The use of sentinel lymph node biopsy in the treatment of breast ductal carcinoma in situ: A Danish population-based study

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Emil Villiam Holm-Rasmussen, Maj-Britt Jensen, Eva Balslev, Niels Kroman, Tove Filtenborg Tvedskov
ObjectivesThe risk of axillary metastases in breast cancer patients with only ductal carcinoma in situ (DCIS) is low. Thus, axillary staging with sentinel lymph node biopsy (SLNB) should only be used according to the current guidelines to avoid over-treatment and unnecessary morbidity. In the present study, the use of SLNB in patients with DCIS was evaluated nationally and compared across Danish departments.Material and methodsA register-based study was conducted using the Danish Breast Cancer Group database. The use of SLNB in DCIS patients according to year of diagnosis, age at diagnosis, size of lesion, Van Nuys classification, palpability, location and department of surgery was evaluated. The chi-squared test was used to test differences between the groups.ResultsData from 2618 Danish female patients diagnosed with DCIS between 2004 and 2015 were included; 54.3% of patients underwent SLNB. The use of SLNB increased from 26.6% in 2004 to 65.1% in 2015. A total of 1877 (71.7%) patients underwent breast-conserving surgery (BCS), and 577 (22.0%) underwent mastectomy, of which 43.9% and 86.0% respectively had a concomitant SLNB. The SLNB was performed in 23.8% of 454 patients not included by the guidelines. The use of SLNB in combination with BCS differed significantly between departments ranging from 19.7% to 63.8%. A significant difference in the use of SLNB with BCS and mastectomy according to department capacity (high-volume departments versus low-volume departments) was observed.ConclusionThe use of SLNB in patients with DCIS and adherence to the Danish national guidelines varies among Danish breast surgery departments. To optimise the axillary treatment of patients with DCIS, an improved compliance to the national DCIS guidelines is necessary.



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Identification of single nucleotide polymorphisms of the PI3K-AKT-mTOR pathway as a risk factor of central nervous system metastasis in metastatic breast cancer

Publication date: Available online 2 November 2017
Source:European Journal of Cancer
Author(s): Emilie Le Rhun, Nicolas Bertrand, Aurélie Dumont, Emmanuelle Tresch, Marie-Cécile Le Deley, Audrey Mailliez, Matthias Preusser, Michael Weller, Françoise Revillion, Jacques Bonneterre
IntroductionThe PI3K-AKT-mTOR pathway may be involved in the development of central nervous system (CNS) metastasis from breast cancer. Accordingly, herein we explored whether single nucleotide polymorphisms (SNPs) of this pathway are associated with altered risk of CNS metastasis formation in metastatic breast cancer patients.MethodsThe GENEOM study (NCT00959556) included blood sample collection from breast cancer patients treated in the neoadjuvant, adjuvant or metastatic setting. We identified patients with CNS metastases for comparison with patients without CNS metastasis, defined as either absence of neurological symptoms or normal brain magnetic resonance imaging (MRI) before death or during 5-year follow-up. Eighty-eight SNPs of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian (or mechanistic) target of rapamycin (mTOR) pathway genes were selected for analysis: AKT1 (17 SNPs), AKT2 (4), FGFR1 (2), mTOR (7), PDK1 (4), PI3KR1 (11), PI3KCA (20), PTEN (17), RPS6KB1 (6).ResultsOf 342 patients with metastases, 207 fulfilled the inclusion criteria: One-hundred-and-seven patients remained free of CNS metastases at last follow-up or date of death whereas 100 patients developed CNS metastases. Among clinical parameters, hormonal and human epidermal growth factor receptor-2 (HER2) status as well as vascular tumour emboli was associated with risk of CNS metastasis. Only PI3KR1-rs706716 was associated with CNS metastasis in univariate analysis after Bonferroni correction (p < 0.00085). Multivariate analysis showed associations between AKT1-rs3803304, AKT2-rs3730050, PDK1-rs11686903 and PI3KR1-rs706716 and CNS metastasis .ConclusionPI3KR1-rs706716 may be associated with CNS metastasis in metastatic breast cancer patients and could be included in a predictive composite score to detect early CNS metastasis irrespective of breast cancer subtype.



