Appraising and selecting strategies to combat and mitigate desertification based on stakeholder knowledge and globalbest practices in Cape Verde Archipelago

Cape Verde is considered part of Sahelian Africa, where drought and desertification are common occurrences. The main activity of the rural population is rain-fed agriculture, which over time has been increasingly challenged by high temporal and spatial rainfall variability, lack of inputs, limited land area, fragmentation of land, steep slopes, pests, lack of mechanization and loss of top soil by water erosion. Human activities, largely through poor farming practices and deforestation (Gomez, 1989) have accelerated natural erosion processes, shifting the balance between soil erosion and soil formation (Norton, 1987). According to previous studies, vegetation cover is one of the most important factors in controlling soil loss (Cyr et al., 1995; Hupy, 2004; Zhang et al., 2004; Zhou et al., 2006). For this reason, reforestation is a touchstone of the Cape Verdean policy to combat desertification. After Independence in 1975, the Cape Verde government had pressing and closely entangled environmental and socio-economic issues to address, as long-term desertification had resulted in a lack of soil cover, severe soil erosion and a scarcity of water resources and fuel wood. Across the archipelago, desertification was resulting from a variety of processes including poor farming practices, soil erosion by water and wind, soil and water salinity in coastal areas due to over pumping and seawater intrusion, drought and unplanned urbanization (DGA-MAAP, 2004). All these issues directly affected socio-economic vulnerability in rural areas, where about 70% of people depended directly or indirectly on agriculture in 1975. By becoming part of the Inter- State Committee for the Fight against Drought in the Sahel in 1975, the government of Cape Verde gained structured support to address these issues more efficiently. Presentday policies and strategies were defined on the basis of rational use of resources and human efforts and were incorporated into three subsequent national plans: the National Action Plan for Development (NDP) (1982–1986), the NDP (1986–1990) and the NDP (1991–1995) (Carvalho

Therapeutic potential of endothelin receptor modulators: lessons from human clinical trials.

The endothelin system, and in particular endothelin receptors, are targets for therapeutic intervention in human diseases. Endothelin receptor antagonists have reached clinical use for treating pulmonary arterial hypertension, and are under clinical investigation for several other diseases, such as cancer, vasospasm or fibrogenic diseases. We review the molecules that have been evaluated in the main clinical trials, from the point of view of receptor selectivity and of their chemical characteristics which were important for efficacy in pulmonary hypertension. We will also discuss future use of antagonists to endothelin receptor(s) in several human diseases and what should be the necessary properties of the future molecules for efficacy in diseases where the presently tested molecules displayed suboptimal efficacy.

ARE PPARS NOVEL THERAPEUTIC TARGETS TO IMPROVE MELANOMA TREATMENT ?

