Agents and intermediaries

Managing Football is the first book to directly respond to the rapid managerial, commercial and global development of the sport and offers a thorough analysis of how the football industry can meet the challenges that flow from these developments. Expertly edited by two well known specialists in football business management, it draws together the work of a world-class contributor team to form a comprehensive analysis of the most important issues facing the managers of football businesses across the world. The cutting edge analysis examines all the important business challenges in the football industry and the management of football businesses and covers all of the key football markets including England, Spain, France, Italy, Germany, Australia, North America, China, South Africa, South Korea, the Netherlands & Belgium, and Mexico. Managing Football is simply a must-read for anyone studying or working in football business management and is set to be an important landmark in this rapidly moving and globally expansive field.

Current multiple myeloma treatment strategies with novel agents: a European perspective.

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Les connectivites: progrès thérapeutiques et place de la biothérapie [Connective tissue diseases: news in therapy, role of biologics agents].

Systemic lupus erythematosus and primary Sjögren's syndrom are the two major connective tissue diseases. A better knowledge of their physiopathology allows us today to propose an adapted therapy. Moreover progress concerns the oldest treatment, hydroxychloroquine, and biotherapy. Hydroxychloroquine is still an actual treatment for lupus, its positive effects are better understood today. Nevertheless it does not seem to be efficient to treat primitive Sjögren. Biotherapy targeting B lymphocytes seems efficient in these two connective tissue diseases. Anti TNF therapy is not recommended and seems to induce connective tissue diseases. The real news is the recent approval and reimbursement in Switzerland of the new drug belimumab (Benlysta) in case of moderate lupus.

Supervision of Community Health Agents in the Family Health Strategy: the perspective of nurses

Objective Analyzing the conceptions of supervision of nurses in the Family Health Strategy (ESF - Estratégia Saúde da Família) in relation to community health workers (ACS – Agente Comunitário de Saúde), taking for reference the work process and the power relations. Method A qualitative study, in which 18 interviews were carried out with nurses from the ESF in the countryside of the state of Goiás. Following transcription, the data were subjected to thematic content analysis and the following categories were identified: Supervision with that sees it all and Supervision is participating and working together. Results Among the findings, it is clear the character of control and monitoring that is carried out primarily through printed instruments and home visits, which constitute vertical and impositive relations, and suffer influence of the local health management. Another finding is the supervision as acting together and with the educational perspective. Conclusion The supervision carried out does not provide the changes intended by the ESF.

Strategies for the development of tdm for targeted anticancer agents

Most of the novel targeted anticancer agents share classical characteristics that define drugs as candidates for blood concentration monitoring: long-term therapy; high interindividual but restricted intraindividual variability; significant drug-drug and drug- food interactions; correlations between concentration and efficacy/ toxicity with rather narrow therapeutic index; reversibility of effects; and absence of early markers of response. Surprisingly though, therapeutic concentration monitoring has received little attention for these drugs despite reiterated suggestions from clinical pharmacologists. Several issues explain the lack of clinical research and development in this field: global tradition of empiricism regarding treatment monitoring, lack of formal conceptual framework, ethical difficulties in the elaboration of controlled clinical trials, disregard from both drug manufacturers and public funders, limited encouragement from regulatory authorities, and practical hurdles making dosage adjustment based on concentration monitoring a difficult task for prescribers. However, new technologies are soon to help us overcome these obstacles, with the advent of miniaturized measurement devices able to quantify circulating drug concentrations at the point-of-care, to evaluate their plausibility given actual dosage and sampling time, to determine their appropriateness with reference to therapeutic targets, and to advise on suitable dosage adjustment. Such evolutions could bring conceptual changes into the clinical development of drugs such as anticancer agents, while increasing the therapeutic impact of population PK-PD studies and systematic reviews. Research efforts in that direction from the clinical pharmacology community will be essential for patients to receive the greatest benefits and the least harm from new anticancer treatments. The example of imatinib, the first commercialized tyrosine kinase inhibitor, will be outlined to illustrate a potential research agenda for the rational development of therapeutic concentration monitoring.

