An improved balanced replicated sampling design for preliminary screening of the tailings ponds aiming at zero-waste valorization. A Romanian case study.

The scope of this study consists of setting up of an integrated cost-effective sampling & laboratory analyses procedure which delineates sampling, sub-sampling and analytical uncertainties in case of fine-grained extractive waste deposits. This procedure is designed to support the decision makers towards fine-grained waste deposits upcycling and land reclamation. This procedure consists of a balanced replicated sampling design (BRSD) coupled with a three split levels ANOVA data processing. The paper provides the readership with the mathematical backgrounds of the three split level ANOVA analysis (3L-ANOVA) and an Excel algorithm for its implementation. Also, the paper presents an example of implementation of the developed methods in the case of a Romanian iron ore tailings (IOT) old pond. The findings of the paper consist of: a) argues, based on OM, SEM-EDS, XRFS and XRD observations, that classical TOS is ineffective for fine-grained waste deposits; b) BRSD in conjunction with 3L-ANOVA analysis is the only approach fit for reliable characterization of the fine-grained stockpiles; c) sampling uncertainty is the critical factor of the uncertainty budget of the analyte concentration; d) Lilliefors approach is adequate for the hypothesis testing where or not the measurand is normal distributed; e) The outcomes of the BRDSD&3L-ANOVA investigations carried on Teliuc tailings, estimated at circa 5.5* 106 m3, consist mainly of mineral quantification at lot level i.e. quartz ∼54% (±7%), hematite ∼15% (±3%), calcite ∼11% (±3%), MgO 3% (±1%), Al2O3 9% (±2%). The concentrations of some CRMs like Ti, V, Ba, Y, W were found at ACE limits and their associated relative expanded uncertainties overpass 50%. Thus, the expanded uncertainties clearly depict the reliability of acquired data for the decision makers regarding waste valorization. f) The IOT into Teliuc can be upcycled as minerals for cement and ceramic industries as well as for geopolymer manufacture. Also, IOT can be downcycles as filler in road construction and mine closure. Finally, the Teliuc yard can be rehabilitated with zero-waste left behind. The data exactness provided by this procedure can be increased to any desirable level through increasing the number of collected items, but the cost of sampling and analyses increases proportionally. In such circumstances, the posted approach can be tailored at the stakeholder request as to safely underpin the decision to turn finegrained by-products into valuable secondary resources, facilitating a greater circularity of the mining industry.

A Morphological and Immunohistochemical Study of the Tumoral and Inflammatory Cells in Pancreatic Ductal Adenocarcinoma.

This study is aimed at investigating tumoral and inflammatory cells and the significance of the prognostic factors of pancreatic ductal adenocarcinoma (PDAC); it is also aimed at determining the role of immunohistochemistry in the diagnosis and prognosis of this neoplasm. Materials and Methods. 230 cases of pancreatic ductal adenocarcinoma were included in the study group; these cases were selected from the archives of the Department of Pathology of the Fundeni Clinical Institute over a ten-year period. Immunohistochemistry was performed using the following antibodies: MUC 1, CD 34, Factor VIII, CD 68, MMP-7, CEA, p21, p53, and Ki 67. Results. There were 133 male (57.8%) and 97 female (42.2%) patients included in this study, with ages between 20 and 81 years old (mean age: 58.2 years) and with tumors located in the pancreatic head (n = 196; 85.2%), pancreatic body (n = 12; 5.2%), and pancreatic tail (n = 20, 8.7%), as well as panpancreatic tumors (n = 2; 0.9%). Patients presented with early stages (IA and IB), with low pathologic grade (G1), with small size tumors (less than 1-1.5 cm), with tumors located in the head of the pancreas, (p53: negative; p21: positive; and CD 68: positive in peritumoral tissue), with low nuclear index (Ki 67 < 10%), without metastases at the time of surgery (had a better prognosis), and with a survival rate of about 7 months. Conclusions. Immunohistochemistry is useful for an accurate diagnosis, differential diagnosis, and establishment of additional factors that might have a prognostic importance. It is recommended to study peritumoral tissue from the quantitative and qualitative points of view to increase the number of prognostic factors. This study represents a multidisciplinary approach, and it is a result of teamwork; it presents histopathological methods of examination of this severe illness and describes only a part of the scientific effort to determine the main pathological mechanisms of this neoplasm.

Multimodal nocturnal seizure detection in a residential care setting: A long-term prospective trial.

