Ties between event times and jump times in the Cox model.

Methods for dealing with tied event times in the Cox proportional hazards model are well developed. Also, the partial likelihood provides a natural way to handle covariates that change over time. However, ties between event times and the times that discrete time-varying covariates change have not been systematically studied in the literature. In this article, we discuss the default behavior of current software and propose some simple methods for dealing with such ties. A simulation study shows that the default behavior of current software can lead to biased estimates of the coefficient of a binary time-varying covariate and that two proposed methods (Random Jitter and Equally Weighted) reduce estimation bias. The proposed methods can be easily implemented with existing software. The methods are illustrated on the well-known Stanford heart transplant data and data from a study on intimate partner violence and smoking.

Image quality evaluation of breast tomosynthesis with synchrotron radiation.

PURPOSE: This study investigates the image quality of tomosynthesis slices obtained from several acquisition sets with synchrotron radiation using a breast phantom incorporating details that mimic various breast lesions, in a heterogeneous background. METHODS: A complex Breast phantom (MAMMAX) with a heterogeneous background and thickness that corresponds to 4.5 cm compressed breast with an average composition of 50% adipose and 50% glandular tissue was assembled using two commercial phantoms. Projection images using acquisition arcs of 24°, 32°, 40°, 48°, and 56° at incident energy of 17 keV were obtained from the phantom with the synchrotron radiation for medical physics beamline at ELETTRA Synchrotron Light Laboratory. The total mean glandular dose was set equal to 2.5 mGy. Tomograms were reconstructed with simple multiple projection algorithm (MPA) and filtered MPA. In the latter case, a median filter, a sinc filter, and a combination of those two filters were applied on the experimental data prior to MPA reconstruction. Visual inspection, contrast to noise ratio, contrast, and artifact spread function were the figures of merit used in the evaluation of the visualisation and detection of low- and high-contrast breast features, as a function of the reconstruction algorithm and acquisition arc. To study the benefits of using monochromatic beams, single projection images at incident energies ranging from 14 to 27 keV were acquired with the same phantom and weighted to synthesize polychromatic images at a typical incident x-ray spectrum with W target. RESULTS: Filters were optimised to reconstruct features with different attenuation characteristics and dimensions. In the case of 6 mm low-contrast details, improved visual appearance as well as higher contrast to noise ratio and contrast values were observed for the two filtered MPA algorithms that exploit the sinc filter. These features are better visualized at extended arc length, as the acquisition arc of 56° with 15 projection images demonstrates the highest image reconstruction quality. For microcalcifications, filtered MPA implemented with a combination of median and sinc filters indicates better feature appearance due to efficient suppression of background tissue. The image quality of these features is less sensitive to the acquisition arc. Calcifications with size ranging from 170 to 500 µm, like the ones presently studied, are well identified and visualized for all arcs used. The comparison of single projection images obtained under different beam conditions showed that the use of monochromatic beam can produce an image with higher contrast and contrast to noise ratio compared to an image corresponding to a polychromatic beam even when the latter is acquired with double incident exposure. CONCLUSIONS: Filter optimization in respect to the type of feature characteristics is important before the reconstruction. The MPA combined with median and sinc filters results in improved reconstruction of microcalcifications and low-contrast features. The latter are better visualized at extended arc length, while microcalcifications are less sensitive to this acquisition parameter. Use of monochromatic beams may result in tomographic images with higher contrast acquired at lower incident exposures.

Diagnosis and management of acute kidney injury: deficiencies in the knowledge base of non-specialist, trainee medical staff.

Enhanced education has been recommended to improve non-specialist management of acute kidney injury (AKI). However, the extent of any gaps in knowledge has yet to be defined fully. The aim of this study was to assess understanding of trainee doctors in the prevention, diagnosis and initial management of AKI. An anonymised questionnaire was completed by hospital-based trainees across Newcastle Renal Unit's catchment area. Responses were evaluated against a panel of pre-defined ideal answers. The median score was 9.5 out of 20 (n = 146; range 0-17) and was lower in more junior trainees. Fifty percent of trainees could not define AKI, 30% could not name more than two risk factors for AKI and 37% could not name even one indication for renal referral. These serious gaps in knowledge highlight the need for enhanced education aimed at all training grades. Organisational changes may also be required to optimise patient safety.

Evaluation of digital breast tomosynthesis reconstruction algorithms using synchrotron radiation in standard geometry.

PURPOSE: In this article, the image quality of reconstructed volumes by four algorithms for digital tomosynthesis, applied in the case of breast, is investigated using synchrotron radiation. METHODS: An angular data set of 21 images of a complex phantom with heterogeneous tissue-mimicking background was obtained using the SYRMEP beamline at ELETTRA Synchrotron Light Laboratory, Trieste, Italy. The irradiated part was reconstructed using the multiple projection algorithm (MPA) and the filtered backprojection with ramp followed by hamming windows (FBR-RH) and filtered backprojection with ramp (FBP-R). Additionally, an algorithm for reducing the noise in reconstructed planes based on noise mask subtraction from the planes of the originally reconstructed volume using MPA (MPA-NM) has been further developed. The reconstruction techniques were evaluated in terms of calculations and comparison of the contrast-to-noise ratio (CNR) and artifact spread function. RESULTS: It was found that the MPA-NM resulted in higher CNR, comparable with the CNR of FBP-RH for high contrast details. Low contrast objects are well visualized and characterized by high CNR using the simple MPA and the MPA-NM. In addition, the image quality of the reconstructed features in terms of CNR and visual appearance as a function of the initial number of projection images and the reconstruction arc was carried out. Slices reconstructed with more input projection images result in less reconstruction artifacts and higher detail CNR, while those reconstructed from projection images acquired in reduced angular range causes pronounced streak artifacts. CONCLUSIONS: Of the reconstruction algorithms implemented, the MPA-NM and MPA are a good choice for detecting low contrast objects, while the FBP-RH, FBP-R, and MPA-NM provide high CNR and well outlined edges in case of microcalcifications.

Predictors of mental health and academic outcomes in first-year university students: Identifying prevention and early-intervention targets.

BACKGROUND: Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts. AIMS: To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes. METHOD: Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders. RESULTS: In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being. CONCLUSIONS: Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.

Correlation of energy dispersive diffraction signatures and microCT of small breast tissue samples with pathological analysis.

Identification of specific tissue types in conventional mammographic examinations is extremely limited. However, the use of x-ray diffraction effects during imaging has the potential to characterize the tissue types present due to the fact that each tissue type produces its own unique diffraction signature. Nevertheless, the analysis and categorization of these diffraction signatures by tissue type can be hampered by the inhomogeneous nature of breast tissue, leading to categorization errors where several types are present. This work aims to reduce sample categorization errors by combining spectral diffraction signature collection with sample imaging, giving more detailed data on the composition of each sample. Diffraction microCT was carried out on 19 unfixed breast tissue samples using an energy resolving translate-rotate CT system. High-resolution transmission microCT images were also recorded for comparison and sample composition analysis. Following imaging, the samples were subjected to histopathological analysis. Reconstructing on various momentum transfer regions allows different tissue types to be identified in the diffraction images. Results show a correlation between measured x-ray diffraction images and stained histopathological tissue sections. X-ray diffraction signatures generated from the measured data were categorized and analysed, with a t-test indicating that they have the potential for use in tissue type identification.

Effects of digoxin on acute, atrial fibrillation-induced changes in atrial refractoriness.

BACKGROUND: Atrial fibrillation (AF) shortens the atrial effective refractory period (ERP) and predisposes to further episodes of AF. The acute changes in atrial refractoriness may be related to tachycardia-induced intracellular calcium overload. The purpose of this study was to determine whether digoxin, which increases intracellular calcium, potentiates the acute effects of AF on atrial refractoriness in humans. METHODS AND RESULTS: In 38 healthy adults, atrial ERP was measured at basic drive cycle lengths (BDCLs) of 350 and 500 ms after autonomic blockade. Nineteen patients had been treated with digoxin for 2 weeks. After a several-minute episode of AF, atrial ERP was measured serially at alternating BDCLs. Compared with pre-AF ERPs, the first post-AF ERPs were significantly shorter in both the digoxin and the control groups (P:<0.001). The post-AF ERP at a BDCL of 350 ms shortened to a greater degree in the digoxin group (37+/-16 ms) than in the control group (20+/-13 ms, P:<0.001); similar changes occurred at a BDCL of 500 ms. During post-AF determinations of the atrial ERP, secondary AF episodes occurred significantly more often in the digoxin group (32% versus 16%; P:<0. 04). CONCLUSIONS: After a brief episode of AF, digoxin augments the shortening that occurs in atrial refractoriness and predisposes to the reinduction of AF. These effects occur in the setting of autonomic blockade and therefore are more likely to be due to the effects of digoxin on intracellular calcium than to its vagotonic effects.

Utilization of health care services in patients with severe obstructive sleep apnea.

We compared the health care utilization of 97 obese patients diagnosed with obstructive sleep apnea (OSA) and 97 matched control subjects. Over a 2-year period that ended 2 years prior to initial diagnosis, the OSA group had 251 nights in hospital, compared to 90 nights for the control group. During the same 2-year period, total expenditures from physician claims were $82,238 (Canadian dollars) in the OSA patients versus $41,018 in the control group (p < 0.01). Depending upon which assumptions one uses for the calculation of hospital costs, during the same 2-year period, the 97 OSA patients utilized between $100,000 and $200,000 more in services than their control counterparts. We conclude that sleep apnea patients are already heavy consumers of health care services prior to any specific evaluation and treatment for apnea.

A Monte Carlo study of multiple scatter effects in Compton scatter densitometry.

The contribution of multiple scatter to the measured signal in x- and gamma-ray Compton scatter densitometry has been investigated theoretically by the use of Monte Carlo techniques to follow individual photon life histories. A three component phantom was employed in the computer model to simulate the patient at three examination sites; the radius/ulna, the femoral neck, and the lumbar spine. Monoenergetic radiation beams of 60- and 100-keV photons and polyenergetic x-ray spectra of 100 and 140 kVp were used. Scattered events were detected over 360 degrees and classified according to their origin and frequency of scatter. The single scatter in bone to multiple scatter ratio was studied as an indication of the signal-to-noise ratio and this was found to vary with phantom size but was independent of photon energy. Correction factors to be used in a clinical densitometer to account for the inclusion of multiple scatter events were computed. These were found to be 0.65-0.58 at the optimum scattering angles for the phantoms considered.

A novel method for producing x-ray test objects and phantoms.

A novel method for producing customized x-ray test objects and clinically realistic phantoms has been developed. Test objects can be created with a drawing software package and the digital images can be printed on a standard inkjet printer but using potassium iodide solution in place of the cartridge's ink. The reproducibility and the consistency, the limiting spatial resolution, the uniformity as well as the potassium iodide thickness per print have been evaluated. The relationship between the number of prints, grey levels and the radiation contrast was investigated and quantified. A copy of the Leeds TO10 contrast detail test object was printed and the x-ray images of the Leeds TO10 and of the printed Leeds TO10 were compared. In addition, the potential use of this method was demonstrated by reproducing a percutaneous transluminal coronary angioplasty clinical digital image. The reproducibility and consistency of this method was found to be better than 0.1%. The limiting spatial resolution of the printer using ink was found to be 3.55 1p mm(-1) but it deteriorated when the ink was replaced with potassium iodide and as the print density increases. The uniformity across the printed area was found to be satisfactory although an artefact due to the printer was present in the x-ray images. The comparison between the Leeds TO10 and the printed Leeds TO10 gave differences less than 10%. A good agreement between the clinical image and the printed clinical image was found. In conclusion, the method is a reliable, cost-effective, flexible and alternative way for producing x-ray test objects and clinically related phantoms.

A study on radiation doses and irradiated areas in cerebral embolisation.

Patient radiation doses during interventional radiology procedures may reach the thresholds for radiation-induced skin and eye lens injuries. This study investigates the irradiated areas and doses received by patients undergoing cerebral embolisation, which is regarded as a high dose interventional radiology procedure. For each procedure the fluoroscopic and digital dose-area product (DAP), the fluoroscopic time, the total number of acquired images and entrance-skin dose (ESD) calculated by the angiographic unit were recorded. The ESD was measured by means of thermoluminescent dosimeters. In this study, the skin, eye and thyroid gland doses and the irradiated area for 30 patients were recorded. The average ESD was found to be 0.77 Gy for the posteroanterior plane and 0.78 Gy for the lateral plane. The average DAP was 48 Gy cm(2) for the posteroanterior plane and 58 Gy cm(2) for the lateral plane. The patient's average right eye dose was 60 mGy and the dose to the thyroid gland was 24 mGy. Seven patients received a dose above 1 Gy, one patient exceeded the threshold for transient erythema and one exceeded the threshold for temporary epilation. A good correlation between the DAP and the ESD for both planes has been found. The doctor's eye dose has also been measured for 17 procedures and the average dose per procedure was 0.13 mGy.

Short communication: helical computed tomography: where is the cut?

The helical scanning mode in computed tomography (CT) entails continuous table movement during image acquisition. The projections acquired in this mode will not be consistent with those in the axial scanning mode. A comparison of the helical and axial modes of scanning on the IGE HiSpeed Advantage CT system (software version ZA) has been made using a contrast-detail phantom. Differences seen between the two modes include shadow and streaking artefacts and an increase in the partial volume effect in the helical scan mode.

Optimization of scanning parameters for CT colonography.

To determine the optimal collimation, pitch and reconstruction interval for CT colonography, 10 spherical polyps between 1 mm