Interaction of Neighborhood and Genetic Risk on Waist Circumference in African-American Adults: A Longitudinal Study.

BACKGROUND: Understanding determinants of metabolic risk has become a national priority given the increasingly high prevalence rate of this condition among U.S. adults. PURPOSE: This study's aim was to assess the impact of gene-by-neighborhood social environment interactions on waist circumference (WC) as a primary marker of metabolic risk in underserved African-American adults. Based on a dual-risk model, it was hypothesized that those with the highest genetic risk and who experienced negative neighborhood environment conditions would demonstrate higher WC than those with fewer risk factors. METHODS: This study utilized a subsample of participants from the Positive Action for Today's Health environmental intervention to improve access and safety for walking in higher-crime neighborhoods, who were willing to provide buccal swab samples for genotyping stress-related genetic pathways. Assessments were conducted with 228 African-American adults at baseline, 12, 18, and 24 months. RESULTS: Analyses indicated three significant gene-by-environment interactions on WC outcomes within the sympathetic nervous system (SNS) genetic pathway. Two interactions supported the dual-risk hypotheses, including the SNS genetic risk-by-neighborhood social life interaction (b = -0.11, t(618) = -2.02, p = .04), and SNS genetic risk-by-informal social control interaction (b = -0.51, t(618) = -1.95, p = .05) on WC outcomes. These interactions indicated that higher genetic risk and lower social-environmental supports were associated with higher WC. There was also one significant SNS genetic risk-by-neighborhood satisfaction interaction (b = 1.48, t(618) = 2.23, p = .02) on WC that was inconsistent with the dual-risk pattern. CONCLUSIONS: Findings indicate that neighborhood and genetic factors dually influence metabolic risk and that these relations may be complex and warrant further study. TRIAL REGISTRATION: NCT01025726.

Progress in the measurement and reduction of thermal noise in optical coatings for gravitational-wave detectors.

Coating thermal noise is a fundamental limit for precision experiments based on optical and quantum transducers. In this review, after a brief overview of the techniques for coating thermal noise measurements, we present the latest worldwide research activity on low-noise coatings, with a focus on the results obtained at the Laboratoire des Matériaux Avancés. We report new updated values for the Ta2O5, Ta2O5-TiO2, and SiO2 coatings of the Advanced LIGO, Advanced Virgo, and KAGRA detectors, and new results from sputtered Nb2O5, TiO2-Nb2O5, Ta2O5-ZrO2, MgF2, AlF3, and silicon nitride coatings. Amorphous silicon, crystalline coatings, high-temperature deposition, multi-material coatings, and composite layers are also briefly discussed, together with the latest developments in structural analyses and models.

Metabolisation of thiamethoxam (a neonicotinoid pesticide) and interaction with the Chronic bee paralysis virus in honeybees.

Pathogens and pesticides are likely to co-occur in honeybee hives, but much remains to be investigated regarding their potential interactions. Here, we first investigated the metabolisation kinetics of thiamethoxam in chronically fed honeybees. We show that thiamethoxam, at a dose of 0.25ng/bee/day, is quickly and effectively metabolised into clothianidin, throughout a 20day exposure period. Using a similar chronic exposure to pesticide, we then studied, in a separate experiment, the impact of thiamethoxam and Chronic bee paralysis virus (CBPV) co-exposure in honeybees. The honeybees were exposed to the virus by contact, mimicking the natural transmission route in the hive. We demonstrate that a high dose of thiamethoxam (5.0ng/bee/day) can cause a synergistic increase in mortality in co-exposed honeybees after 8 to 10days of exposure, with no increase in viral loads. At a lower dose (2.5ng/bee/day), there was no synergistic increase of mortality, but viral loads were significantly higher in naturally dead honeybees, compared with sacrificed honeybees exposed to the same conditions. These results show that the interactions between pathogens and pesticides in honeybees can be complex: increasing pesticide doses may not necessarily be linked to a rise in viral loads, suggesting that honeybee tolerance to the viral infection might change with pesticide exposure.

Evidence for positive selection and recombination hotspots in Deformed wing virus (DWV).

