Pulmonary Recruitment Maneuver Reduces Shoulder Pain and Nausea After Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Pain and nausea are common after laparoscopic surgery. This prospective, randomized, controlled trial aimed to investigate postoperative pain and as a secondary endpoint nausea, when performing a ventilator-piloted Pulmonary Recruitment Maneuvre (PRM) at the end of laparoscopic cholecystectomy. METHOD: Patients having elective laparoscopic cholecystectomy were randomized to either ordinary exsufflation or ventilator-piloted PRM, to evacuate intra-abdominal carbon dioxide (CO2) before abdominal closure. A questionnaire with numeric rating scales (NRS) was utilized to evaluate pain and nausea at five occasions during 48 h following surgery. Analgesic and antiemetic treatment was also analyzed. RESULTS: 147 patients were analyzed, 76 receiving PRM and 71 controls. Overall pain was well controlled, with no significant difference between the groups regarding incidence (P=0.149) nor intensity (P=0.739). Incidence of shoulder pain was lower in the PRM group during the 48 postoperative hours, 44.7% versus 63.4% (P=0.023). The number needed to treat (NNT) to reduce shoulder pain was 6 (95% Confidence Interval, CI, 2.9-35.5) for the 48-h period. Incidence of nausea was lower in the PRM group during the 48-h period, 51.3% versus 70.4% (P=0.018). NNT was 6 (95% CI 2.9-27.4) for the 48-h period. Nausea intensity was lower in the PRM group during the 48 h (P=0.025). Fewer in the PRM population required antiemetics, 25.0% versus 42.3% (P=0.027). CONCLUSION: A ventilator-piloted PRM at the end of laparoscopic cholecystectomy reduced incidence of shoulder pain, and incidence and intensity of nausea. Clinical trial registration www.clinicaltrials.gov . Identifier: NCT03026543.

HIV-1 drug resistance testing at second-line regimen failure in Arua, Uganda: avoiding unnecessary switch to an empiric third-line.

OBJECTIVES: The number of patients on second-line antiretroviral therapy is growing, but data on HIV drug resistance patterns at failure in resource-constrained settings are scarce. We aimed to describe drug resistance and investigate the factors associated with extensive resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), in patients failing second-line therapy in the HIV outpatient clinic at Arua Regional Referral Hospital, Uganda. METHODS: We included patients who failed on second-line therapy (two consecutive viral loads ≥1000 copies/mm3 by SAMBA-1 point-of-care test) and who had a drug resistance test performed between September 2014 and March 2017. Logistic regression was used to investigate factors associated with NRTI genotypic sensitivity score (GSS) ≤1. RESULTS: Seventy-eight patients were included: 42% female, median age 31 years and median time of 29 months on second-line therapy. Among 70 cases with drug resistance test results, predominant subtypes were A (47%) and D (40%); 18.5% had ≥1 major protease inhibitor mutation; 82.8% had ≥1 NRTI mutation and 38.5% had extensive NRTI resistance (NRTI GSS ≤1). A nadir CD4 count ≤100/ml was associated with NRTI GSS ≤1 (OR 4.2, 95% CI [1.3-15.1]). Thirty (42.8%) patients were switched to third-line therapy, composed of integrase inhibitor and protease inhibitor (60% darunavir/r) +/- NRTI. A follow-up viral load was available for 19 third-line patients at 12 months: 84.2% were undetectable. CONCLUSIONS: Our study highlights the need for access to drug resistance tests to avoid unnecessary switches to third-line therapy, but also for access to third-line drugs, in particular integrase inhibitors. Low nadir CD4 count might be an indicator of third-line drug requirement for patients failing second-line therapy.

Impairment of quality of life in patients with antiphospholipid syndrome.

OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). CONCLUSION: Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient's perspective and to provide patients with the support they need.

ß-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma.

BACKGROUND: The use of ß-blockers for the management of hypertension has been recently associated with significant clinical benefits in cancer patients. Herein, we investigated whether ß-blockers could be used in combination with chemotherapy for the treatment of neuroblastoma. METHODS: Seven ß-blockers were tested for their antiproliferative and anti-angiogenic properties alone, and in combination with chemotherapy in vitro; the most potent drug combinations were evaluated in vivo in the TH-MYCN mouse model of neuroblastoma. RESULTS: Three ß-blockers (i.e., carvedilol, nebivolol and propranolol) exhibited potent anticancer properties in vitro and interacted synergistically with vincristine, independently of P-glycoprotein expression. ß-blockers potentiated the anti-angiogenic, antimitochondrial, antimitotic and ultimately pro-apoptotic effects of vincristine. In vivo, ß-blockers alone transiently slowed tumour growth as compared with vehicle only (P<0.01). More importantly, when used in combination, ß-blockers significantly increased the tumour regression induced by vincristine (P<0.05). This effect was associated with an increase in tumour angiogenesis inhibition (P<0.001) and ultimately resulted in a four-fold increase in median survival, as compared with vincristine alone (P<0.01). CONCLUSION: ß-blockers can increase treatment efficacy against neuroblastoma, and their combination with chemotherapy may prove beneficial for the treatment of this disease and other drug-refractory cancers.

