French Swiss physicians' attitude toward palliative sedation: Influence of prognosis and type of suffering.

OBJECTIVE: Palliative sedation is a last resort medical act aimed at relieving intolerable suffering induced by intractable symptoms in patients at the end-of-life. This act is generally accepted as being medically indicated under certain circumstances. A controversy remains in the literature as to its ethical validity. There is a certain vagueness in the literature regarding the legitimacy of palliative sedation in cases of non-physical refractory symptoms, especially "existential suffering." This pilot study aims to measure the influence of two independent variables (short/long prognosis and physical/existential suffering) on the physicians' attitudes toward palliative sedation (dependent variable). METHODS: We used a 2 × 2 experimental design as described by Blondeau et al. Four clinical vignettes were developed (vignette 1: short prognosis/existential suffering; vignette 2: long prognosis/existential suffering; vignette 3: short prognosis/physical suffering; vignette 4: long prognosis/physical suffering). Each vignette presented a terminally ill patient with a summary description of his physical and psychological condition, medication, and family situation. The respondents' attitude towards sedation was assessed with a six-point Likert scale. A total of 240 vignettes were sent to selected Swiss physicians. RESULTS: 74 vignettes were completed (36%). The means scores for attitudes were 2.62 ± 2.06 (v1), 1.88 ± 1.54 (v2), 4.54 ± 1.67 (v3), and 4.75 ± 1.71 (v4). General linear model analyses indicated that only the type of suffering had a significant impact on the attitude towards sedation (F = 33.92, df = 1, p = 0.000). Significance of the results: The French Swiss physicians' attitude toward palliative sedation is more favorable in case of physical suffering than in existential suffering. These results are in line with those found in the study of Blondeau et al. with Canadian physicians and will be discussed in light of the arguments given by physicians to explain their decisions.

Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.

PURPOSE: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol. EXPERIMENTAL DESIGN: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months. RESULTS: Eight dose levels (40-8,000 μg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 μg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 μg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 μg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days. CONCLUSION: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned.

Developing an Effective Construction Training Program for Hispanic and American Supervisors and Craft Workers, 2007

Hispanics are a large and growing part of the United States workforce. Projections of the U.S. Census Bureau (2001) state that, by the year 2050, Hispanics will account for 25% of the population. For the Midwest in particular, the Hispanic population is expected to increase 35% by the year 2025. The construction industry is expected to experience a greater percentage increase of its Hispanic population, due to the labor-intensive nature of the industry. This study addresses the expected increase of Hispanic workers in the construction industry by testing the best approaches for delivering training to construction crews with Hispanic workers as well as American supervisors and laborers in the state of Iowa. The research methodology consisted of assessing the effects on communication, safety, work environment, and productivity as a result of the integration training. Results show that integration on-site training decreases workers’ desire to move and increases quality of work and productivity. Most importantly, experimental design was used to show the increasing levels of direct construction communication due to the Toolbox Integration Course for Hispanic Workers and American Supervisors (TICHA) designed as part of this project. This study recommends the creation of a quasi-governmental or association program that can offer continuous research and training that can benefit the construction industry as well as society as a whole. The industry involvement in this process is crucial for contractors. Not only do contractors benefit from reduced insurance premiums when workers act safely, but workers with better communication skills are more productive.

Polymers as carriers for rhizobial inoculant formulations

The aim of this work was to evaluate the efficiency of carboxymethyl cellulose (CMC) and starch blends as carrier materials of rhizobial inoculants regarding their capacity to maintain viable cells and promote cowpea (Vigna unguiculata) nodulation. The experimental design adopted was completely randomized, with three replicates. Forty different compositions of carboxymethyl cellulose (CMC) with starch, compatibilized or not with different proportions of MgO or ZnO, were evaluated regarding their ability of maintaining rhizobial viable cells during the storage period of one month at room temperature, in an initial screening. Thereafter, selected inoculant carrier blends were evaluated regarding their ability to maintain viable rhizobial cells for a period of 165 days, and their performance as inoculant carriers was compared to a peat-based inoculant carrier under greenhouse conditions. Rhizobial cells were better maintained in blends containing 50-60% CMC. Compatibilizing agents did not increase survival of rhizobial cells for 30 days of storage. The cowpea nodulation of polymer blends was statistically the same of peat-based inoculants. CMC/starch polymer blends are efficient carriers to rhizobial inoculants for up to 165 days of storage, when compatibilized with MgO (1%).

Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.

Raman analysis of multilayer automotive paints in forensic science: measurement variability and depth profile?

The aim of this work is to study the influence of several analytical parameters on the variability of Raman spectra of paint samples. In the present study, microtome thin section and direct (no preparation) analysis are considered as sample preparation. In order to evaluate their influence on the measures, an experimental design such as 'fractional full factorial' with seven factors (including the sampling process) is applied, for a total of 32 experiments representing 160 measures. Once the influence of sample preparation highlighted, a depth profile of a paint sample is carried out by changing the focusing plane in order to measure the colored layer under a clearcoat. This is undertaken in order to avoid sample preparation such a microtome sectioning. Finally, chemometric treatments such as principal component analysis are applied to the resulting spectra. The findings of this study indicate the importance of sample preparation, or more specifically, the surface roughness, on the variability of the measurements on a same sample. Moreover, the depth profile experiment highlights the influence of the refractive index of the upper layer (clearcoat) when measuring through a transparent layer.

Adaptation of anthurium cultivars as cut flowers in a subtropical area

The objective of this work was to evaluate the adaptation of anthurium (Anthurium andraeanum) cultivars as cut flowers in a subtropical area, located in north of Paraná State, Brazil. The Apalai, Ianomami, Kinã, nK 102, Parakanã, Rubi, and Terena cultivars were cultivated in a nursery under 80% shade. The number of leaves and inflorescences, floral stem length, length and width of inflorescences, and spadix length were evaluated. The experimental design was in completely randomized blocks, with six replicates and five plants per plot. During the 18 months evaluated, 'Parakanã' produced 11 inflorescences per plant, whereas the other cultivars produced seven to nine inflorescences per plant. The number of leaves produced per plant was: 'Ianomami', 25; 'Parakanã', 20; 'Apalai' and 'Terena', 15; 'Kinã' and 'Rubi', 11; and 'nK 102', 9. The Apalai, nK 102, Parakanã, and Rubi cultivars are the most recommended as cut flowers; the Ianomami cultivar is not recommended as a cut flower in this region.

Cover plants with potential use for crop-livestock integrated systems in the Cerrado region

The objective of this work was to evaluate the effects of lignin, hemicellulose, and cellulose concentrations in the decomposition process of cover plant residues with potential use in no-tillage with corn, for crop-livestock integrated system, in the Cerrado region. The experiment was carried out at Embrapa Cerrados, in Planaltina, DF, Brazil in a split plot experimental design. The plots were represented by the plant species and the subplots by harvesting times, with three replicates. The cover plants Urochloa ruziziensis, Canavalia brasiliensis, Cajanus cajan, Pennisetum glaucum, Mucuna aterrima, Raphanus sativus, Sorghum bicolor were evaluated together with spontaneous plants in the fallow. Cover plants with lower lignin concentrations and, consequently, higher residue decomposition such as C. brasiliensis and U. ruziziensis promoted higher corn yield. High concentrations of lignin inhibit plant residue decomposition and this is favorable for the soil cover. Lower concentrations of lignin result in accelerated plant decomposition, more efficient nutrient cycling, and higher corn yield.

