increased overjet and anterior open bite are statistically significantly associated with dental trauma only when inadequate lip coverage is also present.

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This study aimed to identify age differences in the themes of songs written by patients with traumatic brain injury (TBI). Lyrics from 82 songs written by 11 female and 20 male patients aged between 5 and 60 years were categorised into eight themes and 24 categories. Incidence of categories and themes were calculated and compared across six age brackets. Results suggest that children, early adolescent, and middle adolescent patients with TBI focus on memories to a substantially greater degree than older patients. Early and late adolescent patient groups are most likely to be self-reflective, and to raise concerns about the future, when compared with other patient groups. (author abstract)

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This phenomenological study describes the impact of an educational intervention on the day-to-day experiences of older parent caregivers of adults with developmental disabilities who were engaged in the process of future-care planning. Qualitative strategies of individual and focus group interviewing were used with a purposive sample of older caregivers. Participants were members of an existing parent support group. Twenty-three caregivers representing 18 families were queried before and after the education program. The disabilities represented were mental retardation, cerebral palsy and autism. Parents whose children live at or away from home were included. The intervention was conducted on five Saturdays over a two month period; the duration of the study was five months. Findings used typical words of the respondents from their individual and focus group interviews to describe feelings, attitudes and experiences in making future-care plans. Data from verbatim transcriptions and researcher's field notes were coded, analyzed, sorted into themes, and subjected to interpretive analysis. Respondents showed a positive change in attitudes and actions after participating in the education program, regardless of their initial stage in care planning. Fears were replaced by hope and determination; hesitation and ineptitude by feelings of competence and confidence; and procrastination and delay by purposeful actions. Other key findings: use of a planning document greatly aided caregivers; barriers to planning were often intrinsic and amenable to education; residential plans were the most difficult aspect of planning; listening to the experiences of other parent caregivers was helpful; and making burial plans for their offspring was one aspect of planning parents wished to do themselves. ^

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A Non-Indigenous Species (NIS) is defined as an organism, introduced outside its natural past or present range of distribution by humans, that successfully survives, reproduces, and establish in the new environment. Harbors and tourist marinas are considered NIS hotspots, as they are departure and arrival points for numerous vessels and because of the presence of free artificial substrates, which facilitate colonization by NIS. To early detect the arrival of new NIS, monitoring benthic communities in ports is essential. Autonomous Reef Monitoring Structures (ARMS) are standardized passive collectors that are used to assess marine benthic communities. Here we use an integrative approach based on multiple 3-month ARMS deployment (from April 2021 to October 2022) to characterize the benthic communities (with a focus on NIS) of two sites: a commercial port (Harbor) and a touristic Marina (Marina) of Ravenna. The colonizing sessile communities were assessed using percentage coverage of the taxa trough image analyses and vagile fauna (> 2 mm) was identified morphologically using a stereomicroscope and light microscope. Overall, 97 taxa were identified and 19 of them were NIS. All NIS were already observed in port environments in the Mediterranean Sea, but for the first time the presence of the polychaete Schistomeringos cf. japonica (Annenkova, 1937) was observed; however molecular analysis is needed to confirm its identity. Harbor and Marina host significantly different benthic communities, with significantly different abundance depending on the sampling period. While the differences between sites are related to their different environmental characteristic and their anthropogenic pressures, differences among times seems related to the different life cycle of the main abundant species. This thesis evidenced that ARMS, together with integrative taxonomic approaches, represent useful tools to early detect NIS and could be used for a long-term monitoring of their presence.

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Com a crescente sensibilização mundial relativa ao aquecimento global, provocado pela alta quantidade de emissão de gases com efeito de estufa, torna-se imperativa a redução de consumos de combustíveis fósseis e consecutivas emissões. Ao nível da construção civil, uma intervenção eficaz na prevenção de perdas de ar aquecido poderá levar a diminuições superiores a 50% na utilização de energia. Este trabalho pretende estudar a importância da eficiência energética nos edifícios, com especial enfoque na sua permeabilidade ao ar. O ensaio de porta ventiladora permite avaliar esta permeabilidade e identificar os locais onde se dão as infiltrações, nomeadamente com auxílio da câmara térmica. O principal objectivo é estudar a aplicação deste ensaio na legislação em desenvolvimento no âmbito da certificação energética, através da comparação dos resultados de quatro habitações distintas. Também ao nível da eficiência energética, será obtida a classe energética, segundo a legislação em vigor à corrente data em Portugal, de uma das habitaçãoes ensaiadas e propostas medidas de melhoria para o desempenho energético desta. Do estudo efectuado é destacado o facto de o valor de renovações horárias do ar interior de uma fracção ser sempre inferior quando obtido unicamente através da legislação em desenvolvimento, em comparação com a obtenção deste através da legislação com auxílio do ensaio da porta ventiladora, o que leva a um grande desincentivo na utilização deste.

