Sampling strategies for tropical forest nutrient cycling studies: a case study in São Paulo, Brazil

The precise sampling of soil, biological or micro climatic attributes in tropical forests, which are characterized by a high diversity of species and complex spatial variability, is a difficult task. We found few basic studies to guide sampling procedures. The objective of this study was to define a sampling strategy and data analysis for some parameters frequently used in nutrient cycling studies, i. e., litter amount, total nutrient amounts in litter and its composition (Ca, Mg, Κ, Ν and P), and soil attributes at three depths (organic matter, Ρ content, cation exchange capacity and base saturation). A natural remnant forest in the West of São Paulo State (Brazil) was selected as study area and samples were collected in July, 1989. The total amount of litter and its total nutrient amounts had a high spatial independent variance. Conversely, the variance of litter composition was lower and the spatial dependency was peculiar to each nutrient. The sampling strategy for the estimation of litter amounts and the amount of nutrient in litter should be different than the sampling strategy for nutrient composition. For the estimation of litter amounts and the amount of nutrients in litter (related to quantity) a large number of randomly distributed determinations are needed. Otherwise, for the estimation of litter nutrient composition (related to quality) a smaller amount of spatially located samples should be analyzed. The determination of sampling for soil attributes differed according to the depth. Overall, surface samples (0-5 cm) showed high short distance spatial dependent variance, whereas, subsurface samples exhibited spatial dependency in longer distances. Short transects with sampling interval of 5-10 m are recommended for surface sampling. Subsurface samples must also be spatially located, but with transects or grids with longer distances between sampling points over the entire area. Composite soil samples would not provide a complete understanding of the relation between soil properties and surface dynamic processes or landscape aspects. Precise distribution of Ρ was difficult to estimate.

Access to a simulator is not enough: the benefits of virtual reality training based on peer-group-derived benchmarks--a randomized controlled trial.

BACKGROUND: Virtual reality (VR) simulators are widely used to familiarize surgical novices with laparoscopy, but VR training methods differ in efficacy. In the present trial, self-controlled basic VR training (SC-training) was tested against training based on peer-group-derived benchmarks (PGD-training). METHODS: First, novice laparoscopic residents were randomized into a SC group (n = 34), and a group using PGD-benchmarks (n = 34) for basic laparoscopic training. After completing basic training, both groups performed 60 VR laparoscopic cholecystectomies for performance analysis. Primary endpoints were simulator metrics; secondary endpoints were program adherence, trainee motivation, and training efficacy. RESULTS: Altogether, 66 residents completed basic training, and 3,837 of 3,960 (96.8 %) cholecystectomies were available for analysis. Course adherence was good, with only two dropouts, both in the SC-group. The PGD-group spent more time and repetitions in basic training until the benchmarks were reached and subsequently showed better performance in the readout cholecystectomies: Median time (gallbladder extraction) showed significant differences of 520 s (IQR 354-738 s) in SC-training versus 390 s (IQR 278-536 s) in the PGD-group (p < 0.001) and 215 s (IQR 175-276 s) in experts, respectively. Path length of the right instrument also showed significant differences, again with the PGD-training group being more efficient. CONCLUSIONS: Basic VR laparoscopic training based on PGD benchmarks with external assessment is superior to SC training, resulting in higher trainee motivation and better performance in simulated laparoscopic cholecystectomies. We recommend such a basic course based on PGD benchmarks before advancing to more elaborate VR training.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Which is the optimal sampling strategy for habitat suitability modelling

Designing an efficient sampling strategy is of crucial importance for habitat suitability modelling. This paper compares four such strategies, namely, 'random', 'regular', 'proportional-stratified' and 'equal -stratified'- to investigate (1) how they affect prediction accuracy and (2) how sensitive they are to sample size. In order to compare them, a virtual species approach (Ecol. Model. 145 (2001) 111) in a real landscape, based on reliable data, was chosen. The distribution of the virtual species was sampled 300 times using each of the four strategies in four sample sizes. The sampled data were then fed into a GLM to make two types of prediction: (1) habitat suitability and (2) presence/ absence. Comparing the predictions to the known distribution of the virtual species allows model accuracy to be assessed. Habitat suitability predictions were assessed by Pearson's correlation coefficient and presence/absence predictions by Cohen's K agreement coefficient. The results show the 'regular' and 'equal-stratified' sampling strategies to be the most accurate and most robust. We propose the following characteristics to improve sample design: (1) increase sample size, (2) prefer systematic to random sampling and (3) include environmental information in the design'

Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy--EORTC Infectious Diseases Group Trial XV.