Improvement of productivity and polysaccharide-protein complex in Agaricus blazei

The objective of this work was to assess the productivity and polysaccharide-protein complex content of Agaricus blazei on rice straw medium, in comparison to conventional sawdust, using four casing soils. The A. blazei strain used was BCRC36814T, purchased from the Food Industry Research and Development Institute, Hsin-Chu, Taiwan. The two media were evaluated as to A. blazei productivity, harvesting time, and production costs. The experimental design used was a randomized complete block, with four replicates. Three local casing soils - Typic Paleudult (CCe), Typic Udorthent (Tq) and Oxyaquic Paleudult (TSp) - were compared to imported peat soil (PS, Saprists, Histosols), used as the control. The productivity of A. blazei using Tq and TSp soil was significantly higher. The TSp casing treatment resulted in earlier harvest by at least 14 to 27 days, when compared to the other treatments. The polysaccharide content in CCe (13.2%) and Tq soils (13.2%) did not differ significantly from the PS (13.4%) and TSp (10.6%) treatments. Local casing soils decreased the production costs of A. blazei cultivation. Composted rice straw can substitute sawdust as the culture medium for A. blazei production with increased yield.

Cover crops and herbicide timing management on soybean yield under no-tillage system

The objective of this work was to evaluate the effect of cover crops and timing of pre-emergence herbicide applications on soybean yield under no-tillage system. The experiment consisted of four cover crops (Panicum maximum, Urochloa ruziziensis, U. brizantha, and pearl millet) and fallow, in addition to four herbicide timings (30, 20, 10, and 0 days before soybean sowing), under no-tillage system (NTS), and of two control treatments under conventional tillage system (CTS). The experimental design was a completely randomized block, in a split-plot arrangement, with three replicates. Soybean under fallow, P. maximum, U. ruziziensis, U. brizantha, and pearl millet in the NTS and soybean under U. brizantha in the CTS did not differ significantly regarding yield. Soybean under fallow in the CTS significantly reduced yield when compared to the other treatments. The amount of straw on soil surface did not significantly affect soybean yield. Chemical management of P. maximum and U. brizantha near the soybean sowing date causes significant damage in soybean yield. However, herbicide timing in fallow, U. ruziziensis, and pearl millet does not affect soybean yield.

Grazing intensities and poultry litter fertilization levels on corn and black oat yield

The objective of this work was to assess the effect of poultry litter fertilization levels on corn and black oat yield using different grazing intensities, poultry litter levels (mixture of manure and bedding material) and a chemical fertilization level. The experimental design was a randomized complete block in a split-plot arrangement with four replicates. Black oat + ryegrass grazing intensities, characterized by different pasture sward management, with animal entrance at 25, 30 and 35-cm heights and exit at 5.0, 10 and 15-cm heights, were established at the main plots. After the grazing period, corn was grown at the subplots with four levels of poultry litter (0, 4,953, 9,907 and 14,860 kg ha-1), aiming to supply 0, 100, 200 and 300 kg ha-1 of nitrogen, and a treatment with chemical fertilizer, according to soil analysis. Grazing intensities had no effect on corn yield. Corn yield was 7,493, 8,458, 9,188, 10,247 and 11,028 kg ha-1, respectively, for the treatments without and with 4,953, 9,907 and 14,860 kg ha-1 of poultry litter, and the treatment with chemical fertilization. Poultry litter levels have a residual effect on the production of black oat grown in succession to corn.

Foraging behavior and ruminal fermentation of dairy cows grazing ryegrass pasture alone or with white clover

The objective of this work was to evaluate the influence of pasture composition and regrowth age on the relationship between feeding behavior and ruminal fermentation in dairy cows grazing perennial ryegrass with or without white clover. The experiment was carried out in a 2x2 factorial arrangement, with two sward types and two ages of regrowth. Swards of perennial ryegrass sown alone (PRG) and of perennial ryegrass mixed with white clover (GC) were evaluated. Twelve late-lactation Holstein cows, fistulated at the rumen, were distributed in a 4x4 latin square experimental design with four 12-day periods. Daily distribution of grazing was similar in the PRG and the GC swards, but the concentration of rumen volatile fatty acids (VFA) was higher and the proportion of propionate was lower on mixed swards during the day. Daily distribution of grazing was similar in pastures of different ages. However, in the oldest swards, rumen fluid pH increased and VFA concentration decreased after evening milking. Time spent grazing does not influence ruminal fermentation, which depends on the changes that occur as different sward layers are grazed.

