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Background Frameless stereotactic biopsy represents a minimally invasive procedure used for the histopathological diagnosis of brain tumors or to safely approach deep-seated lesions near eloquent areas not amenable for classical neurosurgical procedures. Traditionally, biopsy is performed relying on anatomical landmarks, but it can lead itself to intra- and postoperative complications, such as hemorrhage and fiber disruption. Diffusion tensor imaging (DTI) tractography represents a useful tool that can analyze the individual fiber tract conformation in cases of brain tumor and consequently identify the best biopsy trajectory, preserving white matter pathways. In our study, we present a novel technique that is based on the use of preoperative DTI for biopsy. Methods Between January 2018 and January 2020, data about patients who underwent frameless biopsy using DTI tractography were retrospectively reviewed. The inclusion criterion was adult patients eligible for elective surgery for a single or multiple deep-seated lesions with contraindications to complete surgical resection. Results We included 12 patients (mean age of 67.9 [±9.6] years). A single cranial lesion was detected in 7 cases, and multiple lesions in 5 cases. The use of DTI enabled the identification of white matter pathways in all cases and adjustment of the biopsy trajectory based on anatomical landmarks in 7 cases. Postoperative hematoma was reported in 1 case, and histological diagnosis was obtained in 11 cases. Conclusion According to our results, tractography is a useful tool that can enhance the safety of cerebral lesions biopsy sparing any fiber tract damages.

Brain surgery is required to ascertain the diagnosis of central nervous system lymphoma. We assessed the diagnostic yield and safety of the surgical procedures, the predictors of postoperative morbidity, and of overall survival.Observational single-institution retrospective cohort study (1992-2020) of 101 consecutive adult patients who underwent stereotactic biopsy, open biopsy, or resection for a newly diagnosed central nervous system lymphoma.The diagnostic yield was 100% despite preoperative steroid administration in 48/101 cases (47.5%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.006) was an independent predictor of a new postoperative focal neurological deficit (7/101 cases, 6.9%). A previous history of hematological malignancy (p = 0.049), age 65 years or more (p = 0.031), and new postoperative neurological deficit (p 0.001) were independent predictors of a Karnofsky Performance Status score decrease 20 points or more postoperatively (13/101 cases, 12.9%). A previous history of hematological malignancy (p = 0.034), and preoperative Karnofsky Performance Status score less than 70 (p = 0.024) were independent predictors of postoperative hemorrhage (13/101 cases, 12.9%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.019), and a previous history of hematological malignancy (p = 0.014) were independent predictors of death during hospital stay (8/101 cases, 7.9%). In the 82 immunocompetent patients harboring a primary central nervous system lymphoma, age 65 years or more (p = 0.044), and time to hematological treatment more than 21 days (p = 0.008), were independent predictors of a shorter overall survival. A dedicated hematological treatment (p 0.001) was an independent predictor of a longer overall survival.Brain biopsy is feasible with low morbidity for central nervous system lymphomas. Postoperatively, patients should be promptly referred for hematological treatment initiation.

Purpose The aim of this study was to evaluate the role of frailty required in the surgical risk assessment in old patients with IDH-wildtype glioblastoma on surgical outcome, overall survival, and functional dependency. Methods We reviewed records of old and frail patients surgical treated at our institution between January 2018 to May 2021. Inclusion criteria were : 1) neuropathological diagnosis of IDH-wildtype glioblastoma; 2) patient older than 65 years at the time of surgery; 3) available data to assess the frailty index according to the 5-mFI. Results A total of 47 patients were included. The 5-mFI was at 0 in 11 cases (23.4%), at 1 in 30 cases (63.83%), at 2 in 2 cases (4.25%), at 3 in 2 cases (4.25%), at 4 in 2 cases (4.25%). A GTR was performed in 26 patients (55.3%), a STR was performed in 13 patients (27.6%), and a B was performed in 8 patients (17.1%). The rate of 30-day postoperative complications was higher in B and in the 5-mFI = 4 subgroup (p > 0.05). GTR and age ≤ 70 years were independent predictors of a longer overall survival (p

