Analogue micropower FET techniques review

A detailed introduction to published analogue circuit design techniques using Si and Si/SiGe FET devices for very low-power applications is presented in this review. The topics discussed include sub-threshold operation in FET devices, micro-current mirrors and cascode techniques, voltage level-shifting and class-AB operation, the bulk-drive approach, the floating-gate method, micropower transconductance-capacitance and log-domain filters and strained-channel FET technologies

Nanoparticles for intestinal sepsis prevention synthesized via inverse miniemulsion polymerization

Previous research has shown that phosphate becomes depleted in the intestinal mucosa following local surgical injury or disease, triggering bacterial virulence and sepsis. Consequently, replenishment of depleted phosphate levels has been shown to prevent bacterial virulence in vitro[3] and sepsis in vivo[1]. Inverse phase miniemulsion polymerization (IPMP) has been extensively used in recent years in the production of nanocapsules for drug delivery of water-soluble therapeutic compounds that can be rendered degradable with time while allowing for sustained release of the encapsulated agent. In previous work we have successfully encapsulated inorganic phosphate salts, such as potassium monophosphate[2], into nanoparticles formed using IPMP. Our in vitro studies, however, have shown that polyphosphate salts, specifically sodium hexametaphosphate (PPi), are more effective at suppressing bacterial virulence[3]. This study focuses on the production and encapsulation of sodium hexametaphosphate into nanoparticles for controlled and extended release. Previous studies demonstrated[3] that encapsulation of sodium hexametaphosphate presents a series of challenges affecting the reproducibility of the IPMP process. Sodium hexametaphosphate is a strong lipophobe whose presence induces a high degree of order for water molecules. This modification in water structure weakens the surfactant interaction with water molecules, actively affecting the stability of the emulsion. This process, known as “salting-out”, has been shown to shift the hydrophilic-lipophilic balance (HLB) of nonionic surfactants towards a more lipophilic value[4]. While this issue has been addressed in a variety of previous studies, no mathematical correlation currently exists describing the effect of salt concentration on the HLB of a specific surfactant. Since miniemulsions require combinations of different phase-soluble surfactants, this adds to the complexity in predicting the extent and strength of the electrolyte effect on the stability of the emulsion system. In this study, we adjusted the IPMP process to counter the unstabilizing force created by the presence of sodium hexametaphosphate in the aqueous phase of the system. A precursor solution containing PEG diacrylate (PEGDA) macromer and NVP comonomer were chosen to create the hydrogel matrix, due to its biocompatibility and the ability to control the crosslinking density. The emulsion was formed of water in cyclohexane with the help of two nonionic surfactants, Tween 20 and SPAN 80. The effect of variations in HLB ranging from 4.0 to 9.5 on emulsion droplet size was investigated, for which the optimum overall HLB occurred at 6.5, an increase of two HLB points over the theoretical required value without salt interference[2, 3]. The effects of total surfactant amounts, reaction time, temperature and initiator concentration on nanoparticle yield were also explored. A final emulsion with 3.2% w/v of surfactants, 2 hours of reaction time, 64ºC and an initiator concentration equal to 1% of the initial double concentration resulted in a maximum nanoparticle mass yield of ~39%. Finally, the particles were characterized in terms of crosslink density, showing an efficient encapsulation of the studied salt and a promising path for in-vivo testing. This study helped us develop a reproduceable formulation of an IPMP process that yields stable nanoparticles with suitable therapeutic levels of phosphates. [1] Hyoju, S.K. et al, “Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa”, Annals of Surgery, Feb, 2017. [2]Vadlamudi, S. et al., “Inverse miniemulsion polymerization of phosphate-loaded hydrogel nanoparticles for sepsis prevention”, Unpublished master dissertation, Illinois Institute of Technology, Chicago, Illinois (2014) [3] Yin Y et al, “De Novo Synthesis and Functional Analysis of Polyphosphate-Loaded Poly(Ethylene) Glycol Hydrogel Nanoparticles Targeting Pyocyanin and Pyoverdin Production in Pseudomonas aeruginosa as a Model Intestinal Pathogen”. Annals of Biomedical Engineering. 45(4):1058-1068, 2017. [4] Shinoda, K., & Takeda, H. “The effect of added salts in water on the hydrophile-lipophile balance of nonionic surfactants: The effect of added salts on the phase inversion temperature of emulsions”. Journal of Colloid And Interface Science, 32(4), 642–646, 1970