Maintenance requirement and deposition efficiency of lysine in pigs

The objective of this work was to determine the maintenance requirement and the deposition efficiency of lysine in growing pigs. It was used the incomplete changeover experimental design, with replicates over time. Twelve castrated pigs with average body weight (BW) of 52±2 kg were kept in metabolism crates with a controlled temperature of 22ºC. The diets were formulated to supply 30, 50, 60, and 70% of the expected requirements of standardized lysine, and provided at 2.6 times the energy requirements for maintenance. The trial lasted 24 days and was divided into two periods of 12 days: seven days for animal adaptation to the diet and five days for sample collection. The increasing content of lysine in the diet did not affect dry matter intake of the pigs. The amount of nitrogen excreted was 47% of the nitrogen intake, of which 35% was excreted through feces and 65% through urine. The estimated endogenous losses of lysine were 36.4 mg kg-1 BW0.75. The maintenance requirement of lysine for pigs weighing around 50 kg is 40.4 mg kg-1 BW0.75, and the deposition efficiency of lysine is 90%.

Popping expansion and yield responses of popcorn cultivars under different row spacings and plant populations

The objective of this work was to evaluate the agronomic traits and the popping expansion index of three Brazilian popcorn cultivars under different row spacings and plant populations. The trials were performed during two crop seasons, under field conditions. The experimental design used was a randomized complete block, in a split-split plot, with 27 treatments and four replicates. Treatments were represented in a triple factorial arrangement: three row spacings (0.40, 0.60, and 0.80 m), three plant populations (40,000, 60,000, and 80,000 plants per hectare), and three popcorn cultivars (IAC-TC 01, IAC 12, and Zelia). The increase in plant population causes a reduction in the number of grains per ear, lower prolificacy, and grain weight loss. Cultivar grain yield is affected by row spacing and popcorn plant population. Cultivar IAC 12 shows highest grain yield under row spacings of 0.40 and 0.60 m and plant population between 60,000 and 80,000 plants per hectare. The popping expansion index is not affected by row spacing or plant population.

Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient with BRAFV600E-Mutated Cutaneous Melanoma Successfully Rechallenged after Progression.

PURPOSE: To investigate the mechanism(s) of resistance to the RAF-inhibitor vemurafenib, we conducted a comprehensive analysis of the genetic alterations occurring in metastatic lesions from a patient with a BRAF(V600E)-mutant cutaneous melanoma who, after a first response, underwent subsequent rechallenge with this drug. EXPERIMENTAL DESIGN: We obtained blood and tissue samples from a patient diagnosed with a BRAF(V600E)-mutant cutaneous melanoma that was treated with vemurafenib and achieved a near-complete response. At progression, he received additional lines of chemo/immunotherapy and was successfully rechallenged with vemurafenib. Exome and RNA sequencing were conducted on a pretreatment tumor and two subcutaneous resistant metastases, one that was present at baseline and previously responded to vemurafenib (PV1) and one that occurred de novo after reintroduction of the drug (PV2). A culture established from PV1 was also analyzed. RESULTS: We identified two NRAS-activating somatic mutations, Q61R and Q61K, affecting two main subpopulations in the metastasis PV1 and a BRAF alternative splicing, involving exons 4-10, in the metastasis PV2. These alterations, known to confer resistance to RAF inhibitors, were tumor-specific, mutually exclusive, and were not detected in pretreatment tumor samples. In addition, the oncogenic PIK3CA(H1047R) mutation was detected in a subpopulation of PV1, but this mutation did not seem to play a major role in vemurafenib resistance in this metastasis. CONCLUSIONS: This work describes the coexistence within the same patient of different molecular mechanisms of resistance to vemurafenib affecting different metastatic sites. These findings have direct implications for the clinical management of BRAF-mutant melanoma. Clin Cancer Res; 19(20); 5749-57. ©2013 AACR.