OBJECTIVE: To develop and prospectively evaluate a method of epileptic seizure detection combining heart rate and movement. METHODS: In this multicenter, in-home, prospective, video-controlled cohort study, nocturnal seizures were detected by heart rate (photoplethysmography) or movement (3-D accelerometry) in persons with epilepsy and intellectual disability. Participants with >1 monthly major seizure wore a bracelet (Nightwatch) on the upper arm at night for 2 to 3 months. Major seizures were tonic-clonic, generalized tonic >30 seconds, hyperkinetic, or others, including clusters (>30 minutes) of short myoclonic/tonic seizures. The video of all events (alarms, nurse diaries) and 10% completely screened nights were reviewed to classify major (needing an alarm), minor (needing no alarm), or no seizure. Reliability was tested by interobserver agreement. We determined device performance, compared it to a bed sensor (Emfit), and evaluated the caregivers' user experience. RESULTS: Twenty-eight of 34 admitted participants (1,826 nights, 809 major seizures) completed the study. Interobserver agreement (major/no major seizures) was 0.77 (95% confidence interval [CI] 0.65-0.89). Median sensitivity per participant amounted to 86% (95% CI 77%-93%); the false-negative alarm rate was 0.03 per night (95% CI 0.01-0.05); and the positive predictive value was 49% (95% CI 33%-64%). The multimodal sensor showed a better sensitivity than the bed sensor (n = 14, median difference 58%, 95% CI 39%-80%, p < 0.001). The caregivers' questionnaire (n = 33) indicated good sensor acceptance and usability according to 28 and 27 participants, respectively. CONCLUSION: Combining heart rate and movement resulted in reliable detection of a broad range of nocturnal seizures.

An Attempt to Build a National Prospective Electronic Database for Pancreaticoduodenectomies in Romania - Preliminary Results of the First Year Enrollment.

Introduction: National databases for pancreaticoduodenectomies (PD) have contributed to better postoperative outcomes after such complex surgical procedure because the multicentre collection of data allowed more reliable analyses with quality assessment and further improvement of technical issues and perioperative management. The current practice and outcomes after PD are poorly known in Romania because there was no national database for these patients. Thus, in 2016 a national-intent electronic registry for PD was proposed for all Romanian surgical centers. The study aims to present the preliminary results of this national-intent registry for PD after one-year enrollment. Patients Methods: The database was started on October 1st, 2016. Data were prospectively collected with an electronic online form including 102 items for each patient. The registry was opened to all the Departments of Surgery from Romania performing PD, with no restriction. Results: During the first year of enrollment were collected the data of 181 patients with PD performed by 24 surgeons from four surgical centers. The age of patients was 64 years (28 - 81 years), with slightly male predominance (61.3%). Computed tomography was the main preoperative imaging investigation (84.5%). All the PDs were performed by an open approach. The Whipple technique was used in 53% of patients, and a venous resection was required in 14.3% of cases. A posterior approach PD was considered in 16.6% of patients. The stomach was used to treat the distal remnant pancreas in 50.1% of patients. The operative time was 285 min (110 - 615 min), and the estimated blood loss was 400 ml (80 - 3000 ml). The overall morbidity rate was 55.8%, with severe (i.e., grade III-IV Dindo-Clavien) morbidity rate of 10%, and 3.9% in-hospital mortality rate. The overall pancreatic fistula, delayed gastric emptying and hemorrhage rates were 19.9%, 39.8% and 15.5%. Periampullary malignancies were the main indications for PD (78.9%), with pancreatic cancer on the top (48%). Conclusions: To build a prospective electronic online database for PD in Romania appears to be a feasible project and a useful tool to know the current practice and outcomes after PD in our country. However, improvements are still required to encourage a larger number of surgical centers to introduce the data of patients with PD.

Multimodal, automated detection of nocturnal motor seizures at home: Is a reliable seizure detector feasible?

