Determination and investigation of defect domains in multi-shape monolayer tungsten disulfide.

Single-layer tungsten disulfide (WS2) is among the most widely investigated two-dimensional materials. Synthesizing it over large areas would enable the exploitation of its appealing optical and electronic properties in industrial applications. However, defects of different nature, concentration and distribution profoundly affect the optical as well as the electronic properties of this crystal. Controlling the defect density distribution can be an effective way to tailor the local dielectric environment and therefore the electronic properties of the system. In this work we investigate the defects in single-layer WS2, grown in different shapes by liquid phase chemical vapor deposition, where the concentration of certain defect species can be controlled by the growth conditions. The properties of the material are surveyed by means of optical spectroscopy, photoelectron spectroscopy and Kelvin probe force microscopy. We determine the chemical nature of the defects and study their influence on the optical and electronic properties of WS2. This work contributes to the understanding of the microscopic nature of the intrinsic defects in WS2, helping the development of defect-based technologies which rely on the control and engineering of defects in dielectric 2D crystals.

Cause or effect? Undetectable vitamin D in a patient with Crohn's disease.

Crohn's disease has been described as the "great mimicker" with a wide array of presentations. We describe a case of a teenager who presented with tetany and undetectable vitamin D as initial presentation of Crohn's disease. There are reports of adults in tetany due to electrolyte derangements in chronic gastrointestinal diseases secondary to malabsorption. However, the role of deficient vitamin D as it contributes to immune system dysfunction has only begun to be explored. Vitamin D is essential for calcium absorption, immune regulation, and gut epithelial barrier. This case report discusses vitamin D physiology and its potential mediation in the pathogenesis of inflammatory bowel disease.

Automated source of squeezed vacuum states driven by finite state machine based software.

In the last few decades, much effort has been made for the production of squeezed vacuum states in order to reduce quantum noise in the audio-frequency band. This technique has been implemented in all running gravitational-wave interferometric detectors and helped to improve their sensitivity. While the detectors are acquiring data for astrophysical observations, they must be kept in the operating condition, also called "science mode," that is, a state that requires the highest possible duty-cycle for all the instrumental parts and controls. We report the development of a highly automated setup for the generation of optical squeezed states, where all the required control loops are supervised by a software based on finite state machines; we took special care to grant ease of use, stability of operation, and possibility of auto-recovery. Moreover, the setup has been designed to be compatible with the existing software and hardware infrastructure of the Virgo detector. In this paper, we discuss the optical properties of this squeezing setup, the locking techniques, and the automation algorithms.

Pulseless Electrical Activity as the Initial Cardiac Arrest Rhythm: Importance of Preexisting Left Ventricular Function.

Background Pulseless electrical activity (PEA) is a common initial rhythm in cardiac arrest. A substantial number of PEA arrests are caused by coronary ischemia in the setting of acute coronary occlusion, but the underlying mechanism is not well understood. We hypothesized that the initial rhythm in patients with acute coronary occlusion is more likely to be PEA than ventricular fibrillation in those with prearrest severe left ventricular dysfunction. Methods and Results We studied the initial cardiac arrest rhythm induced by acute left anterior descending coronary occlusion in swine without and with preexisting severe left ventricular dysfunction induced by prior infarcts in non-left anterior descending coronary territories. Balloon occlusion resulted in ventricular fibrillation in 18 of 34 naïve animals, occurring 23.5±9.0 minutes following occlusion, and PEA in 1 animal. However, all 18 animals with severe prearrest left ventricular dysfunction (ejection fraction 15±5%) developed PEA 1.7±1.1 minutes after occlusion. Conclusions Acute coronary ischemia in the setting of severe left ventricular dysfunction produces PEA because of acute pump failure, which occurs almost immediately after coronary occlusion. After the onset of coronary ischemia, PEA occurred significantly earlier than ventricular fibrillation (<2 minutes versus 20 minutes). These findings support the notion that patients with baseline left ventricular dysfunction and suspected coronary disease who develop PEA should be evaluated for acute coronary occlusion.

