The interplay between drift and electrical measurement in conduction atomic force microscopy.

In Conduction Atomic Force Microscopy (CAFM), it is sometimes required to monitor electrical data at a single location over an extended period of time. However, thermal drift of the microscope will cause the tip to move with respect to the sample and thus limit the collection of data. We investigate a method to prolong the time a tip dwells at a location by choosing the AFM cantilever to have small spring constants in the lateral directions. The basis of the approach is that the tip can only move (or slip) once the lateral forces caused by drift overcome the friction force pinning the tip to the surface. We demonstrate the effect experimentally using platinum wire tips and diamond coated tips on SiO2 and HfO2 dielectric films. Simultaneous measurement of the current flow and lateral force signals show that the onset of tip slipping correlates with the beginning of a decrease in the measured current flow, and the onset of slip is prolonged for blunt tips or cantilevers having soft lateral spring constants. The approach not only provides a way to improve the CAFM method for time dependent measurements but also assists in interpreting CAFM data in the presence of drift.

Conductive Atomic Force Microscope Study of Bipolar and Threshold Resistive Switching in 2D Hexagonal Boron Nitride Films.

This study investigates the resistive switching characteristics and underlying mechanism in 2D layered hexagonal boron nitride (h-BN) dielectric films using conductive atomic force microscopy. A combination of bipolar and threshold resistive switching is observed consistently on multi-layer h-BN/Cu stacks in the low power regime with current compliance (I comp ) of less than 100 nA. Standard random telegraph noise signatures were observed in the low resistance state (LRS), similar to the trends in oxygen vacancy-based RRAM devices. While h-BN appears to be a good candidate in terms of switching performance and endurance, it performs poorly in terms of retention lifetime due to the self-recovery of LRS state (similar to recovery of soft breakdown in oxide-based dielectrics) that is consistently observed at all locations without requiring any change in the voltage polarity for I comp ~1-100 nA.

Vitamin D, vitamin A, the primary melanoma transcriptome and survival.

Survival from melanoma is influenced by several, well-established clinical and histopathological factors, e.g. age, Breslow thickness and microscopic ulceration. We (the Section of Epidemiology and Biostatistics, University of Leeds) have carried out research to better understand the biological basis for these observations. Preliminary results indicated a protective role for vitamin D in melanoma relapse and that higher vitamin D was associated with thinner primary melanomas. Funding from the British Skin Foundation enabled JNB to establish a study of the effects of vitamin A in melanoma. The results suggested that vitamin A could reduce the protective effect of vitamin D in terms of overall survival. Therefore, we propose that vitamin D3 supplementation alone might be preferable to combined multivitamin preparations, where vitamin D supplementation is deemed to be appropriate. Proving a causal link between vitamin D and melanoma-specific survival is challenging. We have shown limited evidence of causation in a Mendelian randomization experiment (described in more detail later). Recent work in Leeds has also shown that higher vitamin D may be protective for microscopic ulceration. Taken together, vitamin D appears to be associated with less aggressive primary melanomas and may itself influence outcome. We continue to explore the role of vitamin D in melanoma survival and the optimum levels that might be crucial.

Measurements of δ13C in CH4 and using particle dispersion modeling to characterize sources of Arctic methane within an air mass.

A stratified air mass enriched in methane (CH4) was sampled at ~600 m to ~2000 m altitude, between the north coast of Norway and Svalbard as part of the Methane in the Arctic: Measurements and Modelling campaign on board the UK's BAe-146-301 Atmospheric Research Aircraft. The approach used here, which combines interpretation of multiple tracers with transport modeling, enables better understanding of the emission sources that contribute to the background mixing ratios of CH4 in the Arctic. Importantly, it allows constraints to be placed on the location and isotopic bulk signature of the emission source(s). Measurements of δ13C in CH4 in whole air samples taken while traversing the air mass identified that the source(s) had a strongly depleted bulk δ13C CH4 isotopic signature of -70 (±2.1)‰. Combined Numerical Atmospheric-dispersion Modeling Environment and inventory analysis indicates that the air mass was recently in the planetary boundary layer over northwest Russia and the Barents Sea, with the likely dominant source of methane being from wetlands in that region.

Nanoscale Trapping and Squeeze-Out of Confined Alkane Monolayers.

