Laryngeal Preservation Strategies in Locally Advanced Laryngeal and Hypopharyngeal Cancers.

For long, the treatment of locoregionally advanced laryngeal and hypopharyngeal squamous cell cancers (SCC) consisted of either total laryngectomy (TL) or definitive radiotherapy (RT). The development of induction cisplatin plus 5-fluorouracil (PF) and the correlation between chemosensitivity and radiosensitivity in previously untreated patients opened a new era of treatment aiming at laryngeal preservation (LP). The fundamental concept was to employ induction PF in order to select patients for subsequent treatment with either TL or RT according to tumor response to PF. The first two trials (VALGSG for laryngeal SCC and EORTC 24891 for hypopharyngeal SCC) concluded that such an approach could preserve nearly 60% of larynx without deleterious impact on survival. The EORTC 24954 trial compared 4 cycles of induction PF followed by RT in good responders vs. alternating PF-RT in laryngeal and hypopharyngeal SCC. There was no significant difference in 5-year overall survival with a functional larynx between the two arms (31 vs. 35%). The GORTEC 2000-01 trial compared induction PF to induction PF plus docetaxel (TPF) both followed by RT in good responders in larynx and hypopharynx SCC. The 5-year LP was significantly higher in the TPF arm (60 vs. 39%) but without a difference in survival. The RTOG 91-11 trial compared induction PF followed by RT in good responders vs. concurrent chemoradiotherapy (chemo-RT) vs. RT alone in laryngeal SCC. There was no significant difference in 5-year laryngectomy-free survival between the patients treated with induction chemotherapy (44%) vs. those treated with chemo-RT (47%), both being superior to RT alone (34%). At 5 years, LP was superior with chemo-RT: 84 vs. 71% with induction PF. Two phase II trials explored the role of cetuximab (E) in LP in laryngeal and hypopharyngeal SCC. The TREMPLIN trial compared RT+E or chemo-RT (RT + P) after TPF. The DeLOS-II trial compared TPE followed by RT+E vs. TP followed by RT. However, these trials failed to indicate an advantage for the incorporation of E in the treatment paradigm. To date, two approaches for LP have been validated: induction TPF followed by RT for laryngeal and hypopharyngeal SCC and concurrent chemo-RT for laryngeal SCC. An ongoing trial (SALTORL) is comparing these two approaches, induction TPF and chemo-RT, in laryngeal/ hypopharyngeal SCC

Surgery for Laryngopharyngeal SCC in the Era of Organ Preservation

Over the past decades, randomized clinical trials have assessed and validated the concept of larynx preservation. This new concept has obviously modified the treatment algorithm for laryngopharyngeal squamous cell carcinoma. However surgery for larynx and hypopharynx cancer remains indicated in many cases. Initial partial surgery is indicated for early diseases. This surgery may be performed endoscopically or openly. The results are excellent in terms of local control and function. Transoral robotic surgery is under evaluation. Initial radical surgery is indicated for advanced diseases in case of very infiltrative tumor, in case of cartilage destruction or when tolerance and/or compliance to chemotherapy-based approached is questionable. Larynx preservation is to be discussed between these two situations. In randomized trials evaluating the different larynx preservation strategies, a substantial number of larynxes could be preserved without compromising disease control or survival. The best approach in terms of quality of function preservation, overall acute and late toxicity, disease control and survival is still a matter of clinical research. It must be stressed that salvage surgery is a definite part of these larynx preservation protocols in order to maintain the ultimate disease control. This discussion underscored the need of a multidisciplinary decision making and the need of a coordinated clinical research

L’impact de la technologie informatique sur la main-d’oeuvre dans les organisations

Comment les dirigeants des entreprises québécoises perçoivent-ils les impacts de la technologie informatique sur la main-d’oeuvre dans leurs propres organisations? Nous exposons dans le cadre de cet article les résultats partiels d’une étude empirique à laquelle plus de 1 700 dirigeants ont participé. Cette recherche se situe donc dans une perspective strictement organisationnelle et non pas macro-économique. Les présents résultats indiquent que la taille mais non le secteur d’activité de l’entreprise, serait un facteur significatif à considérer lors de l’étude des variations du nombre d’emplois et de la productivité dans une organisation. De plus, il existerait des différences importantes selon les catégories d’employés.What is the impact of information technology on human resources in organizations as percieved by managers? This article provides empirical results from a survey of 1,708 organizations. The results indicate that firm size is a significant variable influencing the impact of technology on the number and productivity of employees. Futhermore, different categories of employees are affected differently

L’impact de la technologie informatique sur la main-d’oeuvre dans les organisations

What is the impact of information technology on human resources in organizations as percieved by managers? This article provides empirical results from a survey of 1,708 organizations. The results indicate that firm size is a significant variable influencing the impact of technology on the number and productivity of employees. Futhermore, different categories of employees are affected differently. Comment les dirigeants des entreprises québécoises perçoivent-ils les impacts de la technologie informatique sur la main-d’oeuvre dans leurs propres organisations? Nous exposons dans le cadre de cet article les résultats partiels d’une étude empirique à laquelle plus de 1 700 dirigeants ont participé. Cette recherche se situe donc dans une perspective strictement organisationnelle et non pas macro-économique. Les présents résultats indiquent que la taille mais non le secteur d’activité de l’entreprise, serait un facteur significatif à considérer lors de l’étude des variations du nombre d’emplois et de la productivité dans une organisation. De plus, il existerait des différences importantes selon les catégories d’employés.

