Exploring the effectiveness of development research with a monitoring and learning approach

There is a growing demand for better understanding of the link between research, policy and practice in development. This article provides findings from a study that aimed to gain insights into how researchers engage with their non-academic partners. It draws on experiences from the National Centre of Competence in Research North-South programme, a development research network of Swiss, African, Asian and Latin American institutions. Conceptually, this study is concerned with research effectiveness as a means to identify knowledge useful for society. Research can be improved and adapted when monitoring the effects of interactions between researchers and non-academic partners. Therefore, a monitoring and learning approach was chosen. This study reveals researchers' strategies in engaging with non-academic partners and points to framing conditions considered decisive for soccessful interactions. It concludes that reserachrs need to systematically analyse the socio-political context in which they intervene. By providing insights from the ground and reflecting on them in the light of the latest theoretical concepts, this article contributes to the emerging literature founded on practice-based experience.

Inhibition of cytochrome P450 enzymes involved in ketamine metabolism by use of liver microsomes and specific cytochrome P450 enzymes from horses, dogs, and humans

To identify and characterize cytochrome P450 enzymes (CYPs) responsible for the metabolism of racemic ketamine in 3 mammalian species in vitro by use of chemical inhibitors and antibodies.

Hypercalcemia in the ED: prevalence, etiology, and outcome

The aim of the study was to describe the prevalence, demographic, and clinical characteristics and etiologies of hypercalcemia in emergency department patients.

Erosive tooth wear: diagnosis, risk factors and prevention

PURPOSE: To provide an overview on diagnosis, risk factors and prevention of erosive tooth wear, which is becoming an increasingly important factor when considering the long- term health of the dentition. RESULTS: Awareness of dental erosion by the public is still not widespread due to the cryptic nature of this slowly progressing condition. Smooth silky-glazed appearance with the absence of perikymata and intact enamel along the gingival margin, with cupping and grooving on occlusal surfaces are some typical signs of enamel erosion. In later stages, it is sometimes difficult to distinguish between the influences of erosion, attrition or abrasion during a clinical examination. Biological, behavioral and chemical factors all come into play, which over time, may either wear away the tooth surface, or potentially protect it. In order to assess the risk factors, patient should record their dietary intake for a distinct period of time. Based on these analyses, an individually tailored preventive program may be suggested to patients. It may comprise dietary advice, optimization of fluoride regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for non-destructive tooth brushing habits. The frequent use of fluoride gel and fluoride mouthrinse in addition to fluoride toothpaste offers the opportunity to minimize abrasion of tooth substance.

Multicentre study on peri- and postoperative central venous oxygen saturation in high-risk surgical patients

Introduction Low central venous oxygen saturation (ScvO2) has been associated with increased risk of postoperative complications in high-risk surgery. Whether this association is centre-specific or more generalisable is not known. The aim of this study was to assess the association between peri- and postoperative ScvO2 and outcome in high-risk surgical patients in a multicentre setting. Methods Three large European university hospitals (two in Finland, one in Switzerland) participated. In 60 patients with intra-abdominal surgery lasting more than 90 minutes, the presence of at least two of Shoemaker's criteria, and ASA (American Society of Anesthesiologists) class greater than 2, ScvO2 was determined preoperatively and at two hour intervals during the operation until 12 hours postoperatively. Hospital length of stay (LOS) mortality, and predefined postoperative complications were recorded. Results The age of the patients was 72 ± 10 years (mean ± standard deviation), and simplified acute physiology score (SAPS II) was 32 ± 12. Hospital LOS was 10.5 (8 to 14) days, and 28-day hospital mortality was 10.0%. Preoperative ScvO2 decreased from 77% ± 10% to 70% ± 11% (p < 0.001) immediately after surgery and remained unchanged 12 hours later. A total of 67 postoperative complications were recorded in 32 patients. After multivariate analysis, mean ScvO2 value (odds ratio [OR] 1.23 [95% confidence interval (CI) 1.01 to 1.50], p = 0.037), hospital LOS (OR 0.75 [95% CI 0.59 to 0.94], p = 0.012), and SAPS II (OR 0.90 [95% CI 0.82 to 0.99], p = 0.029) were independently associated with postoperative complications. The optimal value of mean ScvO2 to discriminate between patients who did or did not develop complications was 73% (sensitivity 72%, specificity 61%). Conclusion Low ScvO2 perioperatively is related to increased risk of postoperative complications in high-risk surgery. This warrants trials with goal-directed therapy using ScvO2 as a target in high-risk surgery patients.