Impact of preoperative therapy on patterns of recurrence in pancreatic cancer

AbstractBackgroundA theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence.MethodsMedical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan–Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis.ResultsPreoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis.ConclusionsPreoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection

Patients with early rheumatoid arthritis exhibit elevated autoantibody titers against mildly oxidized low-density lipoprotein and exhibit decreased activity of the lipoprotein-associated phospholipase A(2)

Rheumatoid arthritis is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. Oxidized low-density lipoprotein (oxLDL), the antibodies against oxLDL and the lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)) may play important roles in inflammation and atherosclerosis. We investigated the plasma levels of oxLDL and Lp-PLA(2 )activity as well as the autoantibody titers against mildly oxLDL in patients with early rheumatoid arthritis (ERA). The long-term effects of immunointervention on these parameters in patients with active disease were also determined. Fifty-eight ERA patients who met the American College of Rheumatology criteria were included in the study. Patients were treated with methotrexate and prednisone. Sixty-three apparently healthy volunteers also participated in the study and served as controls. Three different types of mildly oxLDL were prepared at the end of the lag, propagation and decomposition phases of oxidation. The serum autoantibody titers of the IgG type against all types of oxLDL were determined by an ELISA method. The plasma levels of oxLDL and the Lp-PLA(2 )activity were determined by an ELISA method and by the trichloroacetic acid precipitation procedure, respectively. At baseline, ERA patients exhibited elevated autoantibody titers against all types of mildly oxLDL as well as low activity of the total plasma Lp-PLA(2 )and the Lp-PLA(2 )associated with the high-density lipoprotein, compared with controls. Multivariate regression analysis showed that the elevated autoantibody titers towards oxLDL at the end of the decomposition phase of oxidation and the low plasma Lp-PLA(2 )activity are independently associated with ERA. After immunointervention autoantibody titers against all types of oxLDL were decreased in parallel to the increase in high-density lipoprotein-cholesterol and high-density lipoprotein-Lp-PLA(2 )activity. We conclude that elevated autoantibody titers against oxLDL at the end of the decomposition phase of oxidation and low plasma Lp-PLA(2 )activity are feature characteristics of patients with ERA, suggesting an important role of these parameters in the pathophysiology of ERA as well as in the accelerated atherosclerosis observed in these patients

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 ± 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients

MINERALOGY AND GEOCHEMISTRY OF THE TRIADESGALANA PB-ZN-AG-AU INTERMEDIATE-HIGH SULFIDATION EPITHERMAL MINERALIZATION, MILOS ISLAND, GREECE