This work deals with the investigation of alkaline binders obtained from binary mixtures of carbonate-rich illitic clay from deposits in southern Italy and two industrial by-products with very different total composition and calcium content, i.e., blast furnace slag and type F fly ash, respectively. To improve the reactivity, the selected clay was ground in a ball miller and heated to 700 °C. The binary mixtures were alkali activated with NaOH solution at 4 M and 8 M, and the activated pastes were cured at room temperature and relative humidity >90% in a climatic chamber. Heat flow, total heat and compressive strength (2, 7 and 28 days) were determined. The hardened pastes were characterized by X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX). Results show that the main reaction product in all samples is a gel or mixture of C-A-S-H/(N, C)-A-S-H type gel depending on the calcium content in the precursors. The paste, made up of a 1:1 weight proportion of carbonate-rich illitic clay and blast furnace slag, showed the formation of a more compact matrix than that observed in each individually activated component, achieving the considerable mechanical strength value of 45 MPa after 28 days, which suggests a very positive interaction between the two calcium-rich solid precursors. The binary mixture of carbonate-rich illitic clay and F fly ash showed relatively low compressive strength (below 15 MPa), which has been related to the poor reaction potential of fly ash regarding the alkali activation at room temperature. The modification of curing parameters is expected to improve the reaction of carbonate-rich illitic clay/fly ash blend. The clay activation method used in this study has been demonstrated to be suitable for larger scale industrial pre-treatment set-ups.

INTRODUCTION: Aggressive osteoblastoma (AO) represents a rare tumor with borderline features between benign osteoblastoma and osteosarcoma. Having a local aggressive behavior without metastasizing attitude, radical excision is a mainstay treatment. Conversely, spine fusion technique is still debated. We report a rare case of cervicothoracic junction (CTJ) AO and the tailored decision-making process to choose the best treatment. CASE PRESENTATION: A 34-year-old man complaining of neck pain was admitted to our department. Cervicothoracic MRI revealed a well-circumscribed lesion involving C7 left lamina with cortical erosion and mild spinal canal invasion. Additionally, STIR sequences exhibited a bright signal spreading through the posterior third of the C7 and T1 vertebrae which on T1-weighted and T2-weighted sequences appeared isointense and hyperintense, respectively. Therefore, the patient underwent a C7 laminotomy. Histology revealed an aggressive variant of osteoblastoma. Therefore, tumor was classified as AO and surgical management was reconsidered. A combined anterior and posterior approach was recommended to reach oncological radicality and spinal stability. At 6-years follow-up, patient remained neurologically intact without signs of recurrence and/or of instability. DISCUSSION: Due to its rarity and mimicking features, diagnosis of AO results challenging. Due to its aggressive behavior, radical surgery is the mainstay treatment. Conversely, the most suitable fusion technique is still debated. A proper surgical management should be focused on oncological radicality to guarantee the total tumoral removal avoiding progression or recurrences. Similarly, a proper evaluation of the long-term spinal balance should be assessed to avoid developing of spinal deformities or instrumentation failures.

Lymphedema can occur when tissue fluid cannot enter or leaks from the lymphatic system into surrounding tissues. Some genetic causes of primary lymphedema are known, but these currently explain a minority of cases. Previous studies have shown that dominant-negative mutations in angiopoietin 2 (ANGPT2), which is involved in lymphatic vessel formation and maturation, promote lymphangiogenesis in mice. Leppänen et al. now show that inactivating mutations in angiopoietin 2 associate with primary lymphedema in humans.Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain

Purpose: In search of novel strategies to improve the outcome of advanced prostate cancer, we considered that prostate cancer cells rearrange iron homeostasis, favoring iron uptake and proliferation. We exploited this adaptation by exposing prostate cancer preclinical models to high-dose iron to induce toxicity and disrupt adaptation to androgen starvation. Experimental Design: We analyzed markers of cell viability and mechanisms underlying iron toxicity in androgen receptor–positive VCaP and LNCaP, castration-resistant DU-145 and PC-3, and murine TRAMP-C2 cells treated with iron and/or the antiandrogen bicalutamide. We validated the results in vivo in VCaP and PC-3 xenografts and in TRAMP-C2 injected mice treated with iron and/or bicalutamide. Results: Iron was toxic for all prostate cancer cells. In particular, VCaP, LNCaP, and TRAMP-C2 were highly iron sensitive. Toxicity was mediated by oxidative stress, which primarily affected lipids, promoting ferroptosis. In highly sensitive cells, iron additionally caused protein damage. High-basal iron content and oxidative status defined high iron sensitivity. Bicalutamide–iron combination exacerbated oxidative damage and cell death, triggering protein oxidation also in poorly iron-sensitive DU-145 and PC-3 cells. In vivo, iron reduced tumor growth in TRAMP-C2 and VCaP mice. In PC-3 xenografts, bicalutamide–iron combination caused protein oxidation and successfully impaired tumor expansion while single compounds were ineffective. Macrophages influenced body iron distribution but did not limit the iron effect on tumor expansion. Conclusions: Our models allow us to dissect the direct iron effect on cancer cells. We demonstrate the proof of principle that iron toxicity inhibits prostate cancer cell proliferation, proposing a novel tool to strengthen antiandrogen treatment efficacy.