Cutaneous melanoma is an aggressive malignant tumor of melanocytes, the pigment- producing cells of the epidermis, with a high incidence in developed countries. Despite some major clinical breakthroughs in the last few years, efficient therapies for metastatic melanoma, which portends a very bad prognosis, are still lacking. Among the potential therapeutic targets that have been attracting at-tention in melanoma are the peroxisome proliferator-activated receptors (PPARs). These members - a, ß and 7 - of the nuclear hormone receptor family, which are ligand-gated transcription factors endowed with a multitude of functions besides metabolism homeostasis, have displayed promising antitumor properties in a wide range of cancer cells, including melanoma. However, our knowledge of PPARs' functions in this skin cancer is far from complete, making the usefulness of any of the a, ß or 7 isotype as a therapeutic target uncertain. In this work, we showed that all three PPAR isotypes are expressed in normal melanocytes, in most melanoma cell lines and in primary and metastatic melanomas, and that PPAR/3 and 7 display transcriptional activity in normal melanocytes and melanoma cells. We also showed that the PPAR7 agonist rosiglitazone had anti-melanoma properties largely independent of PPAR7 expression, which was widely varying across the different cell lines and melanoma biopsies we evaluated and was not correlated with cell line stage. Consistent with the general view of PPAR7 as a tumor suppressor gene, we found that, in human samples, PPAR7 was less expressed in melanoma than in normal skin. Transcriptornic profiling of metastatic melanoma cells in which PPAR7 was pharmacologically modulated revealed an association with epithelial-to-mesenchymal transition, though the functional relevance of this finding remains to be determined. Collectively, our results suggests that PPAR7 activity in melanoma is highly complex and that a straightforward picture of PPAR7's role in this skin cancer is difficult to draw. In this study, we also provided compelling evidence that thioredoxin interacting protein (TXNIP) is, in melanoma, a bona fide PPAR7 target gene, the expression of which is repressed by PPAR7 activation. Although TXNIP is mostly known as an inhibitor of the major antioxidant thioredoxin, it has demonstrated a range of biological functions and is generally considered as a tumor suppressor gene. Consistently, we found that TXNIP expression is associated with growth arrest of melanoma cells in vitro and that forced expression of TXNIP strongly impairs cell proliferation. Interestingly, we also discovered that TXNIP favors melanoma cell migration while it diminishes their adhesion. Finally, we provided several lines of evidence that TXNIP may regulate these processes at the transcriptional level as well as by direct protein-protein interactions in the plasma membrane. Altogether, our findings suggest that the PPAR7 target TXNIP may be a double-edged sword in melanoma, hindering tumor growth but promoting invasion and dissemination. Experiments to evaluate the net biological outcome of TXNIP modulation in vivo are ongoing. -- Le mélanome cutané est une tumeur maligne agressive des mélanocytes, cellules de l'épiderme qui produisent la mélanine. Ce cancer présente un taux d'incidence élevé dans les pays développés et est grevé d'un pronostic très sombre une fois qu'il a disséminé. Malgré les importants progrès réalisés ces dernières années, aucune thérapie lie s'est encore montrée véritablement efficace contre le mélanome métastatique. Parmi les cibles thérapeutiques potentielles, nombre de groupes de recherche se sont penchés sur les peroxisome proliferator-activated receptors (PPARs). Ces récepteurs - a, ß et 7 - font partie de la famille des récepteurs nucléaires aux hormones, des facteurs de transcription activés par des ligands et dotés d'une multitude de fonctions en sus de la régulation du métabolisme. Ces protéines ont démontré des propriétés anti-tumorales prometteuses dans une large gamme de cellules cancéreuses, y compris le mélanome. Cependant, nous connaissons encore très mal les fonctions des PPARs dans ce cancer de la peau, rendant l'utilité thérapeutique de l'un des isotypes a, ß ou 7 incertaine. Dans ce travail, nous avons montré que les trois isotypes sont exprimés dans les mélanocytes normaux, dans la plupart des lignées de mélanome ainsi que dans des mélanomes primaires et métastatiques; nous avons aussi montré que PPAR/3 et 7 sont actifs sur le plan transcriptionnel dans les mélanocytes normaux et les cellules de mélanome. La rosiglitazone, un agoniste de PPAR7, a démontré des propriétés anti-mélanome essentiellement indépendantes de l'expression de PPAR7, qui semble très variable dans les lignées et les biopsies que nous avons évaluées; de plus, l'expression de PPAR7 n'est pas corrélée avec le stade de la lignée. En accord avec la vision communément admise de PPAR7 comme étant un gène suppresseur de tumeur, nous avons observé dans des échantillons humains que PPAR7 est moins exprimé dans les mélanomes que dans la peau normale. Une étude transcrip- tomique de cellules de mélanome métastatique a révélé que la modulation phar-macologique de PPAR7 est associée avec la transition épithélio-mésenchymateuse, même si la pertinence fonctionnelle de cette trouvaille reste à déterminer. Collec-tivement, ces résultats suggèrent que l'activité de PPAR/y dans le mélanome est hautement complexe et qu'une image claire du rôle de PPAR7 dans ce cancer est difficile à dessiner. Dans cette étude, nous avons également fourni de solides preuves que la thiore-doxin interacting protein (TXNIP) est, dans le mélanome, un gène cible bona fide de PPAR7 dont l'expression est réprimée par l'activation de PPAR7. Bien que TXNIP soit surtout connu comme un inhibiteur de la thiorédoxine -un anti-oxydant majeur - cette protéine a démontré une large gamme de fonctions biologiques et est généralement considérée comme un gène suppresseur de tumeur. En accord avec cette conception, nous avons trouvé que l'expression de TXNIP est associée avec l'arrêt de croissance des cellules de mélanome in vitro et que l'expression forcée de TXNIP freine considérablement la prolifération cellulaire. Nous avons aussi découvert que TXNIP favorise la migration des cellules de mélanome alors qu'elle diminue leur adhésion. Enfin, nous avons obtenu plusieurs preuves que TXNIP pourrait réguler ces processus tant au niveau transcriptionnel que par des interactions protéine-protéine au sein de la membrane plasmique. En conclusion, nos résultats suggèrent que la cible de PPAR7 TXNIP pourrait être une épée à double tranchant dans le mélanome, freinant la croissance tumorale mais favorisant l'invasion et la dissémination. Des expériences permettant d'évaluer l'effet biologique net de la modulation de TXNIP in vivo sont en cours.