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Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Alexander Baraniskin, Jean-Luc Van Laethem, Lucjan Wyrwicz, Ulrich Guller, Harpreet S. Wasan, Tamara Matysiak-Budnik, Thomas Gruenberger, Michel Ducreux, Fatima Carneiro, Eric Van Cutsem, Thomas Seufferlein, Wolff Schmiegel
Background and scopeIn the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use.MethodologyOpinion leaders and experts from diverse nationalities selected on scientific merit were asked to answer to a prepared set of questions about the current status of molecular diagnostics in different GI cancers. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine.ResultsPreselected molecular genetic biomarkers that are described and disputed in the current medical literature in different GI cancers were debated, and recommendations for clinical routine practice were made whenever possible. Furthermore, the preanalytical variations were commented and proposals for quality controls of biospecimens were made.ConclusionThe current article summarises the recommendations of the expert committee regarding prognostic and predictive molecular genetic biomarkers in different entities of GI cancers. The briefly and comprehensively formulated guidelines should assist clinicians in the process of decision making in daily clinical practice.



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Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004–2013): Amassing data from independent Western populations provide etiologic clues

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Maeve Mullooly, Jeanne Murphy, Gretchen L. Gierach, Paul M. Walsh, Sandra Deady, Thomas I. Barron, Mark E. Sherman, Philip S. Rosenberg, William F. Anderson
The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER– breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004–2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER– cancers (EAPC: −3.43% per year [95% CI: −5.05, −1.78%/year]), as well as for specific age groups at diagnosis (<30–49, 50–64 and ≥65 years). ER+/HER2– cancers rose, ER+/HER2+ cancers were statistically flat and ER–/HER± cancers declined. Secular trends for ER± cancers in Ireland were like those previously observed. Stratification by HER2± expression did not substantively alter ER± trends. The divergence of ER± incidence rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER– breast cancers.



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Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): R. Cohen, O. Buhard, P. Cervera, E. Hain, S. Dumont, A. Bardier, J.-B. Bachet, J.-M. Gornet, D. Lopez-Trabada, S. Dumont, R. Kaci, P. Bertheau, F. Renaud, F. Bibeau, Y. Parc, D. Vernerey, A. Duval, M. Svrcek, Thierry André
BackgroundPatients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs.Patients and methodsMSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation.ResultsAmong 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (31%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44).ConclusionsLS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.



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Genetic polymorphisms in angiogenesis-related genes are associated with worse progression-free survival of patients with advanced gastrointestinal stromal tumours treated with imatinib

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Michiel C. Verboom, Jacqueline S.L. Kloth, Jesse J. Swen, Tahar van der Straaten, Judith V.M.G. Bovée, Stefan Sleijfer, Anna K.L. Reyners, Ron H.J. Mathijssen, Henk-Jan Guchelaar, Neeltje Steeghs, Hans Gelderblom
BackgroundImatinib 400 mg per day is first-line therapy for patients with gastrointestinal stromal tumours (GISTs). Although clinical benefit is high, progression-free survival (PFS) is variable. This study explores the relationship of single nucleotide polymorphisms (SNPs) in genes related to imatinib pharmacokinetics and pharmacodynamics and PFS in imatinib-treated patients with advanced GIST.MethodsIn 227 patients a pharmacogenetic pathway analysis was performed. Genotype data from 36 SNPs in 18 genes were tested in univariate analyses to investigate their relationship with PFS. Genetic variables which showed a trend (p < 0.1) were tested in a multivariate model, in which each singular SNP was added to clinicopathological factors.ResultsIn univariate analyses, PFS was associated with synchronous metastases (p = 0.0008) and the mutational status (p = 0.004). Associations with rs1870377 in KDR (additive model, p = 0.0009), rs1570360 in VEGFA (additive model, p = 0.053) and rs4149117 in SLCO1B3 (mutant dominant model, 0.027) were also found. In the multivariate model, significant associations and trends with shorter PFS were found for synchronous metastases (HR 1.94, p = 0.002), KIT exon 9 mutation (HR 2.45, p = 0.002) and the SNPs rs1870377 (AA genotype, HR 2.61, p = 0.015), rs1570360 (AA genotype, HR 2.02, p = 0.037) and rs4149117 (T allele, HR 0.62, p = 0.083).ConclusionIn addition to KIT exon 9 mutation and synchronous metastases, SNPs in KDR, VEGFA and SLCO1B3 appear to be associated with PFS in patients with advanced GIST receiving 400-mg imatinib. If validated, specific SNPs may serve as predictive biomarkers to identify patients with an increased risk for progressive disease during imatinib therapy.



