Public views about editing genes in wildlife for conservation.

Developments in CRISPR-based gene-editing technologies have generated a growing number of proposals to edit genes in wildlife to meet conservation goals. As these proposals have attracted greater attention, controversies have emerged among scientists and stakeholder groups over potential consequences and ethical implications of gene editing. Responsible governance cannot occur without consulting broader publics, yet little effort has been made to systematically assess public understandings and beliefs in relation to this new area of applied genetic engineering. We analyzed data from a survey of U.S. adults (n = 1600), collected by YouGov, and that examined respondents' concerns about gene editing in animal and plant wildlife and how those concerns are shaped by cultural dispositions toward science and beliefs about the appropriateness of intervening in nature at the genetic level. On average, respondents perceived more risk than benefit in using these tools. Over 70% agreed that gene editing in wildlife could be "easily used for the wrong purposes." When evaluating the moral acceptability of gene editing in wildlife, respondents evaluated applications to improve survival in endangered wildlife as more morally acceptable than applications to decrease abundance in a population or eliminate a population. Belief in the authority of scientific knowledge was positively related to favorable views of the benefits, risks, and moral acceptability of editing genes in wildlife. The belief that editing genes in wildlife inappropriately intervenes in nature predicted relatively more concern about risks and moral acceptability and skepticism about benefits. Given high levels of concern and skepticism about gene editing in wildlife for conservation among the U.S. public, a take-it-slow approach to making decisions about when or whether to use these tools is advisable. Early opinions, including those uncovered in this study, are likely to be provisional. Thus, consulting the public should be an ongoing process.

Opinión Pública sobre la Edición de Genes en la Conservación de Fauna Resumen El desarrollo de tecnologías de edición de genes basada en CRISPR ha generado un número creciente de propuestas para editar los genes de especies silvestres y así lograr los objetivos de conservación. Conforme estas propuestas han atraído la atención, han surgido controversias entre los grupos de científicos y accionistas sobre las consecuencias potenciales y las implicaciones éticas de la edición de genes. La gobernanza responsable no puede ocurrir sin consultar a una audiencia más amplia, y aun así se han realizado muy pocos esfuerzos por evaluar sistemáticamente las creencias y el entendimiento público relacionados con esta nueva etapa de ingeniería genética aplicada. Analizamos los resultados de una encuesta en línea realizado por YouGov entre adultos de los Estados Unidos (n = 1,600), la cual examinaba las preocupaciones de los respondientes sobre la edición genética en animales y plantas y cómo estas preocupaciones están moldeadas por la disposición cultural hacia la ciencia y las creencias sobre lo correcto que es intervenir en la naturaleza a nivel genético. En promedio, los respondientes percibieron más un riesgo que un beneficio al usar estas herramientas. Más del 70% estuvo de acuerdo en que la edición genética de especies silvestres podría "usarse fácilmente para los propósitos equivocados". Cuando evaluamos la aceptación moral de la edición genética de la fauna, los respondientes calificaron a las aplicaciones para incrementar la supervivencia de las especies amenazadas como más aceptables moralmente que las aplicaciones para disminuir la abundancia de una población o eliminarla totalmente. La creencia en la autoridad del conocimiento científico estuvo relacionada positivamente con la opinión favorable sobre los beneficios, riesgos y la aceptación moral de la edición genética de especies silvestres. La creencia de que la edición genética de especies silvestres interviene inapropiadamente con la naturaleza predijo relativamente una mayor preocupación por los riesgos y la aceptación moral y mayor escepticismo sobre los beneficios de la edición genética. Debido a los altos niveles de preocupación y escepticismo sobre la edición genética de especies silvestres para la conservación mostrados por el público estadunidense, se recomienda utilizar una estrategia de hazlo-con-calma para decidir cuándo o si usar estas herramientas. Es probable que las primeras opiniones, incluyendo las descubiertas con este estudio, sean provisionales. Por lo tanto, consultar al público debe ser un proceso continuo.

Does thoracoscopic anterior release of rigid idiopathic scolioses associated with correction by posterior instrumentation result in better long-term frontal and sagittal balance?