[Pre-eclampsia prevention in 2018 in general population and in lupic women: At the dawn of a personalized medicine?] / Prévention de la pré-éclampsie en 2018 en population générale et chez la femme lupique : à l'aube d'une médecine personnalisée ?

Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring.

The transfer and persistence of petrol on car carpets.

The significance of the presence of petrol in motor vehicle fires has often been challenged due to the possibility of a natural occurrence of petrol residues inside the vehicle. Transfer and persistence studies were undertaken to investigate the potential transfer and persistence of petrol onto vehicle carpets through the 'normal' usage of motor vehicles. The results of the transfer study indicate that petrol may be transferred from the external environment in sufficient quantities via the shoes of drivers or passengers to be detected after a 24 h period, but not after 1 week. Low levels of petrol were detectable after 24 h on all carpet mats where the initial volume was 500 microL or more. The level of evaporation of the petrol detected increased with corresponding increases in the time period between transfer and analysis. The results of the persistence study indicate that small volumes of petrol (less than 100 microL) are unlikely to be detected on carpet after a 24 h period, and volumes of less than 1000 microL are unlikely to be detected on acoustic padding after this time period. Larger volumes may be detected after this period, but will generally not be detectable on either carpet or acoustic padding after 4 weeks. In each case, the petrol that is detected exhibits a chromatographic profile of greater than 60% evaporated petrol. These results demonstrate the significance of finding a large volume of fresh or slightly evaporated petrol on car carpet.

A cross sectional study of antiphospholipid-protein antibodies in patients with venous thromboembolism.

OBJECTIVE: To look for an association between venous thromboembolism (VTE) and antiphospholipid antibodies (aPL) in patients without Systemic Lupus Erythematosus (SLE) when implementing, beside conventional assays, new tests for aPL screening directed towards purified proteic targets. METHODS: We conducted a cross-sectional, hospital-based study of consecutive unselected outpatients. We compared VTE+ patients to VTE- among 398 consecutive unselected outpatients referred for clinical suspicion of VTE. To detect aPL, the following ELISAs were performed: 1) a conventional standardized ELISA 2) an improved APA assay, 3) an anti-Beta2GPI ELISA, 4) an anti-Annexin V ELISA, 5) an anti-Prothrombin ELISA. We sought an association between VTE and aPL through a quantitative (t-test) and a qualitative comparison (chi-square test, according to the cut-off values set as the 95th percentile of aPL distribution). First we conducted an analysis of all patients. Then we stratified them into 2 subgroups, with or without a wellknown risk factor for VTE (prolonged immobilization >72h, surgery or trauma within the past three months, current malignancy). RESULTS: 61% of patients were classified as VTE-positive. Before stratification, we did not find any significant association between the VTE status and aPL. However, after stratification, in the subgroup without risk factors for VTE, the frequency of positive values as regards the anti Prothrombin antibodies detection was significantly higher in VTE+ patients (p = 0,04). CONCLUSION: The presence of anti Prothrombin antibodies might be an independent risk factor of VTE. However systematic screening for aPL in non SLE patients referred for VTE suspicion at the time of the thrombo-embolic event has little clinical relevance.

Effects of delta5 polyunsaturated fatty acids of maritime pine (Pinus pinaster) seed oil on the fatty acid profile of the developing brain of rats.

Conifer (pine) seeds are a potential source of dietary oils, but their safety and nutritional properties are not well established. Conifer seed oils differ from common edible vegetable oils in having a series of unusual polyunsaturated fatty acids (PUFA) with a polymethylene-interrupted (PMI) double bond system and a double bond at the delta5 position. A rat study was conducted to assess whether delta5 PMI-PUFA of conifer seeds could alter the levels of n-6 and n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in mothers' milk and the developing brain of fetuses and pups. Feeding maritime pine (Pinus pinaster) seed oil (MPO) diet with a delta5 PMI-PUFA content of 1.4 g/100 g throughout pregnancy and lactation resulted in a large incorporation of delta5 PMI-PUFA in mothers' milk (5.1 +/- 0.5% of total fatty acids). The fetus (17 d old) and pup (22 d) brains, however, accumulated very little (0.6 and 0.4% of total fatty acids, respectively) delta5 PMI-PUFA. Mother's milk and pup's brain of the MPO group contained normal levels of 20:4n-6, 22:4n-6, and 20:5n-3 compared to a reference group of rats fed a fat blend of sunflower, high-oleic sunflower, and canola oils. The level of 22:6n-3, however, was slightly but significantly (P < 0.05) higher in milk and pup brain of the MPO group. These results show that delta5 PMI-PUFA of MPO exert no negative effect on the levels of n-6 and n-3 LC-PUFA in rat brain during its early development.