A precursor mechanism triggering the second magnetization peak phenomenon in superconducting materials.

The correlation in type-II superconductors between the creep rate S and the Second Magnetization Peak (SMP) phenomenon which produces an increase in Jc, as a function of the field (H), has been investigated at different temperatures by starting from the minimum in S(H) and the onset of the SMP phenomenon detected on a FeSe0.5Te0.5 sample. Then the analysis has been extended by considering the entire S(H) curves and comparing our results with those of many other superconducting materials reported in literature. In this way, we find evidence that the flux dynamic mechanisms behind the appearance of the SMP phenomenon in Jc(H) are activated at fields well below those where the critical current starts effectively to increase. Moreover, the found universal relation between the minimum in the S(H) and the SMP phenomenon in Jc(H) shows that both can be attributed to a sequential crossover between a less effective pinning (losing its effectiveness at low fields) to a more effective pinning (still acting at high fields), regardless of the type-II superconductor taken into consideration.

Orbital Reconstruction via Deformable Titanium Mesh Following Spheno-Orbital Meningioma Resection: Ophthalmic Presentation and Outcomes.

PURPOSE: To present a surgical approach to reconstruction of the bony orbit following resection of spheno-orbital meningioma utilizing deformable titanium mesh while emphasizing the ophthalmic presentation and outcomes of the repair. METHODS: A retrospective chart review received International Review Board approval, and 20 patients met the inclusion criteria. All patients underwent resection of spheno-orbital meningioma followed by orbital reconstruction with deformable titanium mesh. Pre- and postoperative ophthalmic exam findings were recorded. Outcome measures include Snellen visual acuity, performance on automated Humphry 30-2 perimetry, extraocular motility, Hertel exophthalmometry, associated complications, and recurrence. A literature review of the use of titanium to reconstruct the orbit following resection of spheno-orbital meningioma was performed. RESULTS: Visual acuity improved (9/20) or remained the same (8/20) in 85% of patients. Fifteen of the 20 patients had pre- and postoperative visual fields performed, and 93% (14/15) experienced substantial improvement or no change with full fields. Of the 12 patients who had extraocular motility disturbance following surgery, 25% (3/12) had preexisting defects that did not change, 58% (7/12) returned to normal, and 17% (2/12) had new onset dysfunction that did not improve. Proptosis was reduced by a mean of 4.4 mm. Complications were rare and inconsequential, and recurrence was observed in 20% (4/20) at an average of 43 months following surgery. CONCLUSIONS: Orbital reconstruction using deformable titanium mesh is both safe and effective in the setting of resection of spheno-orbital meningioma. This study is the largest known report of orbits reconstructed with deformable titanium mesh in the available literature.The ophthalmic presentation of spheno-orbital meningioma and postoperative results are presented following description of orbital reconstruction utilizing deformable titanium mesh.

Pinning energy and anisotropy properties of a Fe(Se, Te) iron based superconductor.

The measurements of DC magnetization M as a function of magnetic field (H) and time (t) have been performed in order to study the superconducting and pinning properties of a Fe(Se, Te) iron based superconductor fabricated by means of the Bridgman technique. By performing the superconducting hysteresis loops M(H) at different temperatures in the case of perpendicular and parallel field, the critical current density Jc (H) has been extracted in the framework of the Bean critical state model for both configurations. The Jc (H) curves have shown the presence of the second magnetization peak effect that causes an anomalous increase in the field dependence of the critical current density. In order to obtain the Jc anisotropy of the sample, we have performed the ratio between perpendicular and parallel critical current density values [Formula: see text] and compared its values with the literature ones. The information regarding the pinning energy U have been extracted by means of the relaxation of the irreversible magnetization M(t) in the case H∣∣c. In particular, performing relaxation measurements at different temperatures and magnetic fields, the temperature dependence of the pinning energy U(T) at different magnetic fields has been obtained showing an anomalous temperature scaling of the curves. The presence of a maximum in the U(T) curves suggests a pinning crossover at a given field and temperature H cr(T). The H cr(T) values have been fitted with the equation H cr(T) = H cr(0) (1 - T/T*) n whose results confirm the correlation between the elastic/plastic crossover and the end of the peak effect phenomenon.