Objective: Automated seizure detection and alarming could improve quality of life and potentially prevent sudden, unexpected death in patients with severe epilepsy. As currently available systems focus on tonic-clonic seizures, we want to detect a broader range of seizure types, including tonic, hypermotor, and clusters of seizures. Methods: In this multicenter, prospective cohort study, the nonelectroencephalographic (non-EEG) signals heart rate and accelerometry were measured during the night in patients undergoing a diagnostic video-EEG examination. Based on clinical video-EEG data, seizures were classified and categorized as clinically urgent or not. Seizures included for analysis were tonic, tonic-clonic, hypermotor, and clusters of short myoclonic/tonic seizures. Features reflecting physiological changes in heart rate and movement were extracted. Detection algorithms were developed based on stepwise fulfillment of conditions during increases in either feature. A training set was used for development of algorithms, and an independent test set was used for assessing performance. Results: Ninety-five patients were included, but due to sensor failures, data from only 43 (of whom 23 patients had 86 seizures, representing 402 h of data) could be used for analysis. The algorithms yield acceptable sensitivities, especially for clinically urgent seizures (sensitivity = 71-87%), but produce high false alarm rates (2.3-5.7 per night, positive predictive value = 25-43%). There was a large variation in the number of false alarms per patient. Significance: It seems feasible to develop a detector with high sensitivity, but false alarm rates are too high for use in clinical practice. For further optimization, personalization of algorithms may be necessary.

Assessment of sites of marrow and extramedullary hematopoiesis by hybrid imaging in primary myelofibrosis patients.

We investigated noninvasive procedures by hybrid imaging to assess the sites of active or inactive hematopoiesis in patients with primary myelofibrosis (PMF). To this end, we used two radionuclides, technetium 99m ((99m) Tc) and indium 111-chloride ((111) In-Cl3 ), coupled with single-photon emission tomography/computed tomography (SPECT/CT). We studied five patients with PMF and one with secondary myelofibrosis (MF). The classical pattern of lower fixation of both tracers at the axial skeleton where the myelofibrotic process occurs and the reactivation of sites of active hematopoiesis at the distal skeleton were confirmed. Coupling both radionuclides to SPECT/CT imaging allowed for more precise visualization of the sites of extramedullary hematopoiesis as those observed in the spleen and liver. Splenic high uptake of (111) In-Cl3 coupled with SPECT/CT represents a pathognomonic feature of PMF. We conclude that, the hybrid imaging procedures that we studied might constitute an alternative noninvasive method for the screening of the whole-body marrow and, by this way, to assess the impact of targeted therapies in PMF patients in whom it is well known that the distribution of the hematopoietic active areas is disturbed. Hybrid imaging could also be useful for diagnostic purposes in cases of early PMF or in suspected cases of myelofibrosis secondary to polycythemia vera or essential thrombocythemia.

Asymmetric and Diffuse Uptake of Left Femur in a 3-Year-Old Child Bone Scan: An Unusual Aspect in Acute Lymphoblastic Leukemia.

Acute leukemia is a severe disease frequently encountered in childhood, often diagnosed in later stages because of nonspecific symptoms. It is known to produce uptake in bone scan, and previously described patterns have shown symmetrical abnormalities. However, we report the unusual aspect of the bone scan in a 3-year-old child who was referred to explore an isolated pain of his lower left limb, with hyperthermia and markers of inflammation. A bone scan showed an intense, asymmetrical uptake of the entire left femur. A few days later, his blood count showed circulating blast cells, leading to the diagnosis of leukemia.

Using photoplethysmography in heart rate monitoring of patients with epilepsy.

Heart rate is a useful neurophysiological sign when monitoring seizures in patients with epilepsy. In an ambulatory setting, heart rate is measured with ECG involving electrodes on the skin. This method is uncomfortable which is burdensome for patients and is sensitive to motion artifacts, which decrease the usability of measurements. In this study, green light photoplethysmography, an optical technique arising from the fitness industry, was evaluated for usefulness in a medical setting. Simultaneous overnight measurements of HR with a commercially available optical heart rate (OHR) sensor and with ECG (HRECG) were performed in 7 patients with epilepsy. Overall, there was no significant difference between OHR and HRECG in random 10-minute periods during wakefulness (p=0.69) and sleep (p=1.00). The Bland-Altman analysis showed negligible mean differences. Limits of agreement were higher during wakefulness and during the occurrence of two seizures possibly because of less reliable HRECG measurements due to motion artifacts. Optical heart rate seems less sensitive to these motion artifacts, and measurements are more user-friendly. The optical heart rate sensor may fill the gap of systems for ambulatory heart rate monitoring and can be especially useful in the context of seizure detection in patients with epilepsy.

Recording system and data fusion algorithm for enhancing the estimation of the respiratory rate from photoplethysmogram.