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Long-term survival of sorafenib-treated FLT3-ITD–positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): S.K. Metzelder, T. Schroeder, M. Lübbert, M. Ditschkowski, K. Götze, S. Scholl, R.G. Meyer, P. Dreger, N. Basara, M.F. Fey, H.R. Salih, A. Finck, T. Pabst, A. Giagounidis, G. Kobbe, E. Wollmer, J. Finke, A. Neubauer, A. Burchert
BackgroundFms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)–positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available.MethodsWe performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD–positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy.FindingsWith a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years.InterpretationSorafenib may enable cure of a proportion of very poor risk FLT3-ITD–positive AML relapsing after allo-SCT.



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First-in-man phase I study assessing the safety and pharmacokinetics of a 1-hour intravenous infusion of the doxorubicin prodrug DTS-201 every 3 weeks in patients with advanced or metastatic solid tumours

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Patrick Schöffski, Jean-Pierre Delord, Etienne Brain, Jacques Robert, Herlinde Dumez, Jamal Gasmi, André Trouet
PurposeDTS-201 is a doxorubicin (Dox) prodrug that shows encouraging data in experimental models in terms of both efficacy and safety compared with conventional Dox. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose (RD) for clinical phase II studies and to assess potential anticancer activity of the compound.Experimental designDTS-201 was administered as a 1-hour infusion every 3 weeks in eligible patients with advanced solid tumours according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci schema.ResultsTwenty-five patients with a median age of 58 years (range, 30–72) were enrolled in the study. The median number of treatment cycles was 2 (range, 1–8). DTS-201 was administered at four dose levels (DLs) ranging from 80 to 400 mg/m², which is equivalent to 45–225 mg/m² of conventional Dox. No dose-limiting toxicity (DLT) occurred at the first two DLs. Three DLTs were observed at DL3 and DL4 (diarrhoea for DL3, vomiting and neutropenia for DL4). DL4 (400 mg/m²) was considered the maximum tolerated dose. Myelosuppression was the main toxicity, and NCI-CTC grade III–IV neutropenia was common at RD. Non-haematological adverse reactions were mild to moderate and included nausea, anorexia, asthenia and alopecia. No treatment-related severe cardiac adverse events were observed.ConclusionsDTS-201 is well tolerated and safe in heavily pretreated solid tumour patients. A high equivalent dose of Dox could be delivered without severe drug-related cardiac events. DTS-201 showed evidence of clinical activity with a confirmed partial response in a patient with soft-tissue sarcoma. The recommended phase II dose is 400 mg/m².



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Elderly patients with gastrointestinal stromal tumour (GIST) receive less treatment irrespective of performance score or comorbidity – A retrospective multicentre study in a large cohort of GIST patients

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Sheima Farag, Frits van Coevorden, Esther Sneekes, Dirk J. Grunhagen, Anna K.L. Reyners, Pieter A. Boonstra, Winette T. van der Graaf, Hans J. Gelderblom, Neeltje Steeghs
ObjectiveAlthough gastrointestinal stromal tumours (GIST) predominantly occur in older patients, data on treatment patterns in elderly GIST patients are scarce.MethodsPatients registered in the Dutch GIST Registry (DGR) from January 2009 until December 2016 were included. Differences in treatment patterns between elderly (≥75 years) and younger patients were compared. Multivariate analyses were conducted using logistic regression.ResultsData of 145 elderly and 665 non-elderly patients were registered (median age 78 and 60 years respectively). In elderly patients, performance score (WHO-PS) and age-adjusted Charlson comorbidity index (ACCI) were significantly higher (p < 0.05; p < 0.001), and albumin level significantly lower (p = 0.04).Hundred-and-nine (75.2%) elderly and 503 (75.6%) non-elderly patients had only localised disease. Surgery was performed in 57% of elderly versus 84% of non-elderly patients (p = 0.003, OR: 0.26, 95% CI: 0.11–0.63). No differences in surgery outcome or complications were found. Thirty-eight percent of elderly with an indication for adjuvant treatment did receive imatinib versus 68% of non-elderly (p = 0.04, OR: 0.47, 95% CI: 0.23–0.95).Thirty-six elderly and 162 non-elderly patients had metastatic disease. Palliative imatinib was equally given (mean dose 400 mg) and adverse events were mostly minor (p = 0.71). In elderly, drug-related toxicity was in 32.7% reason to discontinue imatinib versus 5.1% in non-elderly (p = 0.001, OR 13.5, 95% CI: 2.8–65.0). Median progression-free survival (PFS) was 24 months in elderly and 33 months in non-elderly (p = 0.10). Median overall survival (OS) was 34 months and 59 months respectively (p = 0.01).ConclusionsElderly GIST patients with localised disease receive less surgery and adjuvant treatment, irrespective of comorbidity and performance score. Drug-related toxicity results more often in treatment discontinuation. This possibly results in poor outcome.