PURPOSE This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer. PATIENTS AND METHODS Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference). Results Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms. CONCLUSION Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.

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.

Psychodynamic psychotherapy in newly diagnosed cancer patients: a randomized controlled trial

Background and aims: More than 30% of cancer patients develop a psychiatric disorder during the evolution of their disease. While evidence exists, that psychotherapy can improve psychological distress, questions, such as the prevalence of patients accepting psychotherapy, treatment indications and effectiveness of psychotherapeutic interventions in the oncology setting remain unanswered. The aims were: (1) To assess the prevalence of newly diagnosed cancer patients motivated to engage in psychotherapeutic interventions; (2) to identify those who benefit; and (3) to evaluate their effectiveness. Methods: Every new patient of the Oncology Service at the University Hospital Lausanne was informed of the possibility of benefitting from psychotherapeutic support. Patients who accepted were randomly assigned to individual psychotherapy or to a 4-month waiting list. Psychotherapies were formalized as psychodynamicoriented short interventions (1-4 sessions) or brief psychodynamic psychotherapies (16 sessions). Patients who refused psychotherapy were asked to participate in an observational group. Socio-demographic and medical data, anxiety, depression, alexithymia and quality of life (SCL- 90, HADS, TAS, EORTC) of all participants were evaluated at base line and at 1, 4, 8 and 12 -months Follow- Up. Results: So far 1047 patients have been approached, 20% were included in the study (intervention n=68, observation n=122), 32% were excluded, 22% could not be contacted and 26% refused to participate. At baseline, patients who accepted psychotherapeutic support showed higher depression and anxiety scores (HADS, SCL-90) compared to controls. 56% benefited from 4 sessions of psychological support, 44% engaged in 16 sessions of brief psychodynamic therapy. Conclusions: The preliminary results of this ongoing trial suggest that a minority of newly cancer patients accept psychotherapeutic intervention. These patients are more depressed than controls. Their motivation for short interventions and for brief psychotherapies is comparable.

10-year follow-up of a prospective randomized trial comparing bare-metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial

OBJECTIVES: This study was designed to compare the long-term clinical outcome of coronary artery bypass grafting (CABG) with intracoronary stenting of patients with isolated proximal left anterior descending coronary artery. BACKGROUND: Although numerous trials have compared coronary angioplasty with bypass surgery, none assessed the clinical evaluation in the long term. METHODS: We evaluated the 10-year clinical outcome in the SIMA (Stent versus Internal Mammary Artery grafting) trial. Patients were randomly assigned to stent implantation versus CABG. RESULTS: Of 123 randomized patients, 59 underwent CABG and 62 received a stent (2 patients were excluded). Follow-up after 10 years was obtained for 98% of the randomized patients. Twenty-six patients (42%) in the percutaneous coronary intervention group and 10 patients (17%) in the CABG group reached an end point (p < 0.001). This difference was due to a higher need for additional revascularization. The incidences of death and myocardial infarction were identical at 10%. Progression of the disease requiring additional revascularization was rare (5%) and was similar for the 2 groups. Stent thrombosis occurred in 2 patients (3%). Angina functional class showed no significant differences between the 2 groups. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective in relieving symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Stenting with bare-metal stents is associated with a higher need for repeat interventions. The long-term prognosis for these patients is excellent with either mode of revascularization.

Report on the Iowa Judicial Branch – County Clerks of District Courts, a part of the State of Iowa, for the year ended June 30, 2008

Report on the Iowa Judicial Branch – County Clerks of District Courts, a part of the State of Iowa, for the year ended June 30, 2008

Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial.