The respiratory rate is a vital parameter that can provide valuable information about the health condition of a patient. The extraction of respiratory information from photoplethysmographic signal (PPG) was actually encouraged by the reported results, our main goal being to obtain accurate respiratory rate estimation from the PPG signal. We developed a fusion algorithm that identifies the best derived respiratory signals, from which is possible to extract the respiratory rate; based on these, a global respiratory rate is computed using the proposed fusion algorithm. The algorithm is qualitatively tested on real PPG signals recorded by an acquisition system we implemented, using a reflection pulse oximeter sensor. Its performance is also statistically evaluated using benchmark dataset publically available from CapnoBase.Org.

Granulosa cell tumor of the ovary with high FDG uptake.

Granulosa cell tumor (GCT) of the ovary is a rare tumor accounting for 2%-5% of ovarian malignancies. Although the usefulness of 18F-FDG PET/CT is well demonstrated in the staging and follow-up of the great majority of ovarian cancers, GCTs are known to cause false-negative results on FDG PET because of very low FDG avidity. We present a case of a GCT in which an 18F-FDG PET/CT proved very useful in the detection of recurrence.

18F-fluoride PET/CT aspect of an unusual case of Erdheim-Chester disease with histologic features of Langerhans cell histiocytosis.

We report the case of a 63-year-old woman with Erdheim-Chester disease (ECD) and histologic features of Langerhans cell histiocytosis, both extremely rare histiocytic proliferations responsible of skeletal and extraskeletal involvement. 18F-Fluoride PET/CT revealed multiple intense focal uptake scattered throughout the skeleton. We also performed an 18F-FDG PET/CT which point out visceral and vascular involvement. This case illustrates the interest of PET/CT in ECD, a rare polymorphus and systemic disease, and in our knowledge, this is the first reported illustration of 18F-fluoride PET/CT findings in this pathology.

The 'nanobig rod' class of gold nanorods: optimized dimensions for improved in vivo therapeutic and imaging efficacy.

Currently, gold nanorods can be synthesized in a wide range of sizes. However, for the intended biological applications gold nanorods with approximate dimensions 50 nm × 15 nm are used. We investigate by computer simulation the effect of particle dimensions on the optical and thermal properties in the context of the specific applications of photoacoustic imaging. In addition we discuss the influence of particle size in overcoming the following biophysical barriers when administrated in vivo: extravasation, avoidance of uptake by organs of the reticuloendothelial system, penetration through the interstitium, binding capability and uptake by the target cells. Although more complex biological influences can be introduced in future analysis, the present work illustrates that larger gold nanorods, designated by us as 'nanobig rods', may perform better at meeting the requirements for successful in vivo applications compared to their smaller counterparts, which are conventionally used.

Gold nanorods as molecular contrast agents in photoacoustic imaging: the promises and the caveats.

Rod-shaped gold nanoparticles exhibit intense and narrow absorption peaks for light in the far-red and near-infrared wavelength regions, owing to the excitation of longitudinal plasmons. Light absorption is followed predominantly by non radiative de-excitation, and the released heat and subsequent temperature rise cause strong photoacoustic (optoacoustic) signals to be produced. This feature combined with the relative inertness of gold, and its favorable surface chemistry, which permits affinity biomolecule coupling, has seen gold nanorods (AuNR) attracting much attention as contrast agents and molecular probes for photoacoustic imaging. In this article we provide an short overview of the current status of the use of AuNR in molecular imaging using photoacoustics. We further examine the state of the art in various chemical, physical and biochemical phenomena that have implications for the future photoacoustic applications of these particles. We cover the route through fine-tuning of AuNR synthetic procedures, toxicity reduction by appropriate coatings, in vitro cellular interactions of AuNRs, attachment of targeting antibodies, in vivo fate of the particles and the effects of certain light interactions with the AuNR.

Light interactions with gold nanorods and cells: implications for photothermal nanotherapeutics.