Deformed wing virus (DWV) is considered one of the most damaging pests in honey bees since the spread of its vector, Varroa destructor. In this study, we sequenced the whole genomes of two virus isolates and studied the evolutionary forces that act on DWV genomes. The isolate from a Varroa-tolerant bee colony was characterized by three recombination breakpoints between DWV and the closely related Varroa destructor virus-1 (VDV-1), whereas the variant from the colony using conventional Varroa management was similar to the originally described DWV. From the complete sequence dataset, nine independent DWV-VDV-1 recombination breakpoints were detected, and recombination hotspots were found in the 5' untranslated region (5' UTR) and the conserved region encoding the helicase. Partial sequencing of the 5' UTR and helicase-encoding region in 41 virus isolates suggested that most of the French isolates were recombinants. By applying different methods based on the ratio between non-synonymous (dN) and synonymous (dS) substitution rates, we identified four positions that showed evidence of positive selection. Three of these positions were in the putative leader protein (Lp), and one was in the polymerase. These findings raise the question of the putative role of the Lp in viral evolution.

The valence of the long-lasting emotional experiences with various handlers modulates discrimination and generalization of individual humans in sheep.

Between-farm variation in animal reactions to humans can reflect different management styles and behavioral tendencies among farmers. Animals are well known to discriminate among humans, but less clear is the key issue of whether they more or less easily generalize their experience from specific humans to others depending on management style. Here, we chose 2 contrasted management styles by known handlers: "gentle" management, that is, long-lasting exposure to positive human interactions (with limited negative interactions), and "aversive" management including long-lasting exposure to various negative human interactions (with only food delivery considered a positive interaction) and aversive events. Over a period of 19 wk, 15 female lambs were exposed to the gentle management treatment ("gently treated" group) and another 15 lambs ("aversively treated" group) were exposed to the aversive management treatment. To facilitate discrimination by animals, experimenters wore white clothes for aversive events and green clothes for farming handling (positive handling and feeding for the gently treated group and only feeding for the aversively treated group). Sheep perception of the human was assessed after the management period by submitting lambs from each group to 2 standardized tests: 1) the presence of a stationary human (familiar human in white vs. familiar human in green vs. unknown human) and 2) the presence of a moving human (familiar human in white vs. familiar human in green vs. unknown human). As expected, during the stationary human test, aversively treated lambs spent less time in the human zone (P<0.0001), showed greater latency to approach the human (P=0.05), and had fewer contacts with the human (P=0.05) than gently treated lambs. During the moving human test, aversively treated lambs also showed a greater escape distance from humans than gently treated lambs (P<0.0001). Aversively treated lambs showed the same fear responses towards familiar and unknown humans and tended to generalize their aversive experiences with one handler to all humans. In contrast, gently treated lambs seemed to discriminate familiar humans from unfamiliar humans. Different management styles could modulate farm generalization to humans in farm animals.

Can deuterium stable isotope values be used to assign the geographic origin of an auxiliary hoverfly in south-western France?

Deuterium δD isotopic analysis is increasingly being used to trace wildlife movement, and undoubtedly has much to offer in this respect, but questions still remain as to the feasibility and practicality of the method in ecology. Here we report our attempt to determine the geographic origin of an auxiliary hoverfly, Episyrphus balteatus, in south-western France. We used quantile regression to calculate the minimum separation distance, based on the International Atomic Energy Agency/World Meteorological Organization (IAEA/WMO) data, at which two insects could be said to originate from different latitudes with a given degree of confidence. We collected larvae in spring 2007 and 2009 to obtain the δD signal of indigenous hoverflies and we trapped adults during one complete year (from Dec. 2006 to Nov. 2007). The smallest separation distance calculated was about 1400 km in western Europe. Our results revealed greater variability in δD of adults in autumn than in spring. From this we infer an autumnal migration. Because of the presence of mountains and the Mediterranean Sea, the δD gradient in precipitation in western Europe is less clear than on the American continent, where it has been used successfully to infer geographical origins of animals under certain conditions. Despite the complications encountered in Europe, the minimum separation distance model proved a useful first step to obtain a first range of possible origins of E. balteatus and the application of the model to other arthropod species in Europe warrants investigation.

Gentle vs. aversive handling of pregnant ewes: I. Maternal cortisol and behavior.