We present combined force curve and conduction atomic force microscopy (AFM) data for the linear alkanes CnH2n+2 (n = 10, 12, 14, 16) confined between a gold-coated AFM tip and a graphite surface. Solvation layering is observed in the force curves for all liquids, and conduction AFM is used to study in detail the removal of the confined (mono)layer closest to the graphite surface. The squeeze-out behavior of the monolayer can be very different depending upon the temperature. Below the monolayer melting transition temperatures the molecules are in an ordered state on the graphite surface, and fast and complete removal of the confined molecules is observed. However, above the melting transition temperature the molecules are in a disordered state, and even at large applied pressure a few liquid molecules are trapped within the tip-sample contact zone. These findings are similar to a previous study for branched alkanes [ Gosvami Phys. Rev. Lett. 2008, 100, 076101 ], but the observation for the linear alkane homologue series demonstrates clearly the dependence of the squeeze-out and trapping on the state of the confined material.

Friction measurement on free standing plates using atomic force microscopy.

A method is introduced to measure friction on small, free standing objects, specifically microfabricated silicon plates, based on atomic force microscopy (AFM). An AFM tip is brought into contact with the plate resting on a substrate. The substrate is displaced laterally and, provided the AFM tip does not slide over the plate, the twisting of the AFM cantilever is used to measure the friction of the underlying plate-substrate interface. The method can measure nano-Newton to micro-Newton forces (both friction and applied load) and provides a means to measure friction of macroscopic structures at low load.

Electroplated CoPt magnets for actuation of stiff cantilevers.

A cantilever has been microfabricated for use in non-contact Atomic Force Microscopy (AFM) using a very thick magnetic film to actuate the cantilever motion. The thick magnetic block is deposited electrochemically over a defined area of the cantilever. This cantilever is particularly suitable for driving stiff AFM cantilevers in a liquid environment. Clean mechanical resonances are easily observed. Examples are given of a hard (CoPt) magnet of dimension 29 × 21 × 6 µm(3) electroplated on Silicon cantilevers of stiffness ~22 N/m, giving a static displacement of ~0.2 nm in an applied field of 10(-3) T.

Complete skin examination is essential in the assessment of dermatology patients: findings from 483 patients.

BACKGROUND: Dermatological teaching has traditionally stressed that complete skin examination is essential in the assessment of patients with potential skin disease. OBJECTIVES: To determine whether complete skin examination results in increased diagnoses of skin malignancies that would not have been discovered otherwise. METHODS: New patients (n = 483) attending a dermatology clinic in a university teaching hospital and private dermatology practice had a complete skin examination, as is our normal practice. These patients were seen over a 9-month period (January-September 2009). All patients were examined by the same consultant dermatologist. Data were collected on patients' sex, age, presenting complaint and findings on complete skin examination. RESULTS: Two nodular malignant melanomas with mean Breslow thickness of 0·6 mm (0·4%) and one melanoma in situ were identified at sites distant from the patient's presenting complaint. Sixteen patients (3·3%) had a basal cell carcinoma that would not have been discovered if the presenting lesion alone had been examined. Thirty-three patients (6·8%) had actinic keratoses or squamous cell carcinoma in situ and nine (1·9%) had dysplastic naevi. A further 21 patients (4·3%) had a suspicious lesion biopsied or excised with subsequent benign histology. Seventy-three patients (15·1%) had other benign dermatological diagnoses requiring treatment or investigation. CONCLUSIONS: In a 9-month period, in a sample of 483 new patients, three patients (0·6%) had potentially lethal skin malignancies identified that would not have been diagnosed without a complete skin examination. Sixteen (3·3%) patients had basal cell carcinomas that would have been missed without complete skin examination. This study confirms the traditional teaching that complete skin examination has the potential to reduce morbidity and mortality from cutaneous malignancy.

Alcohol misuse in patients with psoriasis: identification and relationship to disease severity and psychological distress.