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Revisiting the definition of dose-limiting toxicities in paediatric oncology phase I clinical trials: An analysis from the Innovative Therapies for Children with Cancer Consortium

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Francisco Bautista, Lucas Moreno, Lynley Marshall, Andrew D.J. Pearson, Birgit Geoerger, Xavier Paoletti
BackgroundDose-escalation trials aim to identify the maximum tolerated dose and, importantly, the recommended phase II dose (RP2D) and rely on the occurrence of dose-limiting toxicities (DLTs) during the first treatment cycle. Molecularly targeted agents (MTAs) often follow continuous and prolonged administrations, displaying a distinct toxicity profile compared to conventional chemotherapeutics, and classical DLT criteria might not be appropriate to evaluate MTAs' toxicity. We investigated this issue in children.MethodsThe Innovative Therapies for Children with Cancer Consortium (ITCC) phase I trials of novel anticancer agents between 2004 and 2015 were analysed. Data from investigational product, trial design, items defining DLT/RP2D were extracted. A survey on dose-escalation process, DLTs and RP2D definition was conducted among the ITCC clinical trials committee members.ResultsThirteen phase I trials with 15 dose-escalation cohorts were analysed. They explored 11 MTAs and 2 novel cytotoxics; 12 evaluated DLT during cycle 1. Definition of DLT was heterogeneous: Grade III–IV haematologic toxicities that were transient or asymptomatic and grade III–IV non-haematological toxicities manageable with adequate supportive care were often excluded, whereas some included dose intensity or grade II toxicities into DLT. None of the studies considered delayed toxicity into the RP2D definition.ConclusionDLTs should be homogeneously defined across trials, limiting the number of exceptions due to specific toxicities. Dose escalation should still be based on safety data from cycle 1, but delayed and overall toxicities, pharmacokinetic parameters and pharmacodynamic data should be considered to refine the final RP2D. The evaluation of long-term toxicity in the developing child cannot be adequately addressed in early trials.



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The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): M.A.C. Versluis, S. Marchal, A. Plat, G.H. de Bock, T. van Hall, M. de Bruyn, H. Hollema, H.W. Nijman
BackgroundHuman Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs).MethodsTissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses.ResultsUpregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37–0.89; HR 0.42 95% CI 0.25–0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09–0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70–106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression.ConclusionsTaken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations.