This article belongs to the Special Issue Low Binder Concrete and Mortars., The present study explores the effect of activating solution concentration (4, 6 and 8 M NaOH) on mechanically and thermally pre-treated carbonate-high illite clay (LCR). Pastes were prepared with an alkaline solution/clay (S/B) ratio of 0.55, which were cured at room temperature and relative humidity > 90% in a climatic chamber. At two and 28 days, compressive mechanical strength was determined, and the reaction products were characterised by X-ray Powder Diffraction analysis (XRPD), Fourier-transform infrared spectroscopy (FTIR) and Scanning Electron Microscopy - Energy Dispersive X-ray spectroscopy (SEM/EDX). Results obtained showed that the presence of reactive calcium in the starting clay induces co-precipitation of a mix of gels: An aluminium-enriched C-S-H gel (C-A-S-H) and a N-A-S-H gel, in which sodium is partially replaced by calcium (N,C)-A-S-H. Pastes prepared with higher (6 or 8 M) activator concentrations exhibit a more compact matrix than the ones prepared with 4 M NaOH. The findings show that the use of a 6 M NaOH solution yields a binder with two days compressive strength >20 MPa and 28 days strength of over 30 MPa., The research was also partially funded by the Spanish Ministry of the Economy, Industry and Competitiveness and ERDF under project BIA2016-76466-R.

The present study focuses on the assessment of the effects of different activation methods on carbonate-rich clays, to understand the mineralogical differences originated and to exploit such information to industry for traditional and innovative applications, especially as a precursor for alkali activated binders. Illite carbonate-rich clay samples were subjected to thermal activation in ox/red atmosphere between 400 and 900 °C, mechanical activation (grinding for 5, 10 and 15 min) and to a combination of such treatments. Mineralogical and textural changes in the activated samples were evaluated through X-ray powder diffraction, Fourier transform infrared spectroscopy and thermal techniques. The activated samples with the highest content of amorphous phase underwent leaching tests in a 3 M NaOH solution by means of inductively coupled plasma-mass spectrometry. The application of the three processing routines, yielded three types of activated clays with different leaching modes of Si, Al, K and Ca: (1) high energy grinding preferentially delaminates clay minerals and reduces the grain size of calcite. K leaching reaches the highest values; (2) thermal heating at 800 °C increases relatively the Si/Al solubility ratio, but the absolute concentrations of these elements are equal or lower than those obtained from ground clays. The relatively higher leaching of Ca is influenced by the formation of non-stoichiometric and poorly crystalline Ca-silicates and -aluminosilicates; (3) high energy grinding combined with heating treatment yields an extended amorphisation, mainly at the expense of clay minerals, with the highest leaching of Si and Al, and the lowest of Ca. New formed K-feldspars inhibit the concentration of K in alkaline solution.

Cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes has been revolutionizing medical oncology, and the clinical success of monoclonal antibodies targeting either cytotoxic T lymphocyte antigen-4 (CTLA-4) or program death-1 (PD-1) in patients affected by melanoma, Hodgkin's lymphoma, Merkel cell carcinoma, and head and neck, bladder, renal cell or non-small cell lung cancer is way beyond the most optimistic expectation. However, immune checkpoint blockade (ICB) has failed to arrest progression in a consistent amount of patients affected by those tumors, and various histological types, including breast, colon and prostate cancer, are less sensitive to this therapeutic approach. Such clinical findings have fueled massive research efforts in the attempt to identify pre-existing and acquired mechanisms of resistance to ICB. Here we focus on evidences emerging from studies in humans on how tumor cells and the tumor microenvironment contribute to the heterogeneous clinical responses, and we propose strategies stemming from pre-clinical models that might improve clinical outcomes for patients.

Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain30% of cases. Angiopoietin 1 (ANGPT1) and ANGPT2 function via the TIE1-TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and 2) receptor complex and α5β1 integrin to form an endothelial cell signaling pathway that is critical for blood and lymphatic vessel formation and remodeling during embryonic development, as well as for homeostasis of the mature vasculature. By screening a cohort of 543 individuals affected by primary lymphedema, we identified one heterozygous de novo

Can municipalities infringe Aboriginal or treaty rights without consulting the affected Indigenous group? In Neskonlith Indian Band v. Salmon Arm (City), the British Columbia Court of Appeal answered this question in the affirmative, finding that the city of Salmon Arm did not need to consult the Neskonlith First Nation about impacts from the construction of a shopping mall. In what was technically obiter dicta, the Court permitted the municipal project to proceed, and told the First Nation that its only recourse was to complain to the provincial government in a separate proceeding.

Objective An updated and comprehensive review on dysembryoplastic neuroepithelial tumor (DNET) focusing on differential diagnosis, atypical presentation, seizure outcome, and risk of malignant transformation. Methods A PubMed/MEDLINE-based literature search has been performed using “dysembryoplastic neuroepithelial tumor” as a keyword. Two treated cases characterized by an atypical presentation have been reviewed. Results Of 1162 articles, 200 relevant studies have been selected. DNET is a benign mixed neuronal-glial tumor causing drug-resistant epilepsy primarily in children and young adults. The typical radiological pattern is a magnetic resonance imaging (MRI) T1-hypointense, T2-, and fluid-attenuated inversion-recovery hyperintense multicystic lesion involving the cerebral cortex with no edema. Contrast enhancement may be present and a focal cortical dysplasia is commonly associated with it. MRI diffusion, perfusion, and spectroscopy have a paramount role in the differential diagnosis. The “specific glioneuronal elements” are pathognomonic. They are positive for S100 protein, synaptofisin, neuronal nuclei, oligodendrocyte transcription factor, neurite outgrowth inhibitor, and microtubule-associated protein 2, but negative for glial fibrillary acidic protein. As opposed to v-myb avian myeloblastosis viral oncogene homolog, isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutation and codeletion 1p-19q, fibroblast growth factor receptor 1 and BRAF V600E mutations are present. The effectiveness of surgery on seizure outcome has been established. Rare malignant transformations have been reported, especially in extra-temporal and complex forms. Conclusions Advanced MRI techniques are fundamental in the differential diagnosis for DNET versus other low-grade gliomas. Immuno-phenotype assessment and search for fibroblast growth factor receptor 1 and BRAF V600E mutations limit the risk of misdiagnoses. A gross total tumor removal is generally associated with a seizure-free outcome. Recurrences and malignant transformations may rarely follow, legitimizing MRI surveillance in cases of subtotal tumor resection.

Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR gene–engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission. Y-redirected T cells proved hyporesponsive in peripheral lymphoid organs, whereas they retained effector function at the tumor site, where in synergy with tumor-redirected lymphocytes, they instructed TNFα expression, endothelial cell activation, and intratumoral T-cell infiltration. While neutralizing TNFα hindered GVT effects by the combined T-cell infusion, a single injection of picogram amounts of NGR-TNF, a tumor vessel–targeted TNFα derivative currently in phase III clinical trials, substituted for Y-redirected cells and enabled tumor debulking by tumor-redirected lymphocytes. Together, our results provide new mechanistic insights into allogeneic GVT, validate the importance of targeting the tumor and its associated stroma, and prove the potency of a novel combined approach suitable for immediate clinical implementation. Cancer Res; 77(3); 658–71. ©2016 AACR.

