| 1. |
- Apellániz-Ruiz, Maria, et al.
(författare)
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Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.
- 2017
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Ingår i: Clinical Cancer Research. - : American Association of Cancer Research. - 1078-0432 .- 1557-3265. ; 23:5, s. 1227-1235
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment.RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)).CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs.
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
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| 5. |
- Ferrando, Carlos, et al.
(författare)
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Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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| 6. |
- Mirza, Mansoor Raza, et al.
(författare)
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Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects
- 2022
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Ingår i: Cancer Research Communications. - : AMER ASSOC CANCER RESEARCH. - 2767-9764. ; 2:11, s. 1436-1444
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Tidskriftsartikel (refereegranskat)abstract
- In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA-mutated (non-gBRCAm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gBRCAm cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA-mutated (sBRCAm; HR, 0.27; 95% confidence interval, CI, 0.08–0.88) or BRCA wild-type (BRCAwt; HR, 0.47; 95% CI, 0.34–0.64) tumors. Patients with BRCAwt tumors with other non-BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13–0.77), as did patients with BRCAwt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35–0.70). When patients with BRCAwt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination–deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18–0.61) and in patients with homologous recombination–proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36–0.99) disease. Although patients with sBRCAm, other non-BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA/HRR mutation status or myChoice CDx GIS.Significance:We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline BRCA-mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non-BRCA HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo.
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| 7. |
- Ramos Riesco, Miguel, et al.
(författare)
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New Advances in the One-Dimensional Coordination Polymer Copper(II) Alkanoates Series: Monotropic Polymorphism and Mesomorphism
- 2015
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 15:4, s. 2005-2016
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Tidskriftsartikel (refereegranskat)abstract
- The polymorphism in the copper(II) alkanoates, recently discovered for one member, has been thoroughly studied for the whole series, from 3 to 16 C atoms. Three polymorphic phases have been found, all of them sharing the same molecular unit, the paddle-wheel, which grows forming a 1D coordination polymer or catena. The three polymorphs are defined by a different packing of these catenae and a specific arrangement of the alkyl chains. Ten new crystal structures of those compounds have been solved by high resolution powder diffraction and presented in this paper. The polymorphism in this series has been found to be monotropic and is responsible for the complex thermal behavior observed. The most characteristic feature, the endothermic−exothermic effect, has been explained for the first time in these compounds by a combination of data from differential scanning calorimetry (in normal and modulated modes), powder X-ray diffraction and Fourier transform infrared spectroscopy. These techniques, together with small-angle X-ray scattering and optical microscopy, were used to analyze the hexagonal columnar discotic liquid crystal phase of copper(II) alkanoates. Thus, new information has been found in the packing and stacking of the discs formed by the paddle-wheel units, also maintained in the mesophase.
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| 8. |
- Ramos Riesco, M., et al.
(författare)
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Study of the Polymorphism in Copper(II) Decanoate through Its Phase Diagram with Decanoic Acid, and Texture of the Columnar Thermotropic Liquid Crystal Developable Domains in This and Similar Systems
- 2015
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 15:1, s. 497-509
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Tidskriftsartikel (refereegranskat)abstract
- A new third polymorph of copper(II) decanoate has been found by two methods: from the crystallization of the saltacid solution and from a specific thermal treatment of the polymorph obtained in n-heptane. The new polymorph, whose crystal structure has been solved for the first time, is the most stable from the thermodynamic point of view. It presents a bilayer structure, but with two different types of paddle-wheels catenae with opposite orientations. This polymorphism as well as the temperature vs composition phase diagram of the system, [(1 - x) C9H21CO2H + (x) (C9H21CO2)(2)Cu], were solved by differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, pair distribution function, and optical microscopy. The singularities of the phase diagram are (a) a Krafft-like process of molecular association of the copper(II) decanoate into the acid solution, at about T = 361.5 K and x = 0.022 (forming salt-acid adducts of 1:1 stoichiometry); (b) a fusion transition as an invariant (T = 379.1 K) of the solid salt in excess from the copper(II) decanoate crystal phase to the discotic liquid crystal, forming homeotropic developable domains (seen for the first time in these systems) of the pure salt into the saturated acid solution. These domains are seen not only in the copper(II) decanoate but also in other members of the series, at high salt concentration in the corresponding acid solution, and allow identification of the hexagonal columnar discotic structure of the mesophase (with the exception of the copper(II) butanoate, where the tetragonal domains with tilted disks, paddle-wheels, were seen in the same salt-acid region).
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