Ventricular-arterial coupling in a rat model of reduced arterial compliance provoked by hypervitaminosis D and nicotine

The vitamin D(3) and nicotine (VDN) model is one of isolated systolic hypertension (ISH) in which arterial calcification raises arterial stiffness and vascular impedance. The effects of VDN treatment on arterial and cardiac hemodynamics have been investigated; however, a complete analysis of ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9), and a control group (n = 10) was included without the VDN. At week 8, invasive indexes of cardiac function were obtained using a conductance catheter. Simultaneously, aortic pressure and flow were measured to derive vascular impedance and characterize ventricular-vascular interaction. VDN caused significant increases in systolic (138 +/- 6 vs. 116 +/- 13 mmHg, P < 0.01) and pulse (42 +/- 10 vs. 26 +/- 4 mmHg, P < 0.01) pressures with respect to control. Total arterial compliance decreased (0.12 +/- 0.08 vs. 0.21 +/- 0.04 ml/mmHg in control, P < 0.05), and pulse wave velocity increased significantly (8.8 +/- 2.5 vs. 5.1 +/- 2.0 m/s in control, P < 0.05). The arterial elastance and end-systolic elastance rose significantly in the VDN group (P < 0.05). Wave reflection was augmented in the VDN group, as reflected by the increase in the wave reflection coefficient (0.63 +/- 0.06 vs. 0.52 +/- 0.05 in control, P < 0.05) and the amplitude of the reflected pressure wave (13.3 +/- 3.1 vs. 8.4 +/- 1.0 mmHg in control, P < 0.05). We studied ventricular-arterial coupling in a VDN-induced rat model of reduced arterial compliance. The VDN treatment led to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree.

Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome

BACKGROUND: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. METHODS: Long-term follow-up was evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. RESULTS: Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (andard deviation score in 6 patients) significantly increased (P < 0.05) at the end of follow-up in comparison to values at diagnosis. Nonpostural persistent proteinuria was present in 6 patients, and 4 patients had a glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s). CONCLUSION: These data show that some patients with biallelic mutations in the chloride channel gene CLCNKB tend to present with pathological proteinuria and impaired kidney function after a median follow-up of 14 years, and growth retardation is common and sometimes related to growth hormone deficiency in these patients.

Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis

In many human carcinomas, expression of the lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D) correlates with up-regulated lymphangiogenesis and regional lymph node metastasis. Here, we have used the Rip1Tag2 transgenic mouse model of pancreatic beta-cell carcinogenesis to investigate the functional role of VEGF-D in the induction of lymphangiogenesis and tumor progression. Expression of VEGF-D in beta cells of single-transgenic Rip1VEGF-D mice resulted in the formation of peri-insular lymphatic lacunae, often containing leukocyte accumulations and blood hemorrhages. When these mice were crossed to Rip1Tag2 mice, VEGF-D-expressing tumors also exhibited peritumoral lymphangiogenesis with lymphocyte accumulations and hemorrhages, and they frequently developed lymph node and lung metastases. Notably, tumor outgrowth and blood microvessel density were significantly reduced in VEGF-D-expressing tumors. Our results demonstrate that VEGF-D induces lymphangiogenesis, promotes metastasis to lymph nodes and lungs, and yet represses hemangiogenesis and tumor outgrowth. Because a comparable transgenic expression of vascular endothelial growth factor-C (VEGF-C) in Rip1Tag2 has been shown previously to provoke lymphangiogenesis and lymph node metastasis in the absence of any distant metastasis, leukocyte infiltration, or angiogenesis-suppressing effects, these results reveal further functional differences between VEGF-D and VEGF-C.