Aim To identify the range of dimensional morphometric variability correlated to the basilar and condylar part of the occipital bone, which may affect the choice of approach to ventral intradural foramen magnum (FM) lesions. Material and methods In total, 25 dry skulls and 50 head computed tomography (CT) scan results have been assessed in detail, focusing on the FM, occipital condyles, jugular tubercles (JT), and hypoglossal canals (HC). A morphometric analysis has been carried out using linear and angular measurements to estimate the range of the dimensional variability of these structures. Data were presented as mean ± standard deviation, ranges, and interquartile range on a boxplot. The sagittal intercondylar angle (SICA) and anterior condylar angle (ACA) have been found to be important in estimating the axial orientation of the condyles, whereas the JT-HC interline ratio has indicated the prominence of the tubercles. Results The SICA and ACA have exhibited high variability. The average JT-HC interline ratio was 0.8. Wider SICA-ACA and higher JT-HC interline ratio make the posterolateral approach advantageous. An anterior medial or far-medial endoscopic route is indicated in opposite conditions. In this study, two illustrative cases have been reported. Conclusion A cautious preoperative morphometric evaluation of the FM region must be considered prior to using tailored and safe anterior endoscopic and posterolateral approaches to ventral intradural lesions to identify the advantages of a certain corridor as much as possible, thereby minimizing the risk of complications.

Objective To delineate the most recommendable treatment of spontaneous intracerebral hemorrhages and the indication for surgery, its timing, and the best surgical technique to be adopted case by case. Methods Based on PubMed/MEDLINE, Embase, and the Cochrane Library databases, a systematic review of the literature was performed using as keywords the terms "spontaneous intracerebral hemorrhage," "surgical management," "medical management," "supratentorial," and "infratentorial." Because of the highest level of evidence, only randomized and nonrandomized clinical trials, meta-analyses, and comparative cohort studies reported within the last 12 years were selected. An updated and evidence-based treatment algorithm was reported also. Results The search initially returned 255 articles. After application of the exclusion criteria, only 19 studies were selected. According to the site and volume of the hematoma, admission Glasgow Coma Scale (GCS) score, and progressive neurologic decline, specific subgroups were identified. Surgery must be considered in patients with an admission GCS score ranging between 5 and 12 and a hematoma volume >30 mL. The best time-window has been reported to be 7–24 hours after ictus. Endoscopic surgery is recommendable for patients with a supratentorial hematoma >60 mL and with a poor GCS score (4–8). Alternative techniques, such as minimally invasive puncture and thrombolysis, may be considered for deeper hematoma. Conclusions Careful selection of patients eligible for surgery is mandatory. The optimal timing falls into a time-window ranging between 7 and 24 hours after ictus. Minimal invasive techniques are valuable surgical options for patients in a poor GCS score or harboring large deep-seated hemorrhages.

Prostate adenocarcinoma (PCa) and melanoma are paradigmatic examples of tumors that are either poorly or highly sensitive to therapies based on monoclonal antibodies directed against regulatory pathways in T lymphocytes [i.e., immune checkpoint blockade (ICB)]. Yet, approximately 40% of melanoma patients are resistant or acquire resistance to ICB. What characterize the microenvironment of PCa and ICB-resistant melanoma are a scanty cytotoxic T cell infiltrate and a strong immune suppression, respectively. Here, we compare the tumor microenvironment in these two subgroups of cancer patients, focusing on some among the most represented immune checkpoint molecules: cytotoxic T lymphocyte-associated antigen-4, programmed death-1, lymphocyte activation gene-3, and T cell immunoglobulin and mucin-domain containing-3. We also report on several examples of crosstalk between cancer and immune cells that are mediated by inhibitory immune checkpoints and identify promising strategies aimed at overcoming ICB resistance both in PCa and melanoma.

Purpose: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTL). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intratumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors. Experimental Design: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with autochthonous prostate cancer and C57BL/6 mice with orthotopic B16 melanoma were treated with NGR-TNF, adoptive T-cell therapy (ACT), and ICB, and monitored for immune surveillance and disease progression. Results: The combination of ACT, NGR-TNF, and ICB was the most effective in delaying disease progression, and in improving overall survival of mice bearing ICB-resistant prostate cancer or melanoma. Mechanistically, the therapeutic effects were associated with potent tumor infiltration, especially by endogenous but also by adoptively transferred PD-1+, granzyme B+, and interferon-γ+ CTLs. The therapeutic effects were also associated with favorable T-effector/regulatory T cell ratios. Conclusions: Targeting the tumor vasculature with low-dose TNF in association with ACT may represent a novel strategy for enhancing T-cell infiltration in tumors and overcoming resistance to immune checkpoint blockers. Clin Cancer Res; 24(9); 2171–81. ©2018 AACR.