Soft Tissue Chondroma of the Eyelid.

A 54-year-old woman presented with a 2-year history of a slow-growing subcutaneous nodule of the medial right lower eyelid adjacent to the inferior canaliculus. The patient reported right-sided epiphora suggesting lacrimal outflow obstruction. The surgically excised nodule was consistent with a chondroma. A rare tumor, soft tissue chondroma, is most often seen in the extremities, but has also been observed in the head and neck region. To their knowledge, this is the first reported case of a soft tissue chondroma of the eyelid.

The effects of phytase and xylanase supplementation on performance and egg quality in laying hens.

1. The aim of this study was to evaluate the effects of phytase and xylanase and their interaction on laying hen performance, egg quality, phosphorus (P) digestibility, phytate breakdown, volatile fatty acid (VFA) production and peptide YY concentration. 2. Two hundred and forty hens were allocated to cages at 22 weeks of age based on a 3 × 2 arrangement with phytase (0, 300 or 1500 FTU/kg) and xylanase (0 or 12 000 BXU/kg) as factors. 3. Phytase increased hen-day production (P < 0.05), daily egg mass (P < 0.05) and P digestibility with increasing levels of phytase (P < 0.001). Phytase fed at 1500 FTU/kg reduced IP6 and IP5 and increased myo-inositol concentration in gizzard digesta (P < 0.05). Phytase fed at 300 FTU/kg reduced IP6 in ileal digesta (P < 0.05); however, IP6 and IP5 were further reduced and myo-inositol increased when phytase was added at 1500 FTU/kg (P < 0.05). 4. Xylanase improved feed efficiency when phytase was fed at 300 FTU/kg (P < 0.05). In the absence of phytase, xylanase reduced dry matter and Ca digestibilities (P < 0.05). 5. Neither phytase nor xylanase had an effect on peptide YY or caecal VFA concentrations.

Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil.

The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited. STUDY DESIGN: In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. RESULTS: In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B2 and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. CONCLUSION: The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.

Demagnetization harmonic effects on the magnetization of granular systems on a macroscopic scale: the superconducting case.

A model has been developed to determine the effective ac magnetic response of magnetic systems, taking into account the demagnetization effects arising from the sample geometry which determine the out-of-phase components of the applied fundamental frequency and higher harmonic components. Indeed, demagnetization fields and their intermodulation can significantly affect the ac magnetic response. This approach provides a system of self-consistent linear equations relating the magnetic response to the external magnetic field by means of nonlinear magnetic susceptibility. The model is extended to the magnetic response of granular systems in terms of the contributions of the individual grains and of the whole sample in the presence of demagnetization effects of the whole sample and of the grains on a macroscopic scale. In particular, our model is applied to a granular superconducting system. The comparison between the performed numerical simulations and the experimental data shows that the demagnetization fields of the single grains and of the whole sample, and their intermodulation, are relevant if magnetic measurements are used to extract detailed information about the analyzed material.

Innovative technology for colostomy irrigation: assessing the impact on patients.

AIM: The main purpose of the trial was to evaluate the opinions expressed by a sample of subjects with permanent colostomy, as a result of the use of a new device designed for the execution of transtomal intestinal irrigation; their feedback was analyzed in relation to the concept of Quality of Life. METHODS: The device was tested on a sample of 14 colostomized patients (10 men and 4 women, aged between 42 and 77 years) who were used to perform intestinal irrigation procedures independently and routinely, with standard technique. After testing the new device, the patients included in the study were asked to fill out a questionnaire built ad hoc for their situation. RESULTS: The analysis of the data collected led to the following conclusions: 93% of the patients described the new irrigation method as simpler than the standard procedure; the majority of the patients assessed bowel emptying as good; 64% of patients reported excellent comfort experienced during the procedure; the presence of a regulator to adjust the instillation speed of water into the intestinal lumen was considered useful to control the flow of the incoming fluid CONCLUSION: The use of the device guaranteed: psychological tranquility, minimum manual intervention, full achievement of the expected results and decrease in the issues normally encountered with the standard irrigation method. The practical features of the new device ensure easy and straightforward carrying out of the procedure; this ease of use affects the stomized patient's everyday life by reducing the time of procedure completion, thus positively influencing the perception of the patients' Quality of Life.

Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors.

PURPOSE: This is a first-in-human, phase I, dose-escalation study to determine the maximum tolerated dose (MTD) of intravenous, flat-dosed ST-1968 (namitecan), a new hydrophilic camptothecan derivative. METHODS: Namitecan was administered intravenously over 2 h on day 1 and day 8 every 21 days (D1-D8-Q21D), starting at a flat dose of 2.5 mg, and increased according to a 3 + 3 cohort design. Due to frequent skipping of day 8 dosing for cytopenias, the study was expanded to test namitecan dosing on day 1 every 21 days (D1-Q21) at a starting dose of 17.5 mg. Major dose-limiting toxicity (DLT) was defined as grade (G) 4 neutropenia persisting >5 days, febrile neutropenia, G3 thrombocytopenia or G2 non-hematological toxicity. RESULTS: Thirty-four patients were included into the D1-D8-Q21D group (2.5, 5, 10, 15, 17.5, 20 mg dosing cohorts), 29 patients into the D1-21D group (17.5, 20, 23, 27, 30 mg dosing cohorts). Neutropenia was the DLT in both groups, with 15 mg being defined as the recommended dose (RD) for the D1-D8-Q21D group, and 23 mg for the D1-Q21D group. Non-hematological toxicity was negligible. One patient with endometrial cancer in the D1-D8-Q21D group and one patient with cholangiocellular carcinoma in the D1-Q21D group experienced a partial remission. Namitecan exhibited fully dose-proportional pharmacokinetics. CONCLUSIONS: This study demonstrates clinical safety, favourable pharmacokinetics and preliminary antitumor activity of the novel hydrophilic camptothecin analogue namitecan in patients with heavily pretreated solid malignancies, when given either on a 2 out of 3 weeks or 3-weekly regimen.

Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968).

AIMS: Namitecan is a new camptothecan compound undergoing early clinical development. This study was initiated to build an integrated pharmacokinetic (PK) and pharmacodynamic (PD) population model of namitecan to guide future clinical development. METHODS: Plasma concentration-time data, neutrophils and thrombocytes were pooled from two phase 1 studies in 90 patients with advanced solid tumours, receiving namitecan as a 2 h infusion on days 1 and 8 every 3 weeks (D1,8) (n = 34), once every 3 weeks (D1) (n = 29) and on 3 consecutive days (D1-3) (n = 27). A linear three compartment PK model was coupled to a semiphysiological PD-model for neutrophils and thrombocytes. Data simulations were used to interrogate various dosing regimens and give dosing recommendations. RESULTS: Clearance was estimated to be 0.15 l h(-1), with a long terminal half-life of 48 h. Body surface area was not associated with clearance, supporting flat-dosing of namitecan. A significant and clinically relevant association was found between namitecan area under the concentration-time curve (AUC) and the percentage drop of neutrophils (r(2) = 0.51, P < 10(-4)) or thrombocytes (r(2) = 0.49, P < 10(-4)). With a target for haematological dose-limiting toxicity of <20%, the recommended dose was defined as 12.5 mg for the D1,8 regimen, 23 mg for the once every 3 week regimen and 7 mg for the D1-3 regimen. CONCLUSION: This is the first integrated population PK-PD analysis of the new hydrophilic topoisomerase I inhibitor namitecan, that is currently undergoing early clinical development. A distinct relationship was found between drug exposure and haematological toxicity, supporting flat-dosing once every 3 weeks as the most adequate dosing regimen.

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development.

Should atypia of undetermined significance be subclassified to better estimate risk of thyroid cancer?