Social representation of domestic violence against women among Nursing Technicians and Community Agents

OBJECTIVE To analyze the social representations of the Nursing Technicians and Community Health Agents about domestic violence against women. METHOD A qualitative study carried out in the city of Rio Grande, RS, in which evocations and interviews were collected between July and November 2013. For the treatment of data were used the EVOC 2005 software and the context analysis. RESULT It is a structured representation, in which the central nucleus contains conceptual, imaging and attitudinal elements, namely: abuse, aggression, physical aggression, cowardice and lack of respect. Such terms were present in the context of the interviews. The professionals acknowledged that violence is not limited to physical aspects and were judgemental about the acts of the aggressor. CONCLUSION This knowledge may enable the problematization of the studied phenomenon with the team, and facilitate the search for prevention and intervention strategies for victims, offenders and managers of health services.

Bedrock Geologic Map of Iowa, 1998

Geologic map of Iowa in 1998

Land Cover Map of Iowa, 1999

Land Cover of Iowa in 1999

A novel vasopressin-induced transcript promotes MAP kinase activation and ENaC downregulation.

In the principal cell of the renal collecting duct, vasopressin regulates the expression of a gene network responsible for sodium and water reabsorption through the regulation of the water channel and the epithelial sodium channel (ENaC). We have recently identified a novel vasopressin-induced transcript (VIT32) that encodes for a 142 amino acid vasopressin-induced protein (VIP32), which has no homology with any protein of known function. The Xenopus oocyte expression system revealed two functions: (i) when injected alone, VIT32 cRNA rapidly induces oocyte meiotic maturation through the activation of the maturation promoting factor, the amphibian homolog of the universal M phase trigger Cdc2/cyclin; and (ii) when co-injected with the ENaC, VIT32 cRNA selectively downregulates channel activity, but not channel cell surface expression. In the kidney principal cell, VIP32 may be involved in the downregulation of transepithelial sodium transport observed within a few hours after vasopressin treatment. VIP32 belongs to a novel gene family ubiquitously expressed in oocyte and somatic cells that may be involved in G to M transition and cell cycling.

Research recommendations for selected IARC-classified agents.

OBJECTIVES: There are some common occupational agents and exposure circumstances where evidence of carcinogenicity is substantial but not yet conclusive for humans. The objectives are to identify research gaps and needs for twenty agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: A systematic review was conducted of new data published since the most recent pertinent IARC monograph meeting. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.[Authors]

Map of homicides by firearms: profile of the victims and the assaults

AbstractOBJECTIVEDescribing the profile of victims and assaults by gunshot, where the outcome was death.METHODAn ecological study conducted in the city of Maceió/AL, in 2012. Data were collected from the death statements. The variables studied were: the death circumstances, gender, age, marital status, place, date, time, month and proportion according to the occurring neighborhood.RESULTSThe homicide mortality rate was 65.2 per 100,000 inhabitants, with 130.6 per 100,000 men and 7.8 per 100,000 women. Of the total number of homicides, 93.6% of the victims were men. The age group between 15 and 29 years of age was the most affected, with 68.8%. In 97.6% of cases the death occurred at the site of aggression, 74.1% in the streets. In relation to the date, 54.2% of cases occurred between Friday and Sunday. 59.7% of the homicides were concentrated in seven neighborhoods.CONCLUSIONThe map of violence presented shows heterogeneous areas for the occurrence of assaults with firearms, characterizing the existing urban inequality in violence distribution.

Efficacy of PI3K pathway inhibitors as single agents in metastatic breast cancer

L’objectiu del cribatge molecular és seleccionar pacients que es beneficiïn especialment de teràpies dirigides. S’analitza l’activitat en monoteràpia de fàrmacs inhibidors de la via de PI3K/AKT/mTOR (PI3Ki) en pacients amb càncer de mama metastàtic (CMM) i s’exploren potencials predictors de benefici clínic. La mitjana de temps a la progressió és de 2.6 mesos en 38 pacients incloses. No existeix correlació entre alteracions de la via i l’eficàcia, excepte en pacients amb mutació de PIK3CA que van millor al tractar-se amb un PI3Ki alfa-especific. Aquests resultats emfatitzen la necessitat d’un adequat cribatge molecular previ al tractament amb teràpies dirigides en CMM