A modelling approach for the analysis of preferences data is proposed in order to represent the liking behaviour and the uncertainty of the consumers, and to explain the role that the consumers' covariates (e.g. gender, age, occupation, etc.) play in the assessment of the preferences. The main evidence obtained from the Eurosalmon project data set is discussed, focussing on the most relevant features of the approach, even with reference to sensory characteristics. Some generalizations and further lines of research are also proposed. © 2007 Elsevier Ltd. All rights reserved.

A statistical model for ranks is presented, and some results on its parameter are discussed. In particular, maximum likelihood inference is developed, with and without covariates; thus, a statistical model for rank data is introduced in order to link the expressed ranks to the main features of the raters. Some empirical evidence from a marketing survey confirms the usefulness of the proposal in the study of the preferences.

A variance components model with response variable depending on both fixed effects of explanatory variables and random components is specified to model longitudinal circular data, in order to study the directional behaviour of small animals, as insects, crustaceans, amphipods, etc. Unknown parameter estimators are obtained using a simulated maximum likelihood approach. Issues concerning log-likelihood variability and the related problems in the optimization algorithm are also addressed. The procedure is applied to the analysis of directional choices under full natural conditions ofTalitrus saltator from Castiglione della Pescaia (Italy) beaches.

This study compared the influence of different methods of preimpression preparation on the quality of occlusal reproduction in irreversible hydrocolloid impressions. A total of 30 impressions of the lower dental arch of a patient were made with five different preimpression preparation procedures. Stone casts were made and analyzed. Critical comparison showed that the preimpression preparation influenced the quality of the occlusal surface of the cast. Fingerpainting the occlusal surface with fluid hydrocolloid before positioning the loaded impression tray, associated with use of a saliva ejector, reduced the incidence of macroscopic defects on the occlusal surface of the impressions.

Vehicle emissions represent an increasing contributor to air pollution in urban and country areas which gives rise to a range of environmental problems related to air quality. This has led to increasingly stringent regulatory laws on exhaust emissions level and composition. The US regulations, signed in Dec. 2000, set new standards for measurement of automotive exhaust emissions. The emission limits for regulated species, such as carbon oxides (CO and CO2), hydrocarbons (THC), and nitrogen oxides, i.e. NO, NO2, N2O (referred as NOx), are being reduced, and new components such as methanol and formaldehyde are being added to the list of monitored species. In Japan, diesel emission standards require that in-use onroad light commercial vehicles should meet NOx emission of 0.25 g/km starting from the end of 2005 and achieve full implementation by 2011 (Nakamura et al., 2006). The European Commission has also introduced a series of regulations, the so called EURO Emission directives, from Euro I in 1991 to tighter limitations in 2009 (Euro V 80 g/km) and 2014 (Euro VI 0.08 g/Km), to meet the air quality standards stated by the international agencies (van Asselt & Biermann, 2007). The standard and validated on-line technologies for regulated emissions are effective at monitoring few components, but are limited in their use for measuring other gases. Single-wavelength non-dispersive infrared filters for CO and CO2 monitoring cannot be used for other species due to interferences from water and other molecules. Chemiluminescence analyzers, which traditionally are used to measure NOx compounds, cannot differentiate NO from NO2 in the same test, nor identify the other NOx gases. Flame ionization detectors cannot differentiate individual hydrocarbons. To measure raw exhaust, each technique requires a cold trap for water vapour, which can affect the concentrations of other gases. In addition, calibrations are necessary for each analysis, avoiding on-line and real-time emission monitoring. To sample other gases in the exhaust, bag samples must be collected and taken to a laboratory for further analysis. Expensive dilution equipment must be used to prevent water condensation in the bag. Each bag sample gathers exhaust for several minutes, therefore the final result of the test is an integrated average of the gas concentrations and all time resolution is lost. Methanol and formaldehyde samples are collected with impingers, which dissolve the gases by passing them through a water-based solution. The extract is then analyzed using high-performance liquid chromatography (HPLC). Gas chromatography

Several spectroscopic methods based on mid-infrared quantum cascade lasers for the ultrasensitive detection of nitric oxide have been developed with detection limit in ppbv and sub-ppbv range. We will describe here a selection of the most effective techniques, i.e., laser absorption spectroscopy, cavity-enhanced spectroscopy, photoacoustic spectroscopy, and Faraday modulation spectroscopy. For each technique, advantages and drawbacks will be underlined.