BACKGROUND: In alcohol withdrawal, fixed doses of benzodiazepine are generally recommended as a first-line pharmacologic approach. This study determines the benefits of an individualized treatment regimen on the quantity of benzodiazepine administered and the duration of its use during alcohol withdrawal treatment. METHODS: We conducted a prospective, randomized, double-blind, controlled trial including 117 consecutive patients with alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, entering an alcohol treatment program at both the Lausanne and Geneva university hospitals, Switzerland. Patients were randomized into 2 groups: (1) 56 were treated with oxazepam in response to the development of signs of alcohol withdrawal (symptom-triggered); and (2) 61 were treated with oxazepam every 6 hours with additional doses as needed (fixed-schedule). The administration of oxazepam in group 1 and additional oxazepam in group 2 was determined using a standardized measure of alcohol withdrawal. The main outcome measures were the total amount and duration of treatment with oxazepam, the incidence of complications, and the comfort level. RESULTS: A total of 22 patients (39%) in the symptom-triggered group were treated with oxazepam vs 100% in the fixed-schedule group (P<.001). The mean oxazepam dose administered in the symptom-triggered group was 37.5 mg compared with 231.4 mg in the fixed-schedule group (P<.001). The mean duration of oxazepam treatment was 20.0 hours in the symptom-triggered group vs 62.7 hours in the fixed-schedule group (P<.001). Withdrawal complications were limited to a single episode of seizures in the symptom-triggered group. There were no differences in the measures of comfort between the 2 groups. CONCLUSIONS: Symptom-triggered benzodiazepine treatment for alcohol withdrawal is safe, comfortable, and associated with a decrease in the quantity of medication and duration of treatment.

Ranibizumab versus Bevacizumab for Neovascular Age-related Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial.

OBJECTIVE: To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD). DESIGN: Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters. PARTICIPANTS: Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA). METHODS: Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up. MAIN OUTCOME MEASURES: Mean change in visual acuity at 1 year. RESULTS: Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval [CI], -1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups. CONCLUSIONS: Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Sampling and TDR probe insertion in the determination of the volumetric soil water content

Volumetric soil water content (theta) can be evaluated in the field by direct or indirect methods. Among the direct, the gravimetric method is regarded as highly reliable and thus often preferred. Its main disadvantages are that sampling and laboratory procedures are labor intensive, and that the method is destructive, which makes resampling of a same point impossible. Recently, the time domain reflectometry (TDR) technique has become a widely used indirect, non-destructive method to evaluate theta. In this study, evaluations of the apparent dielectric number of soils (epsilon) and samplings for the gravimetrical determination of the volumetric soil water content (thetaGrav) were carried out at four sites of a Xanthic Ferralsol in Manaus - Brazil. With the obtained epsilon values, theta was estimated using empirical equations (thetaTDR), and compared with thetaGrav derived from disturbed and undisturbed samples. The main objective of this study was the comparison of thetaTDR estimates of horizontally as well as vertically inserted probes with the thetaGrav values determined by disturbed and undisturbed samples. Results showed that thetaTDR estimates of vertically inserted probes and the average of horizontally measured layers were only slightly and insignificantly different. However, significant differences were found between the thetaTDR estimates of different equations and between disturbed and undisturbed samples in the thetaGrav determinations. The use of the theoretical Knight et al. model, which permits an evaluation of the soil volume assessed by TDR probes, is also discussed. It was concluded that the TDR technique, when properly calibrated, permits in situ, nondestructive measurements of q in Xanthic Ferralsols of similar accuracy as the gravimetric method.

The synthetic Plasmodium falciparum circumsporozoite peptide PfCS102 as a malaria vaccine candidate: a randomized controlled phase I trial.

BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102) in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg) and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity) was based on the frequency of adverse events (AE) and of abnormal biological safety tests; secondary-end point (immunogenicity) on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema). After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+) T cell responses. Responses were only marginally boosted after the 3(rd) vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential for protection. Two or three immunizations with a dose of 30 microg formulated with AS02A appeared the most appropriate choice for such studies. TRIAL REGISTRATION: Swissmedic.ch 2002 DR 1227.