General characteristics of Pinus spp. seed fatty acid compositions, and importance of delta5-olefinic acids in the taxonomy and phylogeny of the genus.

The delta5-unsaturated polymethylene-interrupted fatty acid (delta5-UPIFA) contents and profiles of gymnosperm seeds are useful chemometric data for the taxonomy and phylogeny of that division, and these acids may also have some biomedical or nutritional applications. We recapitulate here all data available on pine (Pinus; the largest genus in the family Pinaceae) seed fatty acid (SFA) compositions, including 28 unpublished compositions. This overview encompasses 76 species, subspecies, and varieties, which is approximately one-half of all extant pines officially recognized at these taxon levels. Qualitatively, the SFA from all pine species analyzed so far are identical. The genus Pinus is coherently united--but this qualitative feature can be extended to the whole family Pinaceae--by the presence of delta5-UPIFA with C18 [taxoleic (5,9-18:2) and pinolenic (5,9,12-18:3) acids] and C20 chains [5,11-20:2, and sciadonic (5,11,14-20:3) acids]. Not a single pine species was found so far with any of these acids missing. Linoleic acid is almost always, except in a few cases, the prominent SFA, in the range 40-60% of total fatty acids. The second habitual SFA is oleic acid, from 12 to 30%. Exceptions, however, occur, particularly in the Cembroides subsection, where oleic acid reaches ca. 45%, a value higher than that of linoleic acid. Alpha-linolenic acid, on the other hand, is a minor constituent of pine SFA, almost always less than 1%, but that would reach 2.7% in one species (P. merkusii). The sum of saturated acids [16:0 (major) and 18:0 (minor) acids principally] is most often less than 10% of total SFA, and anteiso-17:0 acid is present in all species in amounts up to 0.3%. Regarding C18 delta5-UPIFA, taxoleic acid reaches a maximum of 4.5% of total SFA, whereas pinolenic acid varies from 0.1 to 25.3%. The very minor coniferonic (5,9,12,15-18:4) acid is less than 0.2% in all species. The C20 elongation product of pinolenic acid, bishomo-pinolenic (7,11,14-20:3) acid, is a frequent though minor SFA constituent (maximum, 0.7%). When considering C20 delta5-UPIFA, a difference is noted between the subgenera Strobus and Pinus. In the former subgenus, 5,11-20:2 and sciadonic acids are < or =0.3 and < or =1.9%, respectively, whereas in the latter subgenus, they are most often > or =0.3 and > or =2.0%, respectively. The highest values for 5,11-20:2 and sciadonic acids are 0.5% (many species) and 7.0% (P. pinaster). The 5,11,14,17-20:4 (juniperonic) acid is present occasionally in trace amounts. The highest level of total delta5-UPIFA is 30-31% (P. sylvestris), and the lowest level is 0.6% (P. monophylla). Uniting as well as discriminating features that may complement the knowledge about the taxonomy and phylogeny of pines are emphasized.

Fatty acid composition of Pinaceae as taxonomic markers.