Gold nanorods (AuNR) can be tailored to possess an intense and narrow longitudinal plasmon (LP) absorption peak in the far-red to near-infrared wavelength region, where tissue is relatively transparent to light. This makes AuNRs excellent candidates as contrast agents for photoacoustic imaging, and as photothermal therapeutic agents. The favorable optical properties of AuNR which depend on the physical parameters of shape, size and plasmonic coupling effects, are required to be stable during use. We investigate the changes that are likely to occur in these physical parameters in the setting of photothermal therapeutics, and the influence that these changes have on the optical properties and the capacity to achieve target cell death. To this end we study 3 sets of interactions: pulsed light with AuNR, AuNR with cells, and pulsed light with cells incubated with AuNR. In the first situation we ascertain the threshold value of fluence required for photothermal melting or reshaping of AuNR to shorter AuNR or nanospheres, which results in drastic changes in optical properties. In the second situation when cells are exposed to antibody-conjugated AuNR, we observe using transmission electron microscopy (TEM) that the particles are closely packed and clustered inside vesicles in the cells. Using dark-field microscopy we show that plasmonic interactions between AuNRs in this situation causes blue-shifting of the LP absorption peak. As a consequence, no direct lethal damage to cells can be inflicted by laser irradiation at the LP peak. On the other hand, using irradiation at the transverse peak (TP) wavelength in the green, at comparative fluences, extensive cell death can be achieved. We attribute this behavior on the one hand to the photoreshaping of AuNR into spheres and on the other hand to clustering of AuNR inside cells. Both effects create sufficiently high optical absorption at 532 nm, which otherwise would have been present at the LP peak. We discuss implications of these finding on the application of these particles in biomedicine.

Differential pathlength spectroscopy for the quantitation of optical properties of gold nanoparticles.

An accurate estimation of optical absorption coefficient (microabs) and scattering coefficient (microsca) is important in characterizing nanoparticles for identifying or optimizing applications such as photothermal therapy and photoacoustic imaging. In this exciting period where several fascinating methods have been unveiled for the synthesis of various nanoparticles, the field is still lacking in the availability of efficient characterization methods. We introduce an accurate and simple methodology to optically characterize nanoparticles which could fill the gap. This is based on differential pathlength spectroscopy (DPS), a dual optical fiber approach, originally developed to detect cancer endoscopically by measuring the optical properties of tissue in small interrogation volumes. We expand its use to nanoparticles in a method that allows us to resolve the effects of microabs and microsca in the extinction coefficient of low concentration samples. We outline the measurement protocol using the DPS system and describe the analysis of the data taking additional inputs from electron microscopy and discrete dipole approximation (DDA) simulations. The DPS signal from the sample is first translated into the backscattering coefficient using a calibration constant. Further, the backscattering coefficient is converted via the simulated scattering phase function into the scattering coefficient. With this knowledge and extinction coefficient measured using a conventional photospectrometer, the absorption coefficient is calculated. We prove the validity of the method using spherical and rod-shaped gold nanoparticles, comparing the results with outputs from DDA simulations. We also briefly touch upon the dilemma of the choice of the appropriate dielectric function for gold at the nanoscale.

Iodide impurities in hexadecyltrimethylammonium bromide (CTAB) products: lot-lot variations and influence on gold nanorod synthesis.

Recent reports [Smith and Korgel Langmuir 2008, 24, 644-649 and Smith et al. Langmuir 2009, 25, 9518-9524] have implicated certain hexadecyltrimethylammonium bromide (CTAB) products with iodide impurities, in the failure of a seed-mediated, silver and surfactant-assisted growth protocol, to produce gold nanorods. We used two of the three "suspect" CTAB products and a "good" CTAB product in the protocol, varying silver nitrate solutions in the growth solutions. We obtained excellent gold nanorod samples as witnessed in signature longitudinal plasmon peaks in optical extinction spectra, which we substantiated using electron microscopy. Analysis of these samples using inductively coupled plasma mass spectroscopy (ICP-MS) failed to detect iodide. We subsequently learnt from discussions with Smith et al. that different lot numbers within the same product had been analyzed by our respective laboratories. We can conclude that iodide impurities can vary significantly from lot to lot within a product, to such an extent that there is no guarantee that gold nanorods can be synthesized with one or other CTAB product. Conversely, labeling a CTAB product, identified by a product number or supplier name, as one whose use precludes the formation of nanorods, is also hasty.

Synthesis and bioconjugation of gold nanoparticles as potential molecular probes for light-based imaging techniques.

We have synthesized and characterized gold nanoparticles (spheres and rods) with optical extinction bands within the "optical imaging window." The intense plasmon resonant driven absorption and scattering peaks of these nanoparticles make them suitable as contrast agents for optical imaging techniques. Further, we have conjugated these gold nanoparticles to a mouse monoclonal antibody specific to HER2 overexpressing SKBR3 breast carcinoma cells. The bioconjugation protocol uses noncovalent modes of binding based on a combination of electrostatic and hydrophobic interactions of the antibody and the gold surface. We discuss various aspects of the synthesis and bioconjugation protocols and the characterization results of the functionalized nanoparticles. Some proposed applications of these potential molecular probes in the field of biomedical imaging are also discussed.