Quantifying SIMS of Organic Mixtures and Depth Profiles-Characterizing Matrix Effects of Fragment Ions.

Sets of matrix factors, Ξ, are reported for the first time for secondary ions in secondary ion mass spectrometry for several binary organic systems. These show the interplay of the effects of ion velocity, fragment chemistry, and the secondary ion point of origin. Matrix factors are reported for negative ions for Irganox 1010 with FMOC or Irganox 1098 and, for both positive and negative ions, with Ir(ppy)2(acac). For Irganox 1010/FMOC, the Ξ values for Irganox 1010 fall with m/z, whereas those for FMOC rise. For m/z < 250, Ξ scales very approximately with (m/z)0.5, supporting a dependence on the ion velocity at low mass. Low-mass ions generally have low matrix factors but |Ξ| may still exceed 0.5 for m/z < 50. Analysis of ion sequences with addition or loss of a hydrogen atom shows that the Ξ values for Irganox 1010 and FMOC ions change by - 0.026 and 0.24 per hydrogen atom, respectively, arising from the changing charge transfer rate constant. This effect adds to that of velocity and may be associated with the nine times more hydrogen atoms in the Irganox 1010 molecule than in FMOC. For Irganox 1098/Irganox 1010, the molecular similarity leads to small |Ξ|, except for the pseudo molecular ions where the behavior follows Irganox 1010/FMOC. For Ir(ppy)2(acac)/Irganox 1010, the positive secondary ions show twice the matrix effects of negative ions. These data provide the first overall assessment of matrix factors in organic mixtures necessary for improved understanding for quantification and the precise localization of species. Graphical Abstract ᅟ.

SIMS of Organic Materials-Interface Location in Argon Gas Cluster Depth Profiles Using Negative Secondary Ions.

A procedure has been established to define the interface position in depth profiles accurately when using secondary ion mass spectrometry and the negative secondary ions. The interface position varies strongly with the extent of the matrix effect and so depends on the secondary ion measured. Intensity profiles have been measured at both fluorenylmethyloxycarbonyl-L-pentafluorophenylalanine (FMOC) to Irganox 1010 and Irganox 1010 to FMOC interfaces for many secondary ions. These profiles show separations of the two interfaces that vary over some 10 nm depending on the secondary ion selected. The shapes of these profiles are strongly governed by matrix effects, slightly weakened by a long wavelength roughening. The matrix effects are separately measured using homogeneous, known mixtures of these two materials. Removal of the matrix and roughening effects give consistent compositional profiles for all ions that are described by an integrated exponentially modified Gaussian (EMG) profile. Use of a simple integrated Gaussian may lead to significant errors. The average interface positions in the compositional profiles are determined to standard uncertainties of 0.19 and 0.14 nm, respectively, using the integrated EMG function. Alternatively, and more simply, it is shown that interface positions and profiles may be deduced from data for several secondary ions with measured matrix factors by simply extrapolating the result to Ξ = 0. Care must be taken in quoting interface resolutions since those measured for predominantly Gaussian interfaces with Ξ above or below zero, without correction, appear significantly better than the true resolution. Graphical Abstract ᅟ.

Swimming-induced pulmonary edema in a tropical climate: a case report.

INTRODUCTION: Swimming-induced pulmonary edema (SIPE) occurs during strenuous physical exertion in cold water and has been reported in scuba divers, free-diving competitors, combat swimmers, and triathletes. We describe a case of SIPE in a combat swimmer in warm tropical waters. CASE REPORT: A 21-year old diver trainee developed dyspnea, chest discomfort and hemoptysis after performing a 2-km sea swim in water temperatures of around 30°C. Over a two-hour period, his oxygen saturations deteriorated. Chest X-ray showed pulmonary edema. He was admitted to the general ward for observation and was given supportive treatment. His symptoms resolved over two days. Repeat CXR was normal. He was reviewed and certified fit to continue with diver training. DISCUSSION: Much of the earlier literature on SIPE describes the development of symptoms after exposure to temperate waters as one main risk factor. This case highlights the risk of development of SIPE in warm tropical waters. With a low reported incidence of SIPE in warm waters, this condition is likely to be underdiagnosed. There is therefore a need to increase local awareness of SIPE in the medical community. A deliberate effort to collate data on SIPE in our local community will help us to better understand the pathophysiology of SIPE in the context of a tropical climate. CONCLUSION: Development of SIPE in tropical waters suggests that other risk factors may be predominant. There should be a high index of suspicion when any strenuous in-water activity is conducted so that timely treatment may be instituted.