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Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Patrick Schöffski, Michael Gordon, David C. Smith, Razelle Kurzrock, Adil Daud, Nicholas J. Vogelzang, Yihua Lee, Christian Scheffold, Geoffrey I. Shapiro
BackgroundCabozantinib is an inhibitor of tyrosine kinases, including MET, vascular endothelial growth factor receptor, AXL and RET. This multi-cohort phase II randomised discontinuation trial explored anticancer activity of cabozantinib in nine tumour types.Patients and methodsCabozantinib was administered (100 mg, once daily) to patients with advanced, recurrent or metastatic cancers. Those with stable disease at week 12 were randomised 1:1 to cabozantinib or placebo. Primary end-points were objective response rate (ORR) at week 12 and progression-free survival (PFS) in the randomised phase.ResultsA total of 526 patients were enrolled. The highest ORR was observed in ovarian cancer (OC) (21.7%); the largest PFS benefit was observed in castration-resistant prostate cancer (CRPC) (median 5.5 versus 1.4 months for placebo; hazard ratio 0.14, 95% confidence interval: 0.04, 0.52). Disease control rates were >40% for CRPC, OC, melanoma, metastatic breast cancer (MBC), hepatocellular carcinoma (HCC) and non–small cell lung cancer. Median duration of response ranged from 3.3 (MBC) to 11.2 months (OC). Encouraging efficacy results and symptomatic improvements prompted early suspension of the randomised stage and conversion to open-label non-randomised expansion cohorts. Dose reductions to manage adverse events (AEs) occurred in 48.7% of patients. The most frequent grade III–IV AEs were fatigue (12.4%), diarrhoea (10.5%), hypertension (10.5%) and palmar-plantar erythrodysesthesia syndrome (8.7%).ConclusionsClinical antitumour activity of cabozantinib was observed in a subset of tumour types: CRPC and OC were evaluated further in expansion cohorts. Phase III programs were initiated in CRPC and HCC. Interpretation of efficacy outcomes was limited by early termination of the randomised portion of the trial.Trial registration numberNCT00940225.



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Silicon nanostructures for solar-driven catalytic applications

Publication date: Available online 4 November 2017
Source:Nano Today
Author(s): Dong Liu, Jun Ma, Ran Long, Chao Gao, Yujie Xiong
Silicon nanostructures exhibit prominent properties in solar energy conversion, which particularly offer tunable light harvesting and facile surface modification in comparison with their bulk counterparts. For this reason, silicon nanostructures have been exploited towards solar-driven catalysis, with extensive attention to the related working mechanisms. In this review article, we summarize the recent advances in the solar-driven catalytic applications based on silicon nanostructures. The key parameters to band engineering and surface modification, which hold the key to light harvesting and surface reactions, are specifically outlined for silicon nanostructures. We then overview the synthetic and fabrication methods for silicon nanostructures, which allow tailoring their key parameters. Based on the fundamental mechanisms and experimental methods, we elaborate on the typical applications of silicon nanostructures in solar-driven catalysis, including photocatalytic hydrogen production, dye degradation, organic reactions, CO2 conversion and N2 fixation, and photoelectrochemical water splitting. Finally, the challenges and opportunities for further development of silicon nanostructures for solar-chemical energy conversion are highlighted.

Graphical abstract

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One-dimensional nanomaterial-assembled macroscopic membranes for water treatment

Publication date: Available online 4 November 2017
Source:Nano Today
Author(s): Li Yu, Shuangchen Ruan, Xintong Xu, Rujia Zou, Junqing Hu
With the worldwide exponential development of population and industrialization, water pollution has become a serious issue for flora, fauna and human beings. The increasing concerns on environment sustainability require one to develop advanced materials and technologies for high-performance water treatment. Nanomaterials, exhibiting advantages of high specific surface areas and controlled architectures thereof have been vastly developed for improving the treatment speed, efficiency and selectivity. Membranes are favored materials for water decontamination due to their solute selectivity, handling robustness, and easy operational process without extra energy input. In this scenario, the combination of nanomaterials and membrane technology during water cleaning is required for both scientific research and real-world applications. One-dimensional (1D) nanomaterials-based membranes (e.g., self-assembled nanowires, nanobelts/ribbons, nanotubes, nanofibers) possessing interconnected open pore structures and large surface areas, were widely used to remove oily contaminants, toxic metal ions, emulsions, nanoparticles, small organic molecules such as antibiotics and dyes from water. This review focuses on the water treatment by using these nanomaterial-based membranes, which will be categorized based on their functionalities, i.e., adsorption, separation, filtration and photocatalytic degradation. In each section, representative studies and recent advances will be described. Further, future perspectives and challenges are summarized and put forward for developing multifunctional nanomaterial-based membranes for environmental remediation.