Η μεταλλοφορία Pb-Zn-Ag-Au Τριάδων-Γαλανών στη ΒΔ Μήλο, αποτελεί μία επιθερμική μεταλλοφορία ρηχού θαλάσσιου περιβάλλοντος που αποτέθηκε κατά μήκος ρηγμάτων ΒΑ διεύθυνσης. Πετρώματα ξενιστές είναι πυροκλαστικά ηλικίας 2.5-1.4 εκ. χρόνων και ανδεσιτικοί/δακιτικοί δόμοι λάβας, με τους οποίους και συνδέεται γενετικά. Η μεταλλοφορία απαντά υπό μορφή λατυποπαγών, φλεβών και πλέγματος φλεβιδίων χαλαζία-βαρίτη-γαληνίτη εντός πετρωμάτων εξαλλοιωμένων σε σερικίτη-αδουλάριου και καολινίτη. Η μεταλλοφορία είναι εμπλουτισμένο σε Mo, W, καθώς και σε βασικά 1970 και πολύτιμα μέταλλα (e.g. Pb, Zn, Ag), όπως και οι γειτονικές μεταλλοφορίες του Κοντάρου-Κατσιμουτίου και Βανίου, υποδεικνύοντας μία κοινή μαγματική πηγή στο βάθος που τροφοδότησε τις μεταλλοφορίες αυτές σε μέταλλα και πτητικά συστατικά. Παραγενετικά δεδομένα υποδεικνύουν αρχική απόθεση σιδηροπυρίτη, και στη συνέχεια φαματινίτη, πολυβασίτη, πυραργυρίτη και Ag-ούχου τετραεδρίτη, και τέλος εναργίτη, παρέχοντας ενδείξεις μεταβαλλόμενων συνθηκών θείωσης κατά τη διάρκειας της μεταλλοφορίας. Η εξέλιξη των ρευστών πλούσιων σε Sb στα αρχικά στάδια πρός As- ούχα ρευστά στα τελευταία στάδια, αποτελεί ένδειξη μιάς νέας μαγματικής συνεισφοράς (πιθανόν υπό μορφή μαγματικών αερίων) στο υδροθερμικό σύστημα. Ο άργυρος απαντά στη δομή των θειοαλάτων (έως 66.2 % κ.β. στον πολυβασίτη, 15.1 % κ.β. στον τετραεδρίτη και 60 % κ.β. στον πυραργυρίτη). Διαδικασίες βρασμού (όπως υποδεικνύει η παρουσία αδουλάριου στη παραγένεση ενδιάμεσης θείωσης), και ανάμειξης με θαλασσινό νερό (παρουσία υπογενετικού χλωριδίου του μολύβδου), σύγχρονες με ανάδυση της περιοχής, έχουν συνεισφέρει στην απόθεση του μεταλλεύματοςThe Triades-Galana Pb-Zn-Ag-Au mineralization is a shallow-submarine epithermal mineralization located along NE-trending faults, NW Milos Island, Greece. It is hosted in 2.5–1.4 Ma pyroclastic rocks and is genetically related to andesitic/dacitic lava domes. Mineralization occurs as breccias, quartz-barite galena veins and stockworks within sericite-adularia or kaolinitic altered rocks. The mineralization is enriched in Mo, W and base- and precious metals (e.g. Pb, Zn, Ag) similarly to the neighbouring mineralization at Kondaros-Katsimouti and Vani, indicating common source of metals from a deep buried granitoid feeding western Milos with metals and volatiles. Paragenetic relations suggest early deposition of pyrite, followed by famatinite, polybasite and Ag-rich tetrahedrite, and then by enargite, suggesting fluctuating sulfidation states during ore formation. The evolution from Sb- towards As-rich enrichment indicate a renewed magmatic pulse (probably in the form of magmatic gases) in the hydrothermal system. Silver is present in the structure of sulfosalts (up to 66.2 wt.% in polybasite-pearceite, 15.1 wt.% in tetrahedrite and 60 wt. % in pyrargyrite). Boiling processes (as evidenced by the presence of adularia accompanying intermediate-sulfidation ore) and mixing with seawater (presence of hypogene lead chlorides) and contemporaneous uplift, contributed to ore formation

Preoperative FDG-PET/CT Is an Important Tool in the Management of Patients with Thick (T4) Melanoma

The yield of preoperative PET/CT (PET/CT) for regional and distant metastases for thin/intermediate thickness melanoma is low. Objective of this study is to determine if PET/CT performed for T4 melanomas helps guide management and alter treatment plans. Methods. Retrospective cohort of 216 patients with T4 melanomas treated at two tertiary institutions. Fifty-six patients met our inclusion criteria (T4 lesion, PET/CT and no clinical evidence of metastatic disease). Results. Fifty-six patients (M: 32, F: 24) with median tumor thickness of 6 mm were identified. PET/CT recognized twelve with regional and four patients with metastatic disease. Melanoma-related treatment plan was altered in 11% of the cases based on PET/CT findings. PET/CT was negative 60% of the time, in 35% of the cases; it identified incidental findings that required further evaluation. Conclusion. Patients with T4 lesions, PET/CT changed the treatment plan 18% of the time. Regional findings changed the surgical treatment plan in 11% and the adjuvant plan in 7% of our cases due to the finding of metastatic disease. Additionally 20 patients had incidental findings that required further workup. In this subset of patients, we feel there is a benefit to PET/CT, and further studies should be performed to validate our findings

Control and ultrasonic actuation of a gas-liquid interface in a microfluidic chip

This article describes the design and manufacturing of a microfluidic chip, allowing for the actuation of a gas-liquid interface and of the neighboring fluid. A first way to control the interface motion is to apply a pressure difference across it. In this case, the efficiency of three different micro-geometries at anchoring the interface is compared. Also, the critical pressures needed to move the interface are measured and compared to theoretical result. A second way to control the interface motion is by ultrasonic excitation. When the excitation is weak, the interface exhibits traveling waves, which follow a dispersion equation. At stronger ultrasonic levels, standing waves appear on the interface, with frequencies that are half integer multiple of the excitation frequency. An associated microstreaming flow field observed in the vicinity of the interface is characterized. The meniscus and associated streaming flow have the potential to transport particles and mix reagents