Following our previous review on Pinus spp. seed fatty acid (FA) compositions, we recapitulate here the seed FA compositions of Larix (larch), Picea (spruce), and Pseudotsuga (Douglas fir) spp. Numerous seed FA compositions not described earlier are included. Approximately 40% of all Picea taxa and one-third of Larix taxa have been analyzed so far for their seed FA compositions. Qualitatively, the seed FA compositions in the three genera studied here are the same as in Pinus spp., including in particular the same delta5-olefinic acids. However, they display a considerably lower variability in Larix and Picea spp. than in Pinus spp. An assessment of geographical variations in the seed FA composition of P. abies was made, and intraspecific dissimilarities in this species were found to be of considerably smaller amplitude than interspecific dissimilarities among other Picea species. This observation supports the use of seed FA compositions as chemotaxonomic markers, as they practically do not depend on edaphic or climatic conditions. This also shows that Picea spp. are coherently united as a group by their seed FA compositions. This also holds for Larix spp. Despite a close resemblance between Picea and Larix spp. seed FA compositions, principal component analysis indicates that the minor differences in seed FA compositions between the two genera are sufficient to allow a clear-cut individualization of the two genera. In both cases, the main FA is linoleic acid (slightly less than one-half of total FA), followed by pinolenic (5,9,12-18:3) and oleic acids. A maximum of 34% of total delta5-olefinic acids is reached in L. sibirica seeds, which appears to be the highest value found in Pinaceae seed FA. This apparent limit is discussed in terms of regio- and stereospecific distribution of delta5-olefinic acids in seed triacylglycerols. Regarding the single species of Pseudotsuga analyzed so far (P. menziesii), its seed FA composition is quite distinct from that of the other two genera, and in particular, it contains 1.2% of 14-methylhexadecanoic (anteiso-17:0) acid. In the three genera studied here, as well as in most Pinus spp., the C18 delta5-olefinic acids (5,9-18:2 and 5,9,12-18:3 acids) are present in considerably higher amounts than the C20 delta5-olefinic acids (5,11-20:2 and 5,11,14-20:3 acids).

Chemical fingerprinting of unevaporated automotive gasoline samples.

The comparison of two or more samples of liquid gasoline (petrol) to establish a common origin is a difficult problem in the forensic investigation of arsons and suspicious fires. A total of 35 randomly collected samples of unevaporated gasoline, covering three different grades (regular unleaded, premium unleaded and lead replacement), were examined. The high-boiling fraction of the gasoline was targeted with a view to apply the techniques described herein to evaporated gasoline samples in the future.A novel micro solid phase extraction (SPE) technique using activated alumina was developed to isolate the polar compounds and the polycyclic aromatic hydrocarbons (PAHs) from a 200microl sample of gasoline. Samples were analysed using full-scan gas chromatography-mass spectrometry (GC-MS) and potential target compounds identified. Samples were then re-analysed directly, without prior treatment, using GC-MS in selected ion monitoring (SIM) mode for target compounds that exhibited variation between gasoline samples. Principal component analysis (PCA) was applied to the chromatographic data. The first two principal components (PCs) accounted for 91.5% of the variation in the data. Linear discriminant analysis (LDA) performed on the PCA results showed that the 35 samples tested could be classified into 32 different groups.

Chemical fingerprinting of gasoline. 2. Comparison of unevaporated and evaporated automotive gasoline samples.

Analysis of the C(0)- to C(2)-naphthalene compounds present in automotive gasoline using gas chromatography-mass spectrometry with selected ion monitoring (GC-MS (SIM)) and principal component analysis (PCA) was used to discriminate between different samples of gasoline. Phase one of this study explored the ability of this method to differentiate gasoline samples at different levels of evaporation. A total of 35 random samples of unevaporated gasoline, covering three different grades (regular unleaded, premium unleaded and lead replacement), were collected in Sydney, Australia and examined. The high-boiling C(0)- to C(2)-naphthalene compounds present in the gasoline were used to chemically fingerprint each sample at different levels of evaporation. Samples of 25, 50, 75 and 90% evaporated gasoline (by weight) were generated from the 35 samples of unevaporated gasoline. Analysis of the data by PCA followed by linear discriminant analysis (LDA) showed that the 35 samples formed 18 unique groups, irrespective of the level of evaporation. Good discrimination between gasoline samples that were collected on the same day was obtained. Phase two of this study examined the change in gasoline samples over time. The C(0)- to C(2)-naphthalene composition in 96 samples of gasoline collected from three service stations over a 16-week period was examined using the method described. In most cases, it was found that the C(0)- to C(2)-naphthalene profile changed from week to week, and from station to station. In a comparison of all 96 samples together it was found that the majority could be differentiated from one another. The application of the method to forensic casework is discussed.

Chemical fingerprinting of gasoline. Part 3. Comparison of unevaporated automotive gasoline samples from Australia and New Zealand.

A gas chromatography-mass spectrometry with selected ion monitoring (GC-MS (SIM)) method was used to discriminate samples of unevaporated gasoline collected from Auckland, New Zealand and Sydney, Australia. This method was applied to 28 samples of unevaporated gasoline, covering three different grades (regular unleaded, premium unleaded and premium plus unleaded), that were collected from service stations in Auckland, New Zealand in summer (February) and winter (August). The 14 samples of summer gasoline collected in New Zealand could be divided into seven unique groups. The 14 samples of winter gasoline from New Zealand could be divided into 14 unique groups. The 14 samples collected in New Zealand during February 2002 were then compared to 24 samples of unevaporated gasoline collected from service stations in Sydney, Australia during the same month. Most of the samples could be differentiated based on their country of origin.