INTRODUCTION: The aim of treatment of scolioses is to reduce deformities and restore balance in the spine. HYPOTHESES: In rigid forms of scoliosis, associating anterior release could provide greater frontal and/or sagittal plane correction and improve balance in the spine. PATIENTS AND METHODS: This study compared correction and long-term balance on two planes between two homogeneous groups of idiopathic rigid scolioses treated with and without thoracoscopic release. The study included rigid scolioses with less than 35% reducibility and a Cobb angle of more than 60°, who all underwent posterior correction using a rod rotation technique. There were 29 patients, 14 who underwent a one-step procedure (group A) and 15 a two-step procedure (group B), with the subgroups of kyphoscolioses and lordoscolioses determined in each group. Frontal balance, Cobb angle, thoracic kyphosis and the Jackson plumbline were measured on pre- and postoperative X-rays and at the final follow-up. RESULTS: The mean long-term final follow-up was 144 months for group A and 54 months for group B. Frontal plane correction was identical in groups A and B. Frontal balance was preserved in all cases at the final follow-up. Sagittal balance was not modified with or without anterior release. The thoracoscopic release step resulted in an additional correction of 15.5° (23%) of thoracic hyperkyphosis in patients with kyphoscoliosis (P=0.003). DISCUSSION: Thoracoscopy did not improve short term results in the Cobb angle or frontal or saggital balance. Nevertheless, enhanced correction of thoracic hyperkyphosis was obtained with this procedure. In this study, the association of thoracoscopic anterior release with posterior correction by rod rotation to treat rigid scolioses did not appear to improve results, except for the correction of thoracic hyperkyphosis.

[Correction of stiff thoracic idiopathic adult scoliosis. Prediction from the traction radiograph]. / Réduction des scolioses idiopathiques raides de l'adulte.

PURPOSE OF THE STUDY: The aim of this study was to determine the predictive value of the traction radiograph in adults with stiff curve (preoperative Cobb angle>60 degrees and reduction of less than 35% with traction) thoracic scoliosis. We wanted to compare this predictive value with that observed in reducible scoliosis. MATERIAL AND METHODS: A traction radiograph was obtained using a standard protocol with dynamometric control of the force applied. Patients with stiff scoliosis had 47 thoracic curves and 11 thoracolumbar curves (with primary anterior release for ten thoracic curves and eight thoracolumbar curves) and patients with reducible scoliosis had 56 thoracic curves. Cortre-Dubousset instrumentation was used for treatment in all patients. RESULTS: The postoperative Cobb angle for the stiff curves (without anterior release) was strongly correlated with the preoperative angle with traction (r=0.91; p<0.0001). The correlation between the postoperative Cobb angle and the preoperative Cobb angle without traction was less pronounced (r=0.86; p<0.0001). The traction radiographs were less predictive of the Cobb angle correction than the postoperative Cobb angle. The difference was 17.5+/-7 degrees , which corresponds to a supplementary gain in reduction after surgery. For the thoracic curves alone, the differences between the traction Cobb angle and the postoperative Cobb angle was 14.5 degrees for stiff curves and 6.5 degrees for reducible curves. Furthermore, the correlation between the Cobb angle with traction and the postoperative Cobb angle was stronger for stiff curve thoracic scoliosis (r=0.90) than reducible thoracic scoliosis (r=0.78). DISCUSSION AND CONCLUSION: The standard traction radiographs were highly predictive of postoperative reduction of stiff thoracic and thoracolumbar curves treated by segmental instrumentation. The postoperative result can thus be estimated with a margin of error of +/-7 degrees . For the stiff curves, the postoperative Cobb angle was 17.5 degrees on average less than predicted on the traction radiograph (on average 20% supplementary gain in reduction). This angle gain, which was greater for stiff than reducible curves, corresponds to the determining effect of release occurring with stiff curves. Finally, because of the stronger correlation between the traction Cobb angle and the postoperative Cobb angle for stiff curves, the predictive value of the traction radiograph is greater for stiff curves than for reducible curves. In conclusion, one of the contributions of the traction radiograph, which results from the predictability of the postoperative angle with a small margin of error, is to enable adequate prediction of the postoperative outcome for a given patient or a specific sub-group of patients, e.g. with or without anterior release.

[Study of the usefulness of pharmacist consultations for patients on antiretroviral regimens]. / Enquête sur la mise en place d'une consultation pharmaceutique pour les patients sous antirétroviraux.