The aim of the experiment was to study the effects of aversive vs. gentle handling in late pregnancy on maternal behavior of ewes. Sixteen Norwegian Dala ewes bearing twins were subjected to 10 min of either gentle (GEN--soft talking and calm behavior) or aversive (AVS--swift movements and shouting) handling twice a day during the last 5 weeks of pregnancy. Salivary cortisol was recorded before and after treatments. The following behaviors were recorded post-partum in the ewes: grooming duration, number of vocalizations and in the lambs: number of vocalizations, latency and duration of standing, latency and duration in udder-directed position. The ability of the ewe to follow her lamb carried away by a human was scored on day 1 and 7. After the treatment sessions, cortisol levels tended to increase in AVS ewes but not GEN ewes. At parturition, AVS ewes groomed their offspring for a longer duration than GEN ewes. AVS lambs tended to be heavier than GEN lambs at 24 h of age. Follow Scores from GEN ewes were higher than for the AVS ewes at day one, but no difference between treatment groups was detected after one week. These results show that aversively treated ewes increased their grooming behavior towards their offspring, but that fear of humans disrupted their ability to follow their lambs closely when carried away by a human. We conclude that the type of handling of ewes during pregnancy may have some impact on important maternal behaviors.

Gentle vs. aversive handling of pregnant ewes: II. Physiology and behavior of the lambs.

We compared the effects of aversive and gentle handling in late pregnant ewes on fearfulness, heart rate variability and spatial learning in lambs. Twenty-four Norwegian-Dala ewes were studied. Ewes were subjected to gentle (i.e. soft talking and calm behavior) or aversive handling (i.e. swift movements and shouting) for 10 min twice a day during the last five weeks of pregnancy. Lambs from aversively (AVS) or gently (GEN) treated ewes were tested at 4 weeks of age. Lamb behavior was recorded during a) a human approach test, composed of 4 min of isolation and 4 min of exposure to an unfamiliar human, b) an umbrella startle test followed by 5-min recording, and c) two repetitions of a maze test. In addition, heart rate variability was recorded telemetrically before and after the human and startle tests. The baseline heart rate variability measures suggested a lower influence of vagal stimulation in AVS lambs. In the human approach test, AVS lambs vocalized and explored the environment less, and were slower to approach the human. They also tended to have higher flight distances during the startle test than the GEN lambs. The prenatal treatment had no significant effect in the maze test. In conclusion, we showed that aversive handling of pregnant ewes increased fearfulness and reduced vagal tone in their progeny compared to GEN lambs. These effects can have consequences for how lambs cope with rearing conditions.

Social behavior and kin discrimination in a mixed group of cloned and non cloned heifers (Bos taurus).

For more than ten years, reproductive biotechnologies using somatic cell nuclear transfer have made possible the production of cloned animals in various domestic and laboratory species. The influence of the cloning process on offspring characteristics has been studied in various developmental aspects, however, it has not yet been documented in detail for behavioral traits. Behavioral studies of cloned animals have failed to show clear inter-individual differences associated with the cloning process. Preliminary results showed that clones favor each other's company. Preferential social interactions were observed among cloned heifers from the same donor in a mixed herd that also included cloned heifers and control heifers produced by artificial insemination (AI). These results suggest behavioral differences between cloned and non-cloned animals and similarities between clones from the same donor. The aim of the present study was to replicate and to extend these previous results and to study behavioral and cognitive mechanisms of this preferential grouping. We studied a group composed of five cloned heifers derived from the same donor cow, two cloned heifers derived from another donor cow, and AI heifers. Cloned heifers from the same donor were more spatially associated and interacted more between themselves than with heifers derived from another donor or with the AI individuals. This pattern indicates a possible kin discrimination in clones. To study this process, we performed an experiment (using an instrumental conditioning procedure with food reward) of visual discrimination between images of heads of familiar heifers, either related to the subjects or not. The results showed that all subjects (AI and cloned heifers) discriminated between images of familiar cloned heifers produced from the same donor and images of familiar unrelated heifers. Cattle discriminated well between images and used morphological similarities characteristic of cloned related heifers. Our results suggest similar cognitive capacities of kin and non kin discrimination in AI and cloned animals. Kinship may be a common factor in determining the social grouping within a herd.

[Locoregional anesthesia for pediatric surgery in remote rural settings: experience of an NGO in Bangladesh]. / Anesthésie locorégionale en chirurgie pédiatrique en milieu rural: expérience d'une ONG au Bangladesh.