Determination of the sputtering yield of cholesterol using Arn(+) and C60(+(+)) cluster ions.

The sputtering yield of cholesterol films on silicon wafers is measured using Arn(+) and C60(+(+)) ions in popular energy (E) and cluster size (n) ranges. It is shown that the C60(+(+)) ions form a surface layer that stabilizes the film so that a well-behaved profile is obtained. On the other hand, the Arn(+) gas clusters leave the material very clean but, at room temperature, the layer readily restructures into molecular bilayers, so that, although a useful measure may be made of the sputtering yield, the profiles become much more complex. This restructuring does not occur at room temperature normally but results from the actions of the beams in the sputtering process for profiling in secondary ion mass spectrometry. Better profiles may be made by reducing the sample temperature to -100 °C. This is likely to be necessary for many lower molecular weight materials (below 1000 Da) to avoid the movement of molecules. Measurements for cholesterol films on 37 nm of amiodarone on silicon are even better behaved and show the same sputtering yields at room temperature as those films directly on silicon at -100 °C. The yields for both C60(+(+)) and Arn(+) fit the Universal Equation to a standard deviation of 11%.

Sampling Depths, Depth Shifts, and Depth Resolutions for Bi(n)(+) Ion Analysis in Argon Gas Cluster Depth Profiles.

Gas cluster sputter depth profiling is increasingly used for the spatially resolved chemical analysis and imaging of organic materials. Here, a study is reported of the sampling depth in secondary ion mass spectrometry depth profiling. It is shown that effects of the sampling depth leads to apparent shifts in depth profiles of Irganox 3114 delta layers in Irganox 1010 sputtered, in the dual beam mode, using 5 keV Ar2000⁺ ions and analyzed with Bi(q+), Bi3(q+) and Bi5(q+) ions (q = 1 or 2) with energies between 13 and 50 keV. The profiles show sharp delta layers, broadened from their intrinsic 1 nm thickness to full widths at half-maxima (fwhm's) of 8-12 nm. For different secondary ions, the centroids of the measured delta layers are shifted deeper or shallower by up to 3 nm from the position measured for the large, 564.36 Da (C33H46N3O5⁻) characteristic ion for Irganox 3114 used to define a reference position. The shifts are linear with the Bi(n)(q+) beam energy and are greatest for Bi3(q+), slightly less for Bi5(q+) with its wider or less deep craters, and significantly less for Bi(q+) where the sputtering yield is very low and the primary ion penetrates more deeply. The shifts increase the fwhm's of the delta layers in a manner consistent with a linearly falling generation and escape depth distribution function (GEDDF) for the emitted secondary ions, relevant for a paraboloid shaped crater. The total depth of this GEDDF is 3.7 times the delta layer shifts. The greatest effect is for the peaks with the greatest shifts, i.e. Bi3(q+) at the highest energy, and for the smaller fragments. It is recommended that low energies be used for the analysis beam and that carefully selected, large, secondary ion fragments are used for measuring depth distributions, or that the analysis be made in the single beam mode using the sputtering Ar cluster ions also for analysis.

Sputtering Yields for Mixtures of Organic Materials Using Argon Gas Cluster Ions.

The sputtering yield volumes of binary mixtures of Irganox 1010 with either Irganox 1098 or Fmoc-pentafluoro-L-phenylalanine (FMOC) have been measured for 5 keV Ar2000(+) ions incident at 45° to the surface normal. The sputtering yields are determined from the doses to sputter through various compositions of 100 nm thick, intimately mixed, layers. Because of matrix effects, the profiles for secondary ions are distorted, and profile shifts in depth of 15 nm are observed leading to errors above 20% in the deduced sputtering yield. Secondary ions are selected to avoid this. The sputtering yield volumes for the mixtures are shown to be lower than those deduced from a linear interpolation from the pure materials. This is shown to be consistent with a simple model involving the changing energy absorbed for the sputtering of intimate mixtures. Evidence to support this comes from the secondary ion data for pairs of the different molecules. Both binary mixtures behave similarly, but matrix effects are stronger for the Irganox 1010/FMOC system.