Intangible Capabilities as Determinants of Advanced Manufacturing Technology Adoption in SMEs: Toward an Evolutionary Model

This paper investigates the relationship between intangible capabilities and further AMT adoption in 116 small manufacturing firms. Results indicate that skills of blue-collar workers, influences of customers and vendors, and motivations focussed on process improvement and customers are the strongest determinants of subsequent levels of adoption. Further, it is shown that strategic motivations moderate the relationships between technical skills and influences, and further AMT adoption. Preliminary support for an evolutionary model is also leading to a revised conceptual framework. Dans ce papier, la relation entre les compétences intangibles et l'adoption subséquente de technologies avancées de production est étudiée dans un échantillon de 116 petites entreprises manufacturières. Les résultats indiquent que les compétences des cols bleus et l'influence des clients et des fournisseurs de technologies sont dominantes. De plus, il semble exister certains indicateurs préliminaires suggérant l'existence d'un modèle évolutif.Learning model; Technology adoption; Small manufacturing firms, Modèles d'apprentissage; Adoption des technologies; Petites entreprises manufacturières

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (+/- SD) of 5.3 +/- 2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P = 0.02). The number of serious adverse events did not differ significantly between the treatment groups (P = 0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation

Inhibition of the β-lactamase BlaMab by avibactam improves the in vitro and in vivo efficacy of imipenem against mycobacterium abscessus

Mycobacterium abscessus pulmonary infections are treated with a macrolide (clarithromycin or azithromycin), an aminoglycoside (amikacin), and a β-lactam (cefoxitin or imipenem). The triple combination is used without any β-lactamase inhibitor, even though M. abscessus produces the broad-spectrum β-lactamase BlaMab. We determine whether inhibition of BlaMab by avibactam improves the activity of imipenem against M. abscessus. The bactericidal activity of drug combinations was assayed in broth and in human macrophages. The in vivo efficacy of the drugs was tested by monitoring the survival of infected zebrafish embryos. The level of BlaMab production in broth and in macrophages was compared by quantitative reverse transcription-PCR and Western blotting. The triple combination of imipenem (8 or 32 μg/ml), amikacin (32 μg/ml), and avibactam (4 μg/ml) was bactericidal in broth (<0.1% survival), with 3.2- and 4.3-log10 reductions in the number of CFU being achieved at 72 h when imipenem was used at 8 and 32 μg/ml, respectively. The triple combination achieved significant intracellular killing, with the bacterial survival rates being 54% and 7% with the low (8 μg/ml) and high (32 μg/ml) dosages of imipenem, respectively. In vivo inhibition of BlaMab by avibactam improved the survival of zebrafish embryos treated with imipenem. Expression of the gene encoding BlaMab was induced (20-fold) in the infected macrophages. Inhibition of BlaMab by avibactam improved the efficacy of imipenem against M. abscessus in vitro, in macrophages, and in zebrafish embryos, indicating that this β-lactamase inhibitor should be clinically evaluated. The in vitro evaluation of imipenem may underestimate the impact of BlaMab, since the production of the β-lactamase is inducible in macrophages

Increasing crop heterogeneity enhances multitrophic diversity across agricultural regions

International audienceAgricultural landscape homogenization has detrimental effects on biodiversity and key ecosystem services. Increasing agricultural landscape heterogeneity by increasing seminatural cover can help to mitigate biodiversity loss. However, the amount of seminatural cover is generally low and difficult to increase in many intensively managed agricultural landscapes. We hypothesized that increasing the heterogeneity of the crop mosaic itself (hereafter “crop heterogeneity”) can also have positive effects on biodiversity. In 8 contrasting regions of Europe and North America, we selected 435 landscapes along independent gradients of crop diversity and mean field size. Within each landscape, we selected 3 sampling sites in 1, 2, or 3 crop types. We sampled 7 taxa (plants, bees, butterflies, hoverflies, carabids, spiders, and birds) and calculated a synthetic index of multitrophic diversity at the landscape level. Increasing crop heterogeneity was more beneficial for multitrophic diversity than increasing seminatural cover. For instance, the effect of decreasing mean field size from 5 to 2.8 ha was as strong as the effect of increasing seminatural cover from 0.5 to 11%. Decreasing mean field size benefited multitrophic diversity even in the absence of seminatural vegetation between fields. Increasing the number of crop types sampled had a positive effect on landscape-level multitrophic diversity. However, the effect of increasing crop diversity in the landscape surrounding fields sampled depended on the amount of seminatural cover. Our study provides large-scale, multitrophic, cross-regional evidence that increasing crop heterogeneity can be an effective way to increase biodiversity in agricultural landscapes without taking land out of agricultural production

Social security and retirement around the world:Lessons from a long-term collaboration

Declining labor force participation of older men throughout the 20th century and recent increases in participation have generated substantial interest in understanding the effect of public pensions on retirement. The National Bureau of Economic Research's International Social Security (ISS) Project, a long-term collaboration among researchers in a dozen developed countries, has explored this and related questions. The project employs a harmonized approach to conduct within-country analyses that are combined for meaningful cross-country comparisons. The key lesson is that the choices of policy makers affect the incentive to work at older ages and these incentives have important effects on retirement behavior.</p