BACKGROUND: Atypia or follicular lesion of undetermined significance (AUS) is a cytologic category of thyroid aspirates with a wide range of reported malignancy. We aimed to determine whether specific cytologic features are associated with different rates of thyroid malignancy. METHODS: All thyroid fine needle aspiration biopsies with AUS from 2010 to 2012 were reanalyzed. Cytologic features were correlated with final pathology. Cytopathologists were blinded to the original cytologic interpretation and final diagnosis. RESULTS: Seventy-six patients had AUS; 39 (54%) underwent surgery with a malignancy rate of 18%. Specimens with moderate or large amount of thin colloid and absent or few nuclear inclusions had a >88% rate of benign disease. More than rare nuclear inclusions or grooves were associated with a higher rate of cancer (75% vs 9%, P = .005; 45% vs 7%, P = .003). CONCLUSIONS: Patients with AUS and more than rare nuclear inclusions or grooves are at higher risk for cancer and should forego repeat fine needle aspiration biopsy and undergo thyroidectomy.

Assessment of coagulation and potential biochemical markers for hypercoagulability in canine hyperadrenocorticism.

BACKGROUND: Anecdotal accounts and limited research suggest that dogs with spontaneous hyperadrenocorticism (HAC) are at risk of developing thromboembolic complications. Detailed description of coagulation status and identification of subsets of dogs at greatest risk would impact therapeutic recommendations for these patients. HYPOTHESIS: A subset of dogs with HAC will have a hypercoagulable tendency as identified by increased procoagulant activity, decreased fibrinolysis, or both. Objective 1: To document the existence of this hypercoagulable tendency in HAC dogs using assays of individual coagulation factors, fibrinolytic activity, and systemic coagulation. Objective 2: To evaluate clinical and biochemical markers in HAC dogs to identify a subset of HAC patients at increased risk of this hypercoagulable tendency. ANIMALS: Seventeen dogs newly diagnosed with HAC. METHODS: Prospective study. Medical history, physical examination findings, routine diagnostic tests, and comprehensive coagulation testing were performed at the time of HAC diagnosis. Coagulation parameters were assessed individually and as panels for each dog. Historical and clinical variables were correlated with coagulation parameters to identify risk factors. RESULTS: The majority (88.2%) of HAC dogs exhibited a hypercoagulable tendency. Abnormalities in 1 coagulation assay did not predict abnormalities in others. Duration of clinical signs of HAC did not predict hypercoagulability. Comorbid conditions or abnormal clinicopathologic parameters that predicted hypercoagulability were not identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Although HAC dogs may demonstrate a hypercoagulable tendency individually and as a group, comorbid conditions or biochemical variables that would predict more severe coagulation abnormalities were not identified.

Yield of repeat fine-needle aspiration biopsy and rate of malignancy in patients with atypia or follicular lesion of undetermined significance: the impact of the Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND: Atypia/follicular lesion of undetermined significance (A/FLUS) is a new category in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) for which repeat fine-needle aspiration biopsy (FNAB) is recommended. METHODS: A retrospective review was completed to evaluate the impact of the BSRTC on management of nodular thyroid disease. Patients were divided into pre-BSRTC and BSRTC groups. A comparative analysis of cytopathologic diagnoses and rates of repeat FNAB and malignancy was completed. RESULTS: FNAB was performed in 730 patients: 337 pre-BSRTC and 393 BSRTC. There was a decrease in follicular/Hürthle cell neoplasm (FN/HCN; 9.5% vs 3.6%, P = .001) but no difference in the rate of malignancy (6.5% vs 6.4%, P = 1.0). Fewer operations (29% vs 21%, P = .02) and more repeat FNABs (3.9% vs 11%, P < .001) were performed in the BSRTC group. Sixty-one (16%) patients had A/FLUS, 56 with complete follow-up. Repeat FNAB in 26 patients was benign (11), A/FLUS (6), suspicious for malignancy (4), FN/HCN (2), and nondiagnostic (3). Thirty-two (57%) patients underwent thyroidectomy, and 6 patients (19%) were diagnosed with cancer. CONCLUSION: The BSRTC resulted in more frequent repeat FNAB, fewer thyroidectomies and no change in malignancy rate. In patients with A/FLUS, repeat FNAB was definitive in 65% with a rate of malignancy of 19%.