OBJECTIVE: Highly active anti-retroviral therapies (HAART) in HIV treatment can result in complex treatment regimens. We surveyed HIV patients followed in the infectious disease department of Saint-Germain-en-Laye Hospital to assess the interest of offering patients a consultation with a pharmacist. METHODS: The 3-part questionnaire enabled us to assess the medical and pharmaceutical information given to the patient, adherence, and risk factors for poor observance. The questionnaire was distributed to all patients, regardless of whether they were receiving treatment. A simple adherence score was computed as well as a score for the risk of poor adherence. RESULTS: Ninety patients returned analyzable questionnaires: 65 (72.2%) thought a pharmaceutical consultation would be useful. They felt it should cover in priority the following subjects: drug interactions (51%), secondary effects (49%), and what to do after forgetting a dose (44%). Treatment was perceived as positive by 82 patients (91%) and tolerated well by 57 (65%). Sixty patients (66.3%) reported that they occasionally forgot a dose, 37 (41.3%) that they regularly did. The results showed good adherence by 61.3% and poor adherence by 38.5%. Risk of non-adherence was significantly associated with three factors: the number of pills to take, the number of daily doses, and the length of the treatment. CONCLUSION: Our survey shows the interest of consultations with pharmacists as a clinical service. By reinforcing the patient's understanding, these can complete and supplement the physician's explanation and instructions on pharmaceutical topics, especially those that could not be addressed during the clinical visit. The main aim of this process is to improve adherence, which is a key element in treatment efficacy.

Environmental contamination with cytotoxic drugs in healthcare using positive air pressure isolators.

Occupational exposure to cytotoxic drugs of hospital personnel involved in their preparation and administration is a major issue: ever since the introduction of protective measures in recent decades, the handling of these drugs has always been referred to as an occupational health hazard. Isolator technology was one of the protective equipments aimed at providing safe handling, but it has not yet been studied regarding contamination. The present study evaluates surface contamination with four cytotoxic drugs [cyclophosphamide (CP), ifosfamide (IF), 5 fluorouracil (5FU) and methotrexate (MTX)] by wipe sampling in two hospital pharmacies. Wipe samples were taken from work surfaces both located inside and outside the isolators. In addition, working gloves, the surface of infusion bags filled with 5FU or CP, and gloves used in simulation of drug administration were analyzed. Contamination was routinely found inside the isolators but rarely outside the isolators, indicating that the isolator technology is offering good protection of the cytotoxic drug handlers as well as the environment during preparation. On the other hand, contamination was found on the surfaces of infusion bags and gloves in contact with infusion bags filled with cytotoxic drugs. Consequently, personal protective equipment is still recommended during the manipulation and administration of the drugs because of potentially contaminated drug vials and final products.

The influence of long emersion on biota, ammonium fluxes and nitrification in intertidal sediments of Marennes-Oléron Bay, France.

A comparative study between waterlogged and reflooded intertidal sediments was undertaken in March and June 1999 through statistical analysis of selected sediment parameters (biota, salinity, O2, Eh), pool sizes and benthic fluxes of nutrients (NH4+, NO2-, NO3-) and nitrification rates. In March samples, absence of polychaetes and oligochaetes from upper sediment horizons were due to erosional events sweeping away surface sediments. Presence of richer annelid assemblages in June samples indicated more stable hydrodynamic conditions that favoured the development of benthic microalgae biofilms. Dewatering of sediments during a 3-day emersion period promoted a salinity rise on top layers, migration of pore water ions towards the sediment surface, and created sediment fissures that accelerated water exchange on reflooding. Reflooded and waterlogged sediment systems were comparable with respect to the release of NH4+ to overlying water but were different with respect to nitrification rates. Sediment-water NH4+ fluxes were higher (P = 0.011) in March (3.3 mmol m(-2) day(-1) compared to June (1.4 mmol m(-2) day(-1) due to higher macrofauna biomasses and lower benthic microalgae concentrations in March samples. Potential nitrification rates (range from 19 to 60 mmol NO3- (-2) day(-1)) were not statistically different between March and June. A thinner oxic layer in reflooded compared with waterlogged systems reflects a decrease of O2 diffusion into sediment at high salinities which resulted in the fall of the actual nitrification rates (P < 0.05). Our data suggest that long term dessication of intertidal sediments may depress the nitrification process at the ecosystem level.