Chlamydia pneumoniae IgG serological status and venous thromboembolism: a cross-sectional hospital based study.

OBJECTIVE: To search for a link between Chlamydia pneumoniae serological status and venous thromboembolic disease. METHODS: From March 1992 to October 1999, we conducted a cross-sectional hospital-based study of consecutive unselected outpatients referred to us for clinical suspicion of venous thromboembolism. We compared the Chlamydia pneumoniae serological status with respectively, the venous thromboembolism, the deep vein thrombosis and the proximal deep vein thrombosis status. RESULTS: Among 1193 patients registered for suspected venous thromboembolism, 1010 samples were available (499 negative and 511 positive patients for venous thromboembolism). Seventy-nine patients were Chlamydia pneumoniae positive. Our work failed to demonstrate any clear association between Chlamydia pneumoniae and venous thromboembolism status. Nevertheless, we identified a statistical difference regarding Chlamydia pneumoniae seropositivity and proximal vein thrombosis status (adjusted odds ratio of 1.70, CI95%: 1.05 to 2.77). CONCLUSION: The presence of Chlamydia pneumoniae antibodies might be a minor risk factor for venous thrombosis.

[Teaching ethics in French medical schools: evolution or revolution ?]. / Enseignement de l'éthique dans les UFR médicales françaises: évolution ou révolution?

Ethics was introduced as subject matter in French medical schools only recently despite a rich historical context where scientific legitimacy, humanistic exigencies and anglo-saxon influence have all played a role. Ten years after the thesis presented by Bastian in 1986, a survey of French medical schools shows that ethics has become an integral part of the curriculum. Ethics has tended to become a discipline on its own, separate from law and deontology. However, the lack of specific courses on concentration in the first years of the curriculum show that there is much room for growth in the discipline of medical ethics.

[ImmunoComb--reliability and reproducibility]. / ImmunoComb fiabilité et reproductibilité.

ImmunoComb is a solid phase in vitro immunological test for the measurement of serum or plasma total IgE. The technique was compared with PRIST for measurement of total IgE. The study also included reproducibility, on a test serum dilution both on a complete plate and plate sections. Statistically the conclusion is that ImmunoComb is a colourimetric test that gives the exact total IgE titre with good reproducibility. Use of a photometer greatly improves the sensitivity of assessing the results.

[The human basophil degranulation test. Attempt at determining its reliability]. / Etude du test de dégranulation des basophiles humains (TDBH). Essai de détermination de la fiabilité.

A single-blind assay was made between a laboratory in Paris and our own, in order to assess objectively the Human Basophil Degranulation test (TDBH). The study was made on 28 subjects. They presented with anaphylactic or systemic reactions to hymenoptera venom. The samples from these patients were sent to Paris without any other diagnostic information. Agreement of results between ANGERS and PARIS was very poor, at around 38.5%. Agreement between the TDBH at ANGERS and PARIS with other biological parameters and skin tests was also weak, at 41.7 to 55% in ANGERS and 45.8 to 58.3% in PARIS. The techniques used at ANGERS and PARIS were the same. Overall, TDBH does not seem to be either reliable or reproducible between two laboratories, in the special case of hypersensitivity to hymenoptera venoms.

A mathematical model for the administration of temozolomide: comparative analysis of conventional and metronomic chemotherapy regimens.

We propose a mathematical model that takes into account a classical maximum tolerated dose (MTD) chemotherapy regimen (whose primary targets are the tumor cells) as well as a metronomic chemotherapy regimen (whose primary targets are the tumor endothelial cells) for the administration of temozolomide (Temodal(®)) in order to compare the effectiveness of these two types of protocols. The model is built from 4 natural hypotheses: (H1) without treatment the tumor growth follows a Gompertz model, (H2) endothelial cells are more sensitive to temozolomide than cancer cells, (H3) the anti-angiogenic effect blocks tumor growth, and (H4) endothelial cells are more genetically stable than cancer cells and thus less likely to develop resistance to temozolomide. Then, we compared a conventional MTD regimen of 200 mg/m(2) temozolomide J1-J5 every 28 days with a daily metronomic regimen of 85 mg/m(2)/day for cycles of 42 days. Our mathematical model shows that the metronomic regimen induces tumor regression through anti-angiogenic effects while the MTD regimen fails to do so, due to the emergence of temozolomide resistance in cancer cells. Overall, our model is consistent with clinical observations and provides an interesting tool toward the personalization of anticancer treatments, through optimization of dose and schedule of chemotherapy based on individual patient characteristics.