Cancer du sein : la pathologie, pierre angulaire de la décision therapeutique [Breast cancer: pathology, the cornerstone of therapeutic decision]

Tailoring adjuvant therapy in breast cancer patients relies on prognostic and predictive factors, most of which are currently established by histopathological analysis of tumors. The quality of the assessment of the former (i.e.: tumor size, lymph node status, tumor grade, HER2 status, and lymphovascular invasion) and the latter (estrogen and progesteron receptors expression, HER2 overexpression or amplification) is an essential prerequisite for an optimal therapeutic decision. If the prognostic and predictive values of multigenes signatures are confirmed by on-going clinical studies, this approach could enter the clinical practice in the coming years and result in improved accuracy of adjuvant therapies in breast cancer patients. This approach might especially allow avoiding overtreatment in patients at low risk of recurrence.

Red meat and cancer risk in a network of case-control studies focusing on cooking practices.

BACKGROUND: Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. METHODS: We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. RESULTS: Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.

State of Iowa Department of Administrative Services Human Resource Enterprise: Review of State Hiring Practices, April 30, 2007

The State of Iowa and the Hiring Practices Working Group commissioned this review of the State’s hiring practices in response to recent concerns about these practices involving racial discrimination claims against the Departments of Human Services, Transportation, and Iowa Workforce Development. The State of Iowa should be commended for undertaking this review. The State has a longstanding Affirmative Action Program and commitment to diversity – they instituted their Affirmative Action Program in 1973, and continue their commitment to its success by making the changes necessary to ensure the program is viable and sustainable. Iowa Department of Administrative Services In July 2003, the State created the Iowa Department of Administrative Services (DAS) as a way to manage and coordinate the major resources of state government. DAS provides human resource services through an entrepreneurial management model. Entrepreneurial management is a customer-focused approach to delivering services. The customer departments have input about what services and products they want from DAS and in turn DAS is funded by the customer departments through purchases of DAS services and products. DAS looks to offer new and additional services (for example recruitment support and coordination) to various customers on a fee-for-service basis. A customer council is charged with approving the DAS business plan, establishing the rate for services, and reviewing service delivery and complaints. Under this entrepreneurial model, human resource services are provided by DAS-HRE (Human Resources Enterprise) central staff, 12 DAS-HRE Personnel Officers located at the customer departments, and customer agency staff. The majority of the recruitment and hiring functions are done by the customer (hiring) departments and their staff. Applications for employment are submitted using the BrassRing system with applicants being qualified by DAS-HRE employees. Since the creation of Human Resources Enterprise, DAS-HRE has strived to provide human resource tools to the departments. The Screening Manual and the Supervisor’s Manual are just two examples of the resources created for the hiring departments. They also provide Supervisor Training for newly appointed supervisors. Larger departments have dedicated staff assigned to human resource activities. The staff at the departmental level may or may not have a human resources background. Iowa Population and Workforce The 2000 U.S. Census indicated that Iowa’s population was 2,926,324. According to this census, 92.6 percent of Iowa’s population identified their race as white (alone). The nonwhite alone or minority population (including Black or African American, Asian, Native Hawaiian or Pacific Islander, Hispanic or Latino, American Indian or Alaska Native, two or more races, or some other race) was 7.4 percent.

Epithelial to mesenchymal transition in the pathogenesis of uterine malignant mixed Müllerian tumours: the role of ubiquitin proteasome system and therapeutic opportunities.

Malignant mixed Müllerian tumours (malignant mixed mesodermal tumours, MMMT) of the uterus are metaplastic carcinomas with a sarcomatous component and thus they are also called carcinosarcomas. It has now been accepted that the sarcomatous component is derived from epithelial elements that have undergone metaplasia. The process that produces this metaplasia is epithelial to mesenchymal transition (EMT), which has recently been described as a neoplasia-associated programme shared with embryonic development and enabling neoplastic cells to move and metastasise. The ubiquitin proteasome system (UPS) regulates the turnover and functions of hundreds of cellular proteins. It plays important roles in EMT by being involved in the regulation of several pathways participating in the execution of this metastasis-associated programme. In this review the specifi c role of UPS in EMT of MMMT is discussed and therapeutic opportunities from UPS manipulations are proposed.

Patients with AIDS-defining cancers are not universally screened for HIV: a 10-year retrospective analysis of HIV-testing practices in a Swiss university hospital.

OBJECTIVES: Kaposi's sarcoma (KS), invasive cervical carcinoma (ICC) and non-Hodgkin lymphoma (NHL) have been listed as AIDS-defining cancers (ADCs) by the Centers for Disease Control and Prevention since 1993. Despite this, HIV screening is not universally mentioned in ADC treatment guidelines. We examined screening practices at a tertiary centre serving a population where HIV seroprevalence is 0.4%. METHODS: Patients with KS, ICC, NHL and Hodgkin lymphoma (HL), treated at Lausanne University Hospital between January 2002 and July 2012, were studied retrospectively. HIV testing was considered part of the oncology work-up if performed between 90 days before and 90 days after the cancer diagnosis date. RESULTS: A total of 880 patients were examined: 10 with KS, 58 with ICC, 672 with NHL and 140 with HL. HIV testing rates were 100, 11, 60 and 59%, and HIV seroprevalence was 60, 1.7, 3.4 and 5%, respectively. Thirty-seven patients (4.2%) were HIV-positive, of whom eight (22%) were diagnosed at oncology work-up. All newly diagnosed patients had CD4 counts < 200 cells/μL and six (75%) had presented to a physician 12-236 weeks previously with conditions warranting HIV testing. CONCLUSIONS: In our institution, only patients with KS were universally screened. Screening rates for other cancers ranged from 11 to 60%. HIV seroprevalence was at least fourfold higher than the population average. As HIV-positive status impacts on cancer patient medical management, HIV screening should be included in oncology guidelines. Further, we recommend that opt-out screening should be adopted in all patients with ADCs and HL.