BACKGROUND: Moderate to severe psoriasis is associated with increased alcohol intake and excessive mortality from alcohol-related causes. Alcohol biomarkers provide an objective measure of alcohol consumption. Carbohydrate-deficient transferrin (CDT) is the single most sensitive and specific alcohol biomarker. OBJECTIVES: To assess alcohol consumption in a cohort of patients with moderate to severe psoriasis using standard alcohol screening questionnaires and biomarkers. We investigated whether there was an association between alcohol intake, anxiety, depression and disease severity. METHODS: Consecutive patients with chronic plaque psoriasis were recruited and completed a range of anonymized assessments. Psoriasis severity, anxiety and depression, and the impact of psoriasis on quality of life were assessed. Alcohol screening questionnaires were administered. Blood specimens were taken and γ-glutamyltransferase (γGT) and CDT were measured. RESULTS: A total of 135 patients completed the study. Using validated questionnaires, between 22% and 32% had difficulties with alcohol. Seven per cent had CDT > 1·6% indicating a heavy alcohol intake. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire was superior to other validated questionnaires in detecting alcohol misuse. There were no significant associations between measures of excessive alcohol consumption and disease severity. Excessive alcohol intake as measured by the CAGE questionnaire was associated with increased depression (P = 0·001) but other measures of alcohol excess did not correlate with psychological distress. Men had significantly more difficulties with alcohol than women (P < 0·001). CONCLUSION: Alcohol misuse is common in patients with moderate to severe psoriasis. Screening with the AUDIT questionnaire and CDT may allow the identification of patients who are misusing alcohol and allow appropriate intervention.

Temperature dependence of solvation forces as measured in atomic force microscopy.

An atomic force microscope (AFM) has been used to study the effect of temperature on solvation forces in the liquids octamethylcyclotetrasiloxane, n-hexadecane, and n-dodecanol confined between the AFM tip and a graphite surface. Discrete solvation layers can be observed for all three liquids at all the temperatures measured (298-348K). However, with increasing temperature there is a significant decrease in the magnitude of the measured solvation forces and a reduction in the number of solvation oscillations which can be observed. Solvation forces per se are only weakly temperature dependent and the most plausible explanation is that we are measuring how the layers are squeezed from the tip-sample gap. The squeeze out process is a thermally activated phenomenon and gives rise to the large change in the magnitude of the force oscillations with temperature. A simple analysis is provided based on transition rate theory. The large change in solvation force with temperature has implications for the measurement of localized forces using AFM, particularly in interpreting biological interactions and single asperity friction.

Squeeze-out of branched alkanes on graphite.

We study squalane and heptamethylnonane (HMN) confined between a conducting atomic force microscope tip and a graphite surface. Solvation layering occurs for both liquids but marked differences in the squeeze out mechanics are observed for ordered or disordered monolayers. The squalane monolayer at 25 degrees C is an ordered solid, as verified by direct imaging, and the squeeze out can be modeled using elastic continuum mechanics. HMN is in a disordered state at 25 degrees C and cannot be modeled as a single elastic asperity even in solid-solid contact because HMN liquid is trapped in the contact zone.

Solvation and squeeze out of hexadecane on graphite.

We have performed simultaneous force and conductivity measurement of hexadecane liquid confined between a conducting atomic force microscope tip and a graphite surface. Both the current and the force data reveal discrete solvation layering of the hexadecane near the surface. We typically observe that the current does not vary with load in a simple way as the layer closest to the surface is compressed, but increases markedly prior to the expulsion of material from the tip-sample gap. We infer that even for a nanoscale asperity there is conformation change of the confined hexadecane under the tip apex prior to squeeze out of the molecules.

Acute pancreatitis: an under-recognized risk of percutaneous transhepatic distal biliary intervention.

OBJECTIVE: Percutaneous transhepatic biliary intervention (PTBI) plays an important role in the management of biliary obstruction, and this may be complicated by acute pancreatitis. The aim of this study was to assess the incidence of acute pancreatitis following PTBI. PATIENTS AND METHODS: Patients who underwent PTBI between January 1992 and December 2003 in a tertiary referral centre were identified from the hospital database. Patients who did not have their amylase measured post-procedure were excluded, as acute pancreatitis might have been missed. Acute pancreatitis was defined as hyperamylasaemia of three times or more above normal in association with abdominal pain. RESULTS: Over a 12-year period, 331 patients underwent 613 procedures. Serum amylase was measured after 134 procedures (21.9%) and was elevated in 26 of those (19.4%). There was no difference in the frequency of hyperamylasaemia between proximal and distal PTBI (14/73 [19.2%] vs 12/61 [19.7%] procedures, p=NS). However, acute pancreatitis developed after 4 of 61 (6.6%) distal PTBI (stent, n=3; internal-external catheter insertion, n=1) but not after proximal PTBI (cholangiography or external drainage) (p=0.041). The attacks were mild in three of the four patients. No pancreatitis-related deaths occurred. CONCLUSION: The risk of acute pancreatitis after distal PTBI is under-recognized and should be considered as a consent issue in patients scheduled for distal PTBI and when post-procedure abdominal pain ensues.

Discrete solvation layering in confined binary liquids.

The solvation force profiles of squalane/octamethylcyclotetrasiloxane (OMCTS) mixtures confined between Si3N4 tips and highly oriented pyrolytic graphite (HOPG) and hexadecane/OMCTS confined between alkanethiol-functionalized tips and freshly cleaved mica have been measured by atomic force microscopy. Measurements on HOPG reveal oscillatory behavior where discrete solvation layers of both squalane and OMCTS are observed in a single force curve. The large repulsive force of the first solvation layer (squalane) on HOPG indicates that it is strongly bound. Oscillatory behavior is also observed for hexadecane/OMCTS on mica excepting that the oscillations are found in the attractive regime. The OMCTS layers in this case are less ordered with slightly larger (approximately 1 A) periodicities. These results are in agreement with computer simulations for binary liquid mixtures but differ qualitatively from surface force apparatus experiments.

Percutaneous removal of retained calculi from the abdomen.

With rising pressure placed on health service resources minimally invasive techniques requiring only short hospital admissions are increasing in importance. We describe the techniques used to remove calculi from the peritoneal cavity which had been retained after surgery and continued to cause clinical problems. In both cases described the calculi lay within abscess cavities associated with fistulous tracks to the skin. The fistulae were dilated to allow passage of therapeutic radiologic and endoscopic equipment enabling manipulation and subsequent extraction of the stones. In both cases removal of the calculi allowed complete resolution of the fistulae and the patients made a full clinical recovery. Removal of gallstones which have escaped into the peritoneum at laparoscopic cholecystectomy leading to sepsis has been described; we describe the novel management of a patient in whom extraction had already been attempted, at another hospital, without success. Removal of an appendicolith, described here in another patient, does not appear to have been reported previously.

Antibody/antigen affinity behavior in liquid environment with electrical impedance analysis of quartz crystal microbalances.

Electrical impedance analysis has been used to study anti-human immunoglobulin G (anti-h IgG) adsorption and the subsequent human immunoglobulin G (hIgG) or rabbit immunoglobulin G (rIgG) affinity reaction in aqueous liquids on a polystyrene (PS)-modified quartz crystal microbalance (QCM) surface. Time-dependent adsorption data of both the frequency shift and the electrical equivalent parameters (motional resistance, shunt capacitance, quality factor, etc) are monitored. It was found that the motional resistance, R, increases while the resonance frequency, f, decreases during both the anti-h IgG immobilization and the subsequent affinity process. Decreasing f primarily arises from the increased mass loading. Increasing R indicates more power dissipation (increased losses) in the system. The change in motional resistance, delta R, in the affinity reaction is considerably larger than that in anti-h IgG immobilization adsorption process, although the resonant frequency shifts, delta f, are very close in these two processes. Specifically, for a saturated solution, the ratio of delta R/delta f is 9.45 x 10 (-3) Omega/Hz for anti-h IgG adsorption and 28.1 x 10 (-3) omega/Hz for anti-h IgG/hIgG binding respectively, indicating the increased power dissipation with the increasing binding molecules. The shunt capacitance changes little in the hIgG binding process ( approximately 0.01 pF).

Solvation forces in branched molecular liquids.

The solvation force of squalane confined between a silicon tip and a graphite surface has been measured by atomic force microscopy. This highly branched molecule shows oscillatory force profiles similar to those of spherical and linear chain molecules. Squalane molecules closest to the substrate are tightly bound and finer details imply that interdigitation occurs. This agrees with computer simulations for branched molecules but differs qualitatively from force balance experiments. These differences arise from the smaller confinement area and the different chemical nature of the surfaces.