We will report on the design and realization of optoacoustic sensors based on commercial quantum cascade lasers for environmental analysis applications. Different configurations will be described: i) sensors based on resonant photoacoustic cells, a "standard" H cell and an innovative T-cell; ii) sensor based on quartz enhanced photoacoustic spectroscopy. We will analyze the results obtained in the detection of nitric oxide.

We will report here on the design and realization of an optoacoustic sensor for the detection of formaldehyde. The sensor consists of a commercial QCL and a resonant PA cell. Two different cell configurations have been investigated: a "standard" H cell and an innovative T-cell with an optical fiber directly inserted into. Two different type of sound detector have been employed: electret microphones and optical MEMS-based microphone. As possible applications, we will describe the results obtained in the detection of formaldehyde (CH(2)O), a gas of great interest for industrial processes and environmental monitoring.

The detection and quantification of trace gases is of great interest in a wide range of applications such as environmental monitoring, industrial process control and medical diagnostics. In combination with quantum cascade lasers, photoacoustic spectroscopy offers the advantage of high sensitivity (parts per billion detection limits), compact set-up, fast time-response and simple optical alignment. We will report here on the design and fabrication of optoacoustic sensors based on two different cell configurations to detect nitric oxide and formaldehyde.

We report on the realization of an optoacoustic sensor based on mid-infrared quantum-cascade lasers (QCLs) for the detection of nitric oxide (NO) and formaldehyde (CH(2)O). A resonant photoacoustic cell equipped with 4 electret microphones was excited in its first longitudinal mode by the modulated laser light. A detection limit of 150 parts in 10(9) (ppbv) for NO and CH(2)O was found, using distributed feedback QCLs operating in pulsed mode at 5.34 mu m and 5.62 mu m, respectively.

We report on the realization of a optoacoustic sensor based on mid-infrared quantum-cascade lasers (QCLs) for the detection of nitric oxide (NO) and formaldehyde (CH(2)O). A resonant photoacoustic cell equipped with 4 electret microphones was excited in its first longitudinal mode by the modulated laser light. A detection limit for of 300 parts in 10(9) (ppbv) for NO and 150 ppbv for CH(2)O is found, using distributed feedback QCLs operating in pulsed mode at 5.34 mu m and 5.6 mu m, respectively.

This paper presents a discrete mixture model as a suitable approach for the analysis of chronic pain data, when they are expressed by means of ordered scores (ratings). The model is developed to allow for covariates effects; parameters estimation by maximum likelihood (using an E—M algorithm) and related inferential issues are discussed. A case-study concerning the assessment of pain (for a given pathology) and the effect of patients' covariates (e.g., gender, depression state) is illustrated. Besides, the same covariates are considered also for explaining the disruption in everyday lifestyle due to the chronic pain condition.

The use of photoacoustic spectroscopy and mid-infrared quantum-cascade lasers (QCLs) for the detection of hexamethyldisilazane (HMDS) is reported. A detection limit of 200 parts in 10(9) is found using a Fabry-Perot QCL operated at 8.4 mu m in pulsed mode and a photoacoustic cell equipped with four electret microphones. The laser multimode spectrum matches the range of the N-H bending absorption band of HMDS. Further improvements to reach lower detection limits are discussed. (c) 2005 Elsevier B.V. All rights reserved.

A photoacoustic trace-gas sensor for the measurement of nitric oxide with a detection limit of 500 parts in 10(9) has been demonstrated. The radiation source was a thermoelectrically cooled distributed-feedback quantum-cascade laser operating in pulsed mode near 5.3 microm with an average laser power of 8 mW. A resonant photoacoustic cell was excited in its first longitudinal mode by the modulated laser light. Preliminary measurements have been performed to test the performance of our photoacoustic sensor; possible improvements to reach lower detection limits are discussed.

In this paper we study the interaction between the estimation of the fractional differencing parameter d of ARFIMA models and the common practice of instantaneous transformation of the observed time series. At this aim, we first discuss the effect of a nonlinear transformation of the data on the identification of the process and on the estimate of d. Thus, we propose a joint estimation of the Box-Cox parameter and d by means of a modified normalized version of the Whittle likelihood. Then, the variance and covariance matrix of the parameters estimates is obtained. Finally, a Monte Carlo study is performed in order to check the behaviour of the proposed estimators in finite samples. © Springer-Verlag 2003.