Carboplatin and oxaliplatin decomposition in chloride medium, monitored by XAS.

The stability of carboplatin and oxaliplatin aqueous solutions has been studied under different chloride ions concentration and pH conditions. For both compounds, we demonstrate the chloration of the platinum first coordination shell.

Effect of the granulation process on nitrofurantoin granule characteristics.

We studied four granulation methods on the same quantitative and qualitative formula: wet massing by forced agglomeration (Lödige) and free agglomeration (Glatt); and dry massing by slugging and roller compaction technique. Three different particle sizes of nitrofurantoin (bioinequivalent drug) were used. The nitrofurantoin particle size has a very low influence on the physical characteristics of the granules. The granulating process influenced the binding of the particles. Granules processed using the wet granulating method were harder than those made by dry process. Lödige granules were more bonded than Glatt granules. Granules prepared by dry massing presented broken particles. The surface area and the porosity of Glatt granules were the most important parameters. Dissolution studies must be effected to make a correlation between the physical results and the dissolution rates. It is necessary to effect a new validation and a comparison of the results when a new granulating apparatus is used.

Effect of fat substitutes, sucrose polyester and tricarballylate triester, on digitoxin absorption in the rat.

The effect of non-absorbable fat substitutes (sucrose polyester (SPE) and tricarballylate triester (TCTE)) on [3H]digitoxin intestinal absorption was studied in the rat using a small intestine in-situ perfusion technique. The effect of SPE and TCTE was compared with that of sunflower oil, oleic acid, and saline. After 120 min perfusion, 5% SPE emulsion significantly reduced (P < 0.001) digitoxin absorption compared with all other treated groups. Five per cent TCTE emulsion had a less marked effect than SPE (P = 0.0002) and did not differ from sunflower oil. No difference was found between saline and 5% oleate emulsion, which did not reduce digitoxin absorption compared with other treated groups (P < 0.02). When taurocholic acid and lipase were added, results for the saline-, TCTE-, and SPE-treated groups were similar to those above, but the sunflower oil-treated group showed significantly enhanced (P < 0.01) digitoxin absorption. Thin-layer chromatography of the lipid phases showed hydrolysis of sunflower oil in the presence of taurocholic acid and lipase, but not of TCTE or SPE. The inhibitory effect of the non-absorbable fat substitutes on digitoxin absorption could be related to drug sequestration by the persistent oil phase constituted by the undigested and then unabsorbed fat substitutes. That part of digitoxin dissolved in the undigested oil phase is consequently unavailable for intestinal absorption.

[The influence of fat emulsions in ternary mixing during total parenteral feeding on biological and galenic parameters]. / Influence de l'émulsion lipidique en mélange ternaire lors de la nutrition parenterale totale sur les paramètres galéniques et biologiques.

Visual and microscopic inspection, pH, osmolality, measurements of particle size were made on one formulation of parenteral admixture. Based on examination of particle size distribution, admixtures prepared from Intrapilide or Ivelip were stable for up to four days. The results of visual and microscopic inspection in case of using Endolipide concluded to a shorter stability in that case. In the second part of this work the two fat emulsions Intralipide and Ivelip were studied to blow out any clinical or biochemical differences between two groups of patients. This clinical study was carried on fourty two patients recovering from digestive surgery. Patient metabolic parameters such as albumin and prealbumin remained the same in the two groups. The serum alkaline phosphatase has significantly been increasing in group Ivelip. Serum phosphoremia has been increasing in group Intralipide.

Immunohistochemical localization of type IV collagen in mouse tooth germ: an ultrastructural study.

Localization of type IV collagen was analyzed at the ultrastructural level in mouse embryonic molars by using a preembedding technique. Cryostat sections were incubated with type IV collagen antibody and then treated with the peroxidase-antiperoxidase complex. This antibody was visualized at the epithelio-mesenchymal interface. Labeling was intense and uniformly distributed throughout the basement membrane. However, it was mainly restricted to the lamina densa. No immunostaining was detectable in the lamina lucida but it was crossed by fine filaments that appeared as projections from the lamina densa to the epithelial cell plasma membrane. At the mesenchymal aspect of the basement membrane, projections of labeled material extended from the lamina densa in the underlying dental mesenchyme. At the presecretory stage of odontoblasts, these projections were in close connection with mesenchymal cell processes.