Drug-eluting or bare-metal stents for large coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: study protocol and design

BACKGROUND: Based on a subgroup analysis of 18-month BAsel Stent Kosten Effektivitäts Trial (BASKET) outcome data, we hypothesized that very late (> 12 months) stent thrombosis occurs predominantly after drug-eluting stent implantation in large native coronary vessel stenting. METHODS: To prove or refute this hypothesis, we set up an 11-center 4-country prospective trial of 2260 consecutive patients treated with > or = 3.0-mm stents only, randomized to receive Cypher (Johnson ; Johnson, Miami Lakes, FL), Vision (Abbott Vascular, Abbott Laboratories, IL), or Xience stents (Abbott Vascular). Only patients with left main or bypass graft disease, in-stent restenosis or stent thrombosis, in need of nonheart surgery, at increased bleeding risk, without compliance/consent are excluded. All patients are treated with dual antiplatelet therapy for 12 months. The primary end point will be cardiac death/nonfatal myocardial infarction after 24 months with further follow-up up to 5 years. RESULTS: By June 12, 229 patients (10% of the planned total) were included with a baseline risk similar to that of the same subgroup of BASKET (n = 588). CONCLUSIONS: This study will answer several important questions of contemporary stent use in patients with large native vessel stenting. The 2-year death/myocardial infarction-as well as target vessel revascularization-and bleeding rates in these patients with a first- versus second-generation drug-eluting stent should demonstrate the benefit or harm of these stents compared to cobalt-chromium bare-metal stents in this relevant, low-risk group of everyday patients. In addition, a comparison with similar BASKET patients will allow to estimate the impact of 12- versus 6-month dual antiplatelet therapy on these outcomes.

In vitro evaluation of differences in phase 1 metabolism of ketamine and other analgesics among humans, horses, and dogs

OBJECTIVE: To investigate cytochrome P450 (CYP) enzymes involved in metabolism of racemic and S-ketamine in various species and to evaluate metabolic interactions of other analgesics with ketamine. SAMPLE POPULATION: Human, equine, and canine liver microsomes. PROCEDURES: An analgesic was concurrently incubated with luminogenic substrates specific for CYP 3A4 or CYP 2C9 and liver microsomes. The luminescence signal was detected and compared with the signal for negative control samples. Ketamine and norketamine enantiomers were determined by use of capillary electrophoresis. RESULTS: A concentration-dependent decrease in luminescence signal was detected for ibuprofen and diclofenac in the assay for CYP 2C9 in human and equine liver microsomes but not in the assay for CYP 3A4 and methadone or xylazine in any of the species. Coincubation of methadone or xylazine with ketamine resulted in a decrease in norketamine formation in equine and canine liver microsomes but not in human liver microsomes. In all species, norketamine formation was not affected by ibuprofen, but diclofenac reduced norketamine formation in human liver microsomes. A higher rate of metabolism was detected for S-ketamine in equine liver microsomes, compared with the rate for the S-enantiomer in the racemic mixture when incubated with any of the analgesics investigated. CONCLUSIONS AND CLINICAL RELEVANCE: Enzymes of the CYP 3A4 family and orthologs of CYP 2C9 were involved in ketamine metabolism in horses, dogs, and humans. Methadone and xylazine inhibited in vitro metabolism of ketamine. Therefore, higher concentrations and diminished clearance of ketamine may cause adverse effects when administered concurrently with other analgesics.

Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy

BACKGROUND: Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. OBJECTIVES: To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia. AUTHORS' CONCLUSIONS: There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.

Expected and Unexpected Consequences of the Educational Expansion in Europe and the US. Theoretical approaches and empirical findings in comparative perspective

A main mechanism behind the change in European and North American societies in the second half of the 20th century is the educational expansion, i.e. the increase in educational opportunities and the higher demand for education. Whereas other abstract social processes like modernization have been widely theorized in social science literature, the educational expansion and its consequences in particular have not been well studied. Therefore the main aim of this compilation is to deal with the question of whether the demands of the educational reforms have been fulfilled and which other consequences the educational expansion has had. This book will focus on consequences of the educational expansion for individuals and their life courses as well as for the social structure and other societal areas such as culture and politics. Aspects that will be analysed in the light of educational expansion include participation in education, educational inequalities, labour market outcomes, educational returns, and gender differences as well as crime, life expectancy, and lifestyles. Countries analysed in the book include West European countries like Germany, France, Italy and Spain, East European countries (Hungary, Poland, and the Czech Republic) as well as the US.