Depth resolution at organic interfaces sputtered by argon gas cluster ions: the effect of energy, angle and cluster size.

An analysis is presented of the effect of experimental parameters such as energy, angle and cluster size on the depth resolution in depth profiling organic materials using Ar gas cluster ions. The first results are presented of the incident ion angle dependence of the depth resolution, obtained at the Irganox 1010 to silicon interface, from profiles by X-ray photoelectron spectrometry (XPS). By analysis of all relevant published depth profile data, it is shown that such data, from delta layers in secondary ion mass spectrometry (SIMS), correlate with the XPS data from interfaces if it is assumed that the monolayers of the Irganox 1010 adjacent to the wafer substrate surface have an enhanced sputtering rate. SIMS data confirm this enhancement. These results show that the traditional relation for the depth resolution, FWHM = 2.1Y(1/3) or slightly better, FWHM = P(X)Y(1/3)/n(0.2), where n is the argon gas cluster size, and P(X) is a parameter for each material are valid both at the 45° incidence angle of the argon gas cluster sputtering ions used in most studies and at all angles from 0° to 80°. This implies that, for optimal depth profile resolution, 0° or >75° incidence may be significantly better than the 45° traditionally used, especially for the low energy per atom settings required for the best resolved profiles in organic materials. A detailed analysis, however, shows that the FWHM requires a constant contribution added in quadrature to the above such that there are minimal improvements at 0° or greater than 75°. A critical test at 75° confirms the presence of this constant contribution.

Angle dependence of argon gas cluster sputtering yields for organic materials.

The first angle-dependent measurements of the sputtering yield of an organic material using argon gas cluster ions under a wide range of conditions are reported in order to develop an analytical description of the behavior important for the development of the application of secondary ion mass spectrometry to organic and biological systems. Data are presented for Irganox 1010 using argon gas cluster ion beams of 5 and 10 keV energy, E, with cluster sizes, n, from 1000 to 5000. The measurements are conducted in an X-ray photoelectron spectrometer for a range of angles from 0 to 80° from the surface normal. The results support the Universal Equation for argon gas cluster sputtering yields with the angle dependence incorporated into the equation via a simple angle dependence of the parameter A. This explains how and why the angular dependence of the sputtering yield changes significantly with increasing E/n. These results are also accurately confirmed using the published measurements for polystyrene by Rading et al.

Doxycycline induced acute erosive oesophagitis and presenting as acute dysphagia.

INTRODUCTION: Drug induced oesophageal disease is common. Doxycycline is one of the commonest cause of drug induced oesophageal ulcers. The medical community often under recognizes the importance of drug induced oesophageal lesions and fails to deliver proper advice and instructions related to drug ingestion. The diagnosis is usually clinical although endoscopy is the gold standard diagnostic tool. Treatment is symptomatic with discontinuation of the drug often being sufficient. Long-term sequelae are infrequent and acute complications uncommon. CLINICAL PICTURE: A 22-year-old college student was prescribed doxycycline capsules for acne and developed dysphagia. Upper gastrointestinal endoscopy revealed acute erosive oesophagitis. TREATMENT AND OUTCOME: She was managed symptomatically with proton pump inhibitors and her dysphagia improved over a period of three days. She was discharged with proper advice regarding medication ingestion and proton pump inhibitor for four weeks. CONCLUSION: Drug induced oesophageal disease is a preventable self-limiting condition. Proper advice regarding medication ingestion is essential for prevention.

Mass spectrometry and informatics: distribution of molecules in the PubChem database and general requirements for mass accuracy in surface analysis.