Graphical abstract

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Quantitative surface analysis of combined MRI and PET enhances detection of focal cortical dysplasias

Publication date: 1 February 2018
Source:NeuroImage, Volume 166
Author(s): Yee-Leng Tan, Hosung Kim, Seunghyun Lee, Tarik Tihan, Lawrence Ver Hoef, Susanne G. Mueller, Anthony James Barkovich, Duan Xu, Robert Knowlton
ObjectiveFocal cortical dysplasias (FCDs) often cause pharmacoresistant epilepsy, and surgical resection can lead to seizure-freedom. Magnetic resonance imaging (MRI) and positron emission tomography (PET) play complementary roles in FCD identification/localization; nevertheless, many FCDs are small or subtle, and difficult to find on routine radiological inspection. We aimed to automatically detect subtle or visually-unidentifiable FCDs by building a classifier based on an optimized cortical surface sampling of combined MRI and PET features.MethodsCortical surfaces of 28 patients with histopathologically-proven FCDs were extracted. Morphology and intensity-based features characterizing FCD lesions were calculated vertex-wise on each cortical surface, and fed to a 2-step (Support Vector Machine and patch-based) classifier. Classifier performance was assessed compared to manual lesion labels.ResultsOur classifier using combined feature selections from MRI and PET outperformed both quantitative MRI and multimodal visual analysis in FCD detection (93% vs 82% vs 68%). No false positives were identified in the controls, whereas 3.4% of the vertices outside FCD lesions were also classified to be lesional ("extralesional clusters"). Patients with type I or IIa FCDs displayed a higher prevalence of extralesional clusters at an intermediate distance to the FCD lesions compared to type IIb FCDs (p < 0.05). The former had a correspondingly lower chance of positive surgical outcome (71% vs 91%).ConclusionsMachine learning with multimodal feature sampling can improve FCD detection. The spread of extralesional clusters characterize different FCD subtypes, and may represent structurally or functionally abnormal tissue on a microscopic scale, with implications for surgical outcomes.



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The evaluative role of rostrolateral prefrontal cortex in rule-based category learning

Publication date: 1 February 2018
Source:NeuroImage, Volume 166
Author(s): Dmitrii Paniukov, Tyler Davis
Category learning is a critical neurobiological function that allows organisms to simplify a complex world. Rostrolateral prefrontal cortex (rlPFC) is often active in neurobiological studies of category learning; however, the specific role this region serves in category learning remains uncertain. Previous category learning studies have hypothesized that the rlPFC is involved in switching between rules, whereas others have emphasized rule abstraction and evaluation. We aimed to clarify the role of rlPFC in category learning and dissociate switching and evaluation accounts using two common types of category learning tasks: matching and classification. The matching task involved matching a reference stimulus to one of four target stimuli. In the classification task, participants were shown a single stimulus and learned to classify it into one of two categories. Matching and classification are similar but place different demands on switching and evaluation. In matching, a rule can be known with certainty after a single correct answer. In classification, participants may need to evaluate evidence for a rule even after an initial correct response. This critical difference allows isolation of evaluative functions from switching functions. If the rlPFC is primarily involved in switching between representations, it should cease to be active once participants settle on a given rule in both tasks. If the rlPFC is involved in rule evaluation, its activation should persist in the classification task, but not matching. The results revealed that rlPFC activation persisted into correct trials in classification, but not matching, suggesting that it continues to be involved in the evaluations of evidence for a rule even after participants have arrived at the correct rule.



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AnatomiCuts: Hierarchical clustering of tractography streamlines based on anatomical similarity

Publication date: 1 February 2018
Source:NeuroImage, Volume 166
Author(s): Viviana Siless, Ken Chang, Bruce Fischl, Anastasia Yendiki
Diffusion MRI tractography produces massive sets of streamlines that contain a wealth of information on brain connections. The size of these datasets creates a need for automated clustering methods to group the streamlines into meaningful bundles. Conventional clustering techniques group streamlines based on their spatial coordinates. Neuroanatomists, however, define white-matter bundles based on the anatomical structures that they go through or next to, rather than their spatial coordinates. Thus we propose a similarity measure for clustering streamlines based on their position relative to cortical and subcortical brain regions. We incorporate this measure into a hierarchical clustering algorithm and compare it to a measure that relies on Euclidean distance, using data from the Human Connectome Project. We show that the anatomical similarity measure leads to a 20% improvement in the overlap of clusters with manually labeled tracts. Importantly, this is achieved without introducing any prior information from a tract atlas into the clustering algorithm, therefore without imposing the existence of any named tracts.