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This study seeks to perform a survey of patterns of practice among the different physicians involved in the bone metastases management, with special focus on external beam radiotherapy (EBRT).A questionnaire about bone metastases based on clinical cases and supplemented with general questions, including medical therapies, EBRT and metabolic radiotherapy strategies, surgery, and supportive care approaches, was sent to 4,706 French-speaking physicians in Belgium, France, Luxemburg, and Switzerland.Overall, 644 questionnaires were analyzed. Twenty-eight percent concerned the radiotherapy approach and were judged adequate to respond to the part dedicated to EBRT. Sixty-nine percent of physicians used a total dose irradiation of 30 Gy delivered in ten fractions. A large majority (75%) used two opposed fields prescribed at mid-depth (30%), or with non-equally weighted fields (45%). Seventy percent irradiated also above and below the concerned vertebra. A dosimetry planning treatment was done in 85% and high-energy megavoltage photons were used in 42%. Moreover, 54% physicians used short course radiotherapy in routine.Radiotherapy remains the mainstay of treatment of bone metastases, but there is substantial heterogeneity in clinical practice. Guidelines and treatment protocols are required to improve the treatment quality.

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Multiple myeloma is a monoclonal malignant proliferation of plasma cells that causes osteolytic lesions in the vertebrae, ribs, pelvic bone, skull and jaw. We report on a clinical case of an 81-year-old male patient who presented with a tumefaction in the mandibular symphysis region, which had evolved over the previous seven months. In the radiographic examination, an extensive osteolytic lesion was observed in the region mentioned above. An incisional biopsy was performed and a histopathological study revealed a malignant hematopoietic neoplasm formed by plasmacytoid cells. During the bone gammagraphy a dissemination of the disease was detected in the scapula, clavicle and ribs. The diagnosis was multiple myeloma. Knowledge about the maxillofacial manifestations of multiple myeloma is important for the early diagnosis of the disease, since its primary form can manifest itself in the jaw. In the clinical case presented here, we highlight the interdisciplinarity needed to obtain a diagnosis and treatment of multiple myeloma

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Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders.

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Abstract Introduction: Sepsis, an extremely prevalent condition in the intensive care unit, is usually associated with organ dysfunction, which can affect heart and kidney. Objective: To determine whether the cardiac dysfunction and the Troponin I forecast the occurrence of acute renal failure in sepsis. Methods: Cardiac dysfunction was assessed by echocardiography and by the serum troponin I levels, and renal impairment by AKIN criteria and the need of dialysis. Twenty-nine patients with incident sepsis without previous cardiac or renal dysfunction were enrolled. Results and Discussion: Patients averaged 75.3 ± 17.3 years old and 55% were male. Median APACHE II severity score at ICU admission was 16 (9.7 - 24.2) and mortality rate in 30 days was 45%. On the fifth day, 59% had ventricular dysfunction. Troponin serum levels on day 1 in the affected patients were 1.02 ± 0.6 ng/mL compared with 0.23 ± 0.18 ng/mL in patients without heart dysfunction (p = 0.01). Eighteen out of 29 patients (62%) underwent renal replacement therapy (RRT) and the percent of patients with ventricular dysfunction who required dialysis was higher (94% vs. 16%, p = 0.0001). Values of troponin at day 1 were used to develop a ROC curve to determine their ability to predict the need of dialysis. The area under the curve was 0.89 and the cutoff value was 0.4 ng/mL. Conclusion: We found that an elevation in serum troponin levels, while guarding a relationship with ventricular dysfunction, can be a precious tool to predict the need for dialysis in sepsis patients.

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This research project is a contribution to the global field of information retrieval, specifically, to develop tools to enable information access in digital documents. We recognize the need to provide the user with flexible access to the contents of large, potentially complex digital documents, with means other than a search function or a handful of metadata elements. The goal is to produce a text browsing tool offering a maximum of information based on a fairly superficial linguistic analysis. We are concerned with a type of extensive single-document indexing, and not indexing by a set of keywords (see Klement, 2002, for a clear distinction between the two). The desired browsing tool would not only give at a glance the main topics discussed in the document, but would also present relationships between these topics. It would also give direct access to the text (via hypertext links to specific passages). The present paper, after reviewing previous research on this and similar topics, discusses the methodology and the main characteristics of a prototype we have devised. Experimental results are presented, as well as an analysis of remaining hurdles and potential applications.