Therapeutic Drug Monitoring (TDM) of Imatinib: Effectiveness of Bayesian dose adjustment for CML patients enrolled in the Imatinib Concentration Monitoring (I-COME) study

Introduction: As imatinib pharmacokinetics are highly variable, plasma levels differ largely between patients under the same dosage. Retrospective studies in chronic myeloid leukemia (CML) patients showed significant correlations between low levels and suboptimal response, as well as between high levels and poor tolerability. Monitoring of trough plasma levels, targeting 1000 μg/L and above, is thus increasingly advised. Our study was launched to assess prospectively the clinical usefulness of systematic imatinib TDM in CML patients. This preliminary analysis addresses the appropriateness of the dosage adjustment approach applied in this study, which targets the recommended trough level and allows an interval of 4-24 h after last drug intake for blood sampling. Methods: Blood samples from the first 15 patients undergoing 1st TDM were obtained 1.5-25 h after last dose. Imatinib plasma levels were measured by LC-MS/MS and the concentrations were extrapolated to trough based on a Bayesian approach using a population pharmacokinetic model. Trough levels were predicted to differ significantly from the target in 12 patients (10 <750 μg/L; 2 >1500 μg/L along with poor tolerance) and individual dose adjustments were proposed. 8 patients underwent a 2nd TDM cycle. Trough levels of 1st and 2nd TDM were compared, the sample drawn 1.5 h after last dose (during distribution phase) was excluded from the analysis. Results: Individual dose adjustments were applied in 6 patients. Observed concentrations extrapolated to trough ranged from 360 to 1832 μg/L (median 725; mean 810, CV 52%) on 1st TDM and from 720 to 1187 μg/L (median 950; mean 940, CV 18%) on 2nd TDM cycle. Conclusions: These preliminary results suggest that TDM of imatinib using a Bayesian interpretation is able to target the recommended trough level of 1000 μg/L and to reduce the considerable differences in trough level exposure between patients (with CV decreasing from 52% to 18%). While this may simplify blood collection in daily practice, as samples do not have to be drawn exactly at trough, the largest possible interval to last drug intake yet remains preferable to avoid sampling during distribution phase leading to biased extrapolation. This encourages the evaluation of the clinical benefit of a routine TDM intervention in CML patients, which the randomized Swiss I-COME trial aims to.

Dealing with clients' diversity in test situations: Client categorisations in psychologists' accounts of their practices

Reducing a test administration to standardised procedures reflects the test designers' standpoint. However, from the practitioners' standpoint, each client is unique. How do psychologists deal with both standardised test administration and clients' diversity? To answer this question, we interviewed 17 psychologists working in three public services for children and adolescents about their assessment practices. We analysed the numerous "client categorisations" they produced in their accounts. We found that they had shared perceptions about their clients' diversity, and reported various non-standard practices that complemented standardised test administration, but also differed from them or were even forbidden. They seem to experience a dilemma between: (a) prescribed and situated practices; (b) scientific and situated reliability; (c) commutative and distributive justice. For practitioners, dealing with clients' diversity this is a practical problem, halfway between a problem-solving task and a moral dilemma.

Automated analysis of background EEG and reactivity during therapeutic hypothermia in comatose patients after cardiac arrest.

Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between reviewers. Automated EEG analysis may help quantify the brain damage. Forty-six comatose patients in therapeutic hypothermia, after cardiac arrest, were included in the study. EEG background was quantified with burst-suppression ratio (BSR) and approximate entropy, both used to monitor anesthesia. Reactivity was detected through change in the power spectrum of signal before and after stimulation. Automatic results obtained almost perfect agreement (discontinuity) to substantial agreement (background reactivity) with a visual score from EEG-certified neurologists. Burst-suppression ratio was more suited to distinguish continuous EEG background from burst-suppression than approximate entropy in this specific population. Automatic EEG background and reactivity measures were significantly related to good and poor outcome. We conclude that quantitative EEG measurements can provide promising information regarding current state of the patient and clinical outcome, but further work is needed before routine application in a clinical setting.