Graphical abstract

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Caudal Intraparietal Sulcus and three-dimensional vision: A combined functional magnetic resonance imaging and single-cell study

Publication date: 1 February 2018
Source:NeuroImage, Volume 166
Author(s): Amir-Mohammad Alizadeh, Ilse Van Dromme, Bram-Ernst Verhoef, Peter Janssen
The cortical network processing three-dimensional (3D) object structure defined by binocular disparity spans both the ventral and dorsal visual streams. However, very little is known about the neural representation of 3D structure at intermediate levels of the visual hierarchy. Here, we investigated the neural selectivity for 3D surfaces in the macaque Posterior Intraparietal area (PIP) in the medial bank of the caudal intraparietal sulcus (IPS). We first identified a region sensitive to depth-structure information in the medial bank of the caudal IPS using functional Magnetic Resonance Imaging (fMRI), and then recorded single-cell activity within this fMRI activation in the same animals. Most PIP neurons were selective for the 3D orientation of planar surfaces (first-order disparity) at very short latencies, whereas a very small fraction of PIP neurons were selective for curved surfaces (second-order disparity). A linear support vector machine classifier could reliably identify the direction of the disparity gradient in planar and curved surfaces based on the responses of a population of disparity-selective PIP neurons. These results provide the first detailed account of the neuronal properties in area PIP, which occupies an intermediate position in the hierarchy of visual areas involved in processing depth structure from disparity.



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Encoding of natural timbre dimensions in human auditory cortex

Publication date: 1 February 2018
Source:NeuroImage, Volume 166
Author(s): Emily J. Allen, Michelle Moerel, Agustín Lage-Castellanos, Federico De Martino, Elia Formisano, Andrew J. Oxenham
Timbre, or sound quality, is a crucial but poorly understood dimension of auditory perception that is important in describing speech, music, and environmental sounds. The present study investigates the cortical representation of different timbral dimensions. Encoding models have typically incorporated the physical characteristics of sounds as features when attempting to understand their neural representation with functional MRI. Here we test an encoding model that is based on five subjectively derived dimensions of timbre to predict cortical responses to natural orchestral sounds. Results show that this timbre model can outperform other models based on spectral characteristics, and can perform as well as a complex joint spectrotemporal modulation model. In cortical regions at the medial border of Heschl's gyrus, bilaterally, and regions at its posterior adjacency in the right hemisphere, the timbre model outperforms even the complex joint spectrotemporal modulation model. These findings suggest that the responses of cortical neuronal populations in auditory cortex may reflect the encoding of perceptual timbre dimensions.



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Variation in longitudinal trajectories of cortical sulci in normal elderly

Publication date: 1 February 2018
Source:NeuroImage, Volume 166
Author(s): Xinke Shen, Tao Liu, Dacheng Tao, Yubo Fan, Jicong Zhang, Shuyu Li, Jiyang Jiang, Wanlin Zhu, Yilong Wang, Yongjun Wang, Henry Brodaty, Perminder Sachdev, Wei Wen
Sulcal morphology has been reported to change with age-related neurological diseases, but the trajectories of sulcal change in normal ageing in the elderly is still unclear. We conducted a study of sulcal morphological changes over seven years in 132 normal elderly participants aged 70–90 years at baseline, and who remained cognitively normal for the next seven years. We examined the fold opening and sulcal depth of sixteen (eight on each hemisphere) prominent sulci based on T1-weighted MRI using automated methods with visual quality control. The trajectory of each individual sulcus with respect to age was examined separately by linear mixed models. Fold opening was best modelled by cubic fits in five sulci, by quadratic models in six sulci and by linear models in five sulci, indicating an accelerated widening of a number of sulci in older age. Sulcal depth showed significant linear decline in three sulci and quadratic trend in one sulcus. Turning points of non-linear trajectories towards accelerated widening of the fold were found to be around the age between 75 and 80, indicating an accelerated atrophy of brain cortex starting in the age of late 70s. Our findings of cortical sulcal changes in normal ageing could provide a reference for studies of neurocognitive disorders, including neurodegenerative diseases, in the elderly.



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