Mass spectrometry is a powerful tool for the analysis and identification of substances across a broad range of technologies from proteomics and metabolomics through to surface analysis methods used for nanotechnology. A major challenge has been the development of automated methods to identify substances from the mass spectra. Public chemical databases have grown over 2 orders of magnitude in size over the past few years and have become a powerful tool in informatics approaches for identification. We analyze the popular PubChem database in terms of the population of substances with mass when resolved with typical mass spectrometer mass accuracies. We also characterize the average molecule in terms of the mass excess from nominal mass and the modal mass. It is shown, in agreement with other studies, that for the identification of unknowns a mass accuracy of around 1 ppm is required together with additional filtering using isotope patterns. This information is an essential part of a framework being developed for experimental library-free interpretation of complex molecule spectra in secondary ion mass spectrometry.

Diuretic, opiate and nitrate use in severe acidotic acute cardiogenic pulmonary oedema: analysis from the 3CPO trial.

BACKGROUND: Drug treatments for acute cardiogenic pulmonary oedema (ACPO) have not been rigorously evaluated and recent observational data suggests some agents are related to poorer outcome. AIM: We aimed to examine the effect of treatment with diuretics, nitrates and opiates on 7-day mortality, acidosis and respiratory distress in UK Emergency Department (ED) patients with severe acidotic pulmonary oedema. DESIGN: Analysis of data from the 3CPO trial; a multicentre randomized controlled trial. METHODS: Data were analysed from patients recruited with severe acidotic pulmonary oedema to the 3CPO trial in 26 UK EDs between 2003 and 2007. The effects of these treatments on 7-day mortality, improvement in acidosis (pH change between baseline and 1 h) and improvement in respiratory distress (patient measured breathlessness using a Visual Analogue Score between baseline and 1 h) were tested using univariate logistic regression analysis, and a regression model used to adjust for confounding baseline differences. RESULTS: Nitrates were given to 947/1048 (90.4%) patients, diuretics to 934/1049 (89.0%) patients and opiates to 541/1052 patients (51.4%). Adjusted analysis showed that opiate treatment was associated with less improvement in acidosis [difference in improvement in pH -0.022, 95% confidence interval (CI) -0.014 to -0.030, P < 0.001], but no difference in mortality or improvement in respiratory distress. We found no evidence that nitrate or diuretic use were associated with any difference in mortality, improvement in acidosis or respiratory distress. CONCLUSION: Opiate use is associated with less improvement in acidosis during initial treatment and may attenuate effective treatment of severe acidotic ACPO.

Organic depth profiling of a nanostructured delta layer reference material using large argon cluster ions.

Cluster ion beams have revolutionized the analysis of organic surfaces in time-of-flight secondary ion mass spectrometry and opened up new capabilities for organic depth profiling. Much effort has been devoted to understanding the capabilities and improving the performance of SF(5)(+) and C(60)(n+), which are successful for many, but not all, organic materials. Here, we explore the potential of organic depth profiling using novel argon cluster ions, Ar(500)(+) to Ar(1000)(+). We present results for an organic delta layer reference sample, consisting of ultrathin "delta" layers of Irganox 3114 (approximately 2.4 nm) embedded between thick layers of Irganox 1010 (approximately 46 or 91 nm). This indicates that, for the reference material, major benefits can be obtained with Ar cluster ions, including a constant high sputtering yield throughout a depth of approximately 390 nm, and an extremely low sputter-induced roughness of <5 nm. Although the depth resolution is currently limited by an instrumental artifact, and may not be the best attainable, these initial results strongly indicate the potential to achieve high depth resolution and suggest that Ar cluster ions may have a major role to play in the depth profiling of organic materials.

Breast cancer knowledge and screening practices: a survey of 1,000 Asian women.