Performing safe pediatric anesthesia in developing countries is a technical challenge for NGOs working in remote locations. The aim of this study is to describe our experience aboard a hospital ship working off the coast of northern Bangladesh. Anesthesia protocol records for a 3-year period were retrospectively reviewed. A total of 463 procedures were performed with no severe anesthetic complications. Regional anesthesia was performed in 83% of patients. It was carried out alone in 15% of patients and in association with IV or IM ketamine sedation in 68%. General anesthesia was performed using ketamine in 17% of patients. Tracheal intubation was carried out in only 3 cases. These findings indicate that regional anesthesia in association with ketamine as sedation agent is a simple and safe technique for pediatric anesthesia in remote rural settings.

Combined primary subintimal and endoluminal angioplasty for ischaemic inferior-limb ulcers in diabetic patients: 5-year practice in a multidisciplinary 'diabetic-foot' service.

INTRODUCTION: This study aims to assess the patency, the clinical success and the limb-salvage rates of combined subintimal (SA) coupled to endoluminal angioplasty (EA) as the initial treatment of ischaemic inferior-limb ulcers in diabetic patients and to study the influence of other concurrent factors in the tissue-healing process. MATERIALS AND METHOD: Since September 2002 until December 2007, a consecutive series of 176 limbs with manifold ischaemic wounds in 161 diabetic patients were treated by associated multilevel angioplasties in a multidisciplinary 'diabetic-foot team' (a third-line diabetic-care institution integrating two departmental hospitals). There were 98 associated SA with EA procedures, 26 re-vascularisations by single SA technique and 52 others including selective multilevel EAs that were retrospectively reviewed. The mean follow-up period was 22.1 months (in the range of 1-50 months) by clinical and duplex evaluation (every 6 months). RESULTS: The initial technical success was noted in 149 limbs (84%). For the single or associated SA procedures, 102 of 124 procedures were successful (82%) and 145 of 150 of the miscellaneous EAs (96%) evinced an equally favourable outcome. The 27 initially failed endovascular procedures (22 SA and five EA) required 16 surgical re-vascularisation, eight adjuvant endovascular procedures besides three amputations. A total of 21 secondary and five tertiary angioplasties were equally necessary during the entire follow-up period of these patients. The 30-day survival rate was 99% (one patient died from myocardial infarction). In a intention-to-treat analysis, the cumulative primary and secondary patencies at 12, 24, 36 and 48 months were 62%, 45%, 41% and 38%, together with 80%, 69%, 66% and 66%, respectively. The aggregate clinical success rates at the same intervals were 86%, 77%, 70% and 69%, while the corresponding limb-salvage proportions showed 89%, 83%, 80% and 80%, respectively. The primary patency was negatively affected at 1 and 4 years by the length of the occluded segment (>10 cm) and the end-stage renal disease (ESRD) (p<0.0001). The limb-salvage rates were unfavourably influenced at the same periods by the extent of tissue defects (>3 cm), the ESRD and the presence of osteomyelitis. In addition, at 4 years, the age (>70 years), the accompanying peripheral neuropathy, the bedridden status and the presence of cardiac failure (left ventricular ejection fraction (LVEF)<30%) appeared equally as negative predictors (p<0.0001) for wound healing and limb rescue. CONCLUSION: Primary angioplasty represents a low aggressive and efficacious method to improve the healing process in diabetic ischaemic ulcers. However, beyond appropriate re-vascularisation, even repetitive if necessary, achieving satisfactory limb-salvage rates probably implies a multidisciplinary control of the presenting risk factors for wound healing as well.

Large non-anastomotic false aneurysm on dacron aortobifemoral prosthesis solved by endovascular exclusion.

Aortic and iliac pseudo-aneurysms are infrequent but challenging complications after open surgical graft reconstructions, mostly having para-anastomotic localisations. The true corporeal peri-prosthetic false aneurysms are, up until now, very rarely documented presentations. We report the clinical case of an 8.8 cm diameter non-anastomotic and aseptic pseudo-aneurysm developed on aorto-bifemoral Dacron prosthesis in a symptomatic and high surgical risk patient. Considering the clinical presentation and the anatomical features, a chronic tear of the posterior prosthetic wall by prominent aortic remnant calcifications was evoked as the possible aetiology. An endovascular exclusion, using a tapered aorto-uni-iliac endograft coupled to a femoro-femoral bypass revascularisation, was technically successful. Despite scarce published clinical data focusing on the optimal treatment dedicated to this category of false aneurysm, this approach is thought to be beneficial in selected cases of high-risk surgical patients.

Dairy cattle exploratory and social behaviors: is there an effect of cloning?

While an increasing number of animals are produced by means of somatic cloning, behavioral studies on cloned animals are still rare. The aim of this study was to investigate whether the somatic cloning procedure has an influence on locomotion, exploratory, vocal and social behaviors of heifers. Ten heifers were used in the present study. Five of them were cloned heifers derived from somatic cells of three different Prim'Holstein cows and five others were same-age control heifers produced by artificial insemination. In addition to observations of social behaviors in the stable group, each animal was placed individually for a short time in an unfamiliar environment. Our results failed to show any statistical differences between clones and their controls both in frequencies of agonistic and non-agonistic behaviors. However, cloned heifers showed significantly more non-agonistic and less agonistic behaviors towards other cloned partners than towards control ones. This result also stood for control heifers. As far as their Hierarchical Index was concerned, three cloned heifers were highest ranking and two others lowest ranking. In this herd, social dominance appeared to be linked to body weight and age rather than to a cloning effect. In an unfamiliar environment, cloned and control subjects exhibited the same level of locomotion and vocalization. However, cloned heifers showed more exploratory behaviors than did control ones. This difference could be due to environmental factors during the postnatal period rather than to cloning.

[The 'awareness climbing': an educational board game for improving self-awareness following acquired brain injury]. / 'Escalada de la conciencia': un instrumento para mejorar la conciencia de enfermedad en pacientes con dano cerebral adquirido.

AIM: To establish the effectiveness of an educational board game for improving self-awareness following acquired brain injury. PATIENTS AND METHODS: The 'awareness climbing' is a board game format intervention for improving awareness of patients with acquired brain injury (ABI) and for facilitating the use of anticipatory and compensatory strategies. 17 patients with ABI (traumatic brain injury, 10; stroke, 5; others, 2) were included in a self-awareness rehabilitation program using the 'awareness climbing'. Self-awareness was assessed with the Self-Awareness of Deficit Interview (SADI) before and after game intervention. According to the SADI self-awareness consists of three-interdependent levels: intellectual awareness (impairments), emergent awareness (disability) and anticipatory awareness, which involve the client predicting when impairments will affect his or her performance. RESULTS: Initially five patients showed impaired intellectual awareness, four patients had difficulties on emergent awareness and nine patients showed deficits on anticipatory awareness. Intellectual awareness improved in 10 patients, while six patients experienced improvements in emergent awareness over the intervention period. The most striking change was an improvement in 70% of the sample (n = 11) in anticipatory awareness after game sessions. CONCLUSION: According to SADI scores we suggest that the 'awareness climbing' may be a useful tool for improving self-awareness after acquired brain injury.

Using stable isotopes to trace origin and host plants of an African polyphagous pest and an European beneficial insect.

Crop protection against insect pests requires first a good knowledge of the biology and ecology of the different pest species and the associated beneficials, in particular the spatial distribution of the populations. But the movement of insect populations in the landscape remains often poorly known and in some cases does not make it possible to know the role of the various cultivated and wild habitats in the dynamics of pest and useful insects. Stable isotopes are a tool contributing to the knowledge of host plants (13carbon/12carbon) as well as geographical origin of insects (1hydrogen/2hydrogen). The analysis of stable isotopic ratios has been performed in south-western France on populations of the hoverfly Episyrphus balteatus, one of the most important predators of the cereal aphids in Europe and on West African populations of the bollworm Helicoverpa armigera, an important polyphagous pest attacking cotton and vegetables in the Old World. Methodology, preliminary results and perspectives given by stable isotopes are presented here.

[Anoxic encephalopathy after ultraviolet radiation session: follow-up and results]. / Encefalopatía hipoxico-isquémica tras sesión de rayos ultravioleta: evolución y seguimiento.

Anoxic encephalopathy is the consequence of acute cerebral oxygen deprivation usually generated by cardiac arrest and/or respiratory failure. Recently an interesting case of one patient with cerebral anoxia after ultraviolet radiation session has been published. This paper shows the clinical evolution of this patient after inclusion in a multidisciplinary rehabilitation program, which included treatment of the psychopathological, neuropsychological and functional impairments that this pathology often generates. Over successive decades cerebral anoxia has come to be identified principally as one of the most significant causes of an isolated amnesia syndrome. Our patient presented at baseline intense difficulties in every verbal and visual memory processes associated with moderate impairments in sustained, selective and shifting attention as well as temporal disorientation. Compensation of memory deficit was the main rehabilitation strategy used in this case. This rehabilitation approach was possible thanks to the high degree of self-awareness of memory deficits shown by the patient and the selective impairment of memory with partial preservation of the rest of cognitive functions. This particular case gives us the opportunity to show the multidisciplinary approach of cognitive rehabilitation and the process of reintegration to social activities and to productive work even when deficits persist.

Glass vials for small volume parenterals: influence of drug and manufacturing processes on glass delamination.

PURPOSE: Studies were initiated to examine the effect of formulation and process variables on the delamination process and also the influence of the glass manufacturing process, supplier, and glass surface treatment. METHODS: Stress testing was performed by exposing filled vials to multiple sterilization cycles followed by accelerated stability testing. Delamination incidence was determined by visual examination, light obscuration (HIAC), and microscopical methods. The inner surface of vials from each supplier and lot were also examined by scanning electron microscopy. RESULTS: Vials sourced from Supplier A had smooth surfaces as demonstrated by SEM examination, whereas vials sourced from Suppliers B and C displayed extensive surface imperfections such as pitting and/or deposits. These imperfections were localized to the vial wall, adjacent to the vial bottom, and increased with sulfate treatment. Delamination incidence increased in those vial lots with increased surface imperfections. Thus, vials sourced from Supplier A had the lowest frequency of delamination. Sulfate treatment and high pH increased delamination incidence to as high as 100%. CONCLUSION: These results demonstrate the importance of the surface morphology created during the vial forming process. Given the diferences observed, final vial selection should include extensive microscopical and product stress testing studies on multiple vial lots.

[Palpable mantel cell lymphoma in the breast]. / Localisation mammaire et palpébrale d'un lymphome du manteau.

BACKGROUND: Extranodal involvement is not unusual in mantle cell lymphoma (MCL) which accounts for 6% of non-Hodgkin's lymphomas. Simultaneous localization in the eyelid and in the breast, as observed in our case, is however exceptional. CASE REPORT: Chronic lymphoid leukemia (CLL) was suspected in a 71-year-old woman with asthenia, a cervical and axillary nodal enlargement and elevated lymphocyte count. Blood immunoflow cytometry analysis, occurrence of rapidly growing tumors involving the two breasts and eyelids and cytogenetic and molecular features led to the diagnosis of MCL. A very good partial remission was obtained with second-line polychemotherapy composed of cytarabin, cisplatin and dexamethasone, but lasted only 3 months after the end of 6 cycles. DISCUSSION: Primary breast and eyelid lymphomas are rare. Such localizations are exceptional in MCL and are signs of aggressive disease. Before extra-nodal involvement, MCL may simulate banal CLL. Therefore, systematic immunohistochemistry and if necessary molecular analysis are useful for early diagnosis of MCL. Prognosis is particularly poor. Conventional chemotherapy cannot provide cure of MCL and median survival is 48 months. For this reason, high-dose chemotherapy with stem cell graft has to be discussed in young patients. MCL is currently characterized by Bcl1 rearrangement, t(11-14) translocation and cyclin D1 overexpression among small B-cell lymphomas in recent REAL- and WHO-classifications.

Dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.

This dose-finding study was designed to determine the maximum tolerated dose (MTD), efficacy and toxicity of combined paclitaxel and carboplatin in 35 previously untreated patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel was given as a 3-h infusion at escalating dose levels (100-250 mg/m2) immediately followed by carboplatin as a 30-min infusion (325 or 350 mg/m2) every 3 weeks. The dose-limiting toxicity, paresthesia, occurred at the highest dose level, therefore the recommended dose was established one level below (paclitaxel 225 mg/m2 with carboplatin 325 mg/m2). Neutropenia was the most common hematotoxicity; dose dependency was not apparent. Two patients, at different dose levels, had febrile neutropenia. Thrombocytopenia was rare. Non-hematological toxicities grade 3 or higher included infection, anorexia, alopecia and paresthesia. One patient had a hypersensitivity reaction (transient hypotension). The overall response rate was 23% and median survival time was 7.5 months. Promising activity and acceptable toxicity supports the development of this combination as a useful chemotherapeutic option in advanced NSCLC.