INTRODUCTION: The incidence of breast cancer in Asia is rapidly rising. Knowledge and perception often influence attendance at screening programmes. However, there has not been any survey to assess the level of knowledge of breast cancer in an Asian population. Singapore has a multiracial population and is the only Asian country with a national screening programme. We conducted a survey on 1,000 women to assess their level of knowledge and screening practices. METHODS: A self-administered questionnaire was used, where one point was given for a correct answer and zero for an incorrect / "not sure" response. The maximum knowledge score was 19. The women were also surveyed for their screening practices. Points were not assigned to questions on practice. RESULTS: The response rate was 100 percent. The mean score was 11.4 and the median was 12 (range 0-19). The scores were high for general knowledge and disease progression, but poor for risk factors, screening, symptoms and treatment. Several myths and misconceptions were prevalent. Only 53 percent did regular breast self-examination (BSE), while 57 percent of women aged 40 years and above had gone for a screening mammogram. Increasing age, Malay race, lower educational level, lower socioeconomic class and not knowing anyone with breast cancer were significant independent predictors of poor knowledge. Higher educational level and knowledge scores were significant independent predictors of BSE practice and screening mammogram attendance. CONCLUSION: Knowledge affects practice. Public education is required to correct misconceptions and focus on women with poor knowledge. This would help to improve screening attendance rates.

Developing repeatable measurements for reliable analysis of molecules at surfaces using desorption electrospray ionization.

Desorption electrospray ionization (DESI) is a powerful ambient ionization technique that can provide high-sensitivity mass spectrometry information directly from surfaces at ambient pressure. Although a growing amount of research has been devoted to exploring different applications, there are few studies investigating the basic parameters and underpinning metrology. An understanding of these is crucial to develop DESI as the robust and reliable technique required for significant uptake by industry. In this work, we begin with a systematic study of the parameters affecting the repeatability, sensitivity, and rate of consumption of material with DESI. To do this we have developed a model sample consisting of a thin uniform film of controlled thickness of Rhodamine B on glass. This model sample allowed assessment of optimal sensitivity and spot shape under different conditions. In addition, it allowed us to study the surface in more detail to understand why and how each parameter affects these. Using the model sample to optimize the instrument parameters for DESI led to an absolute intensity repeatability of better than 15%, achieved over a period of 1 day. This model sample provides valuable insight into the electrospray-sample interaction and the desorption mechanism. Confocal microscopy of areas analyzed by DESI allow droplet distribution, material utilization, and spot size to be determined. Studying surface erosion also gives the erosion rate of material, analogous to the sputtering yield in secondary ion mass spectrometry. The results of the study provide a clear description that explains the differences observed with changing electrospray parameters allowing optimization of the technique, for both spatial resolution and sensitivity.

Analysis of the interface and its position in C60(n+) secondary ion mass spectrometry depth profiling.

C60(n+) ions have been shown to be extremely successful for SIMS depth profiling of a wide range of organic materials, causing significantly less degradation of the molecular information than more traditional primary ions. This work focuses on examining the definition of the interface in a C60(n+) SIMS depth profile for an organic overlayer on a wafer substrate. First it investigates the optimum method to define the organic/inorganic interface position. Variations of up to 8 nm in the interface position can arise from different definitions of the interface position in the samples investigated here. Second, it looks into the reasons behind large interfacial widths, i.e., poor depth resolution, seen in C60(n+) depth profiling. This work confirms that, for Irganox 1010 deposited on a wafer, the depth resolution at the Irganox 1010/substrate interface is directly correlated to the roughening of material. C60n+

Am I breast cancer smart? Assessing breast cancer knowledge among health professionals.

INTRODUCTION: Health professionals are a direct source of medical information to the public. Hence, it is crucial that their knowledge is accurate and aids in building awareness. Our aim was to ascertain the level of breast cancer knowledge and screening practices among nurses in a general hospital. METHODS: Between January and April 2004, all registered nurses in a general hospital were surveyed by a self-administered questionnaire for their knowledge of breast cancer and screening practices. One point was given for a correct knowledge answer and zero for wrong/"not sure" answer. The maximum knowledge score was 19. RESULTS: There were 716 (79.4 percent) respondents. The median score was 16 (range 2-19). The scores were high for general knowledge and natural disease progression, fair for knowledge of symptoms and treatment, but dropped when it came to knowledge of risk factors and screening. Nurses also held several common misconceptions held by the public. Those who had managed breast cancer patients had higher total scores (15.7). Only 63 percent did regular breast self-examination (BSE) and only 35 percent had gone for a screening mammogram. Chinese nurses who had managed breast cancer patients were more likely to do regular BSE. CONCLUSION: Nurses working in a general hospital had good knowledge of breast cancer progression, average understanding of symptoms and treatment, but lacked knowledge in risk factors and screening. They had low BSE and mammographic screening rates. Experience in managing breast cancer patients improved their knowledge and practices.

TOF-SIMS: accurate mass scale calibration.

A study is presented of the factors affecting the calibration of the mass scale in time-of-flight secondary ion mass spectrometry (TOF-SIMS). At the present time, TOF-SIMS analysts using local calibration procedures achieve a rather poor relative mass accuracy of only 150 ppm for large molecules (647 u) whereas for smaller fragments of <200 u this figure only improves to 60 ppm. The instrumental stability is 1 ppm and better than 10 ppm is necessary for unique identification of species. The above experimental uncertainty can lead to unnecessary confusion where peaks are wrongly identified or peaks are ambiguously assigned. Here we study, in detail, the instrumental parameters of a popular single stage reflection TOF-SIMS instrument with ion trajectory calculations using SIMION. The effect of the ion kinetic energy, emission angle, and other instrumental operating parameters on the measured peak position are determined. This shows clearly why molecular and atomic ions have different relative peak positions and the need for an aperture to restrict ions at large emission angles. These data provide the basis for a coherent procedure for optimizing the settings for accurate mass calibration and rules by which calibrations for inorganics and organics may be incorporated. This leads to a new generic set of ions for mass calibration that improves the mass accuracy in our interlaboratory study by a factor of 5. A calibration protocol is developed, which gives a relative mass accuracy of better than 10 ppm for masses up to 140 u. The effects of extrapolation beyond the calibration range are discussed and a recommended procedure is given to ensure that accurate mass is achieved within a selectable uncertainty for large molecules. Additionally, we can alternatively operate our instrument in a regime with good energy discrimination (i.e., poor energy compensation) to study the fragmented energies of molecules. This leads to data that support previous concepts developed in G-SIMS.

The use of the vacuum erection device in the management of erectile impotence.

A retrospective survey was conducted to assess the use, efficacy and acceptance of the Vacuum Erection Device (VED) among 60 impotent men not satisfied with intracavernosal injection therapy. Forty three (72%) men filled out the questionnaires. Thirty nine (81%) of the men abandoned the device, the main reason being that 'it did not work'. One possible explanation for this was patient selection, testing the VED on men who had previously found injection therapy unsatisfactory. Patients' attitudes to the device were unfavourable overall. Sixty four percent of men had at least one minor side effect using the VED, the most common being discomfort. The role of the partner for men using this form of treatment is unresolved. In this study, the VED was no more effective than injections in overcoming erectile dysfunction, but the relative advantages of either treatment needs to be addressed in controlled clinical trials.

Concordance and precision of dual X-ray absorptiometry with a 10 s scan.

Development of dual energy X-ray absorptiometry (DXA) scanners with multidetector array technology has resulted in greatly shortened scanning times. The Hologic QDR-4500 includes an ultrafast (10 s) "turbo" scan mode recommended by the manufacturer for fast screening studies or as an aid to positioning the patient prior to scanning using the normal fast (30 s), medium (1 min) or high definition (2 min) modes. The suitability of the turbo mode for use in routine clinical studies was assessed by examining the concordance of bone mineral density (BMD) measurements obtained in this mode with measurements obtained using the three normal scanning modes. Studies in 151 female patients showed statistically significant discrepancies in four out of the six scan sites studied with systematic differences of 2.9% and 3.1% being observed for the posteroanterior (PA) spine and intertrochanteric region of the hip, respectively. In vivo precision for the 10 s scan found by performing duplicate measurements on 37 patients had a coefficient of variation of 1.3% for PA spine and 2.5% for femoral neck BMD. An investigation of the dependence of precision on body mass index (BMI) shows that the precision of spine and hip BMD was adversely affected with increasing BMI but the trend was statistically significant only in the spine. It was concluded that turbo mode scans are acceptable for routine clinical studies of the spine and hip but should not be used for longitudinal studies or patients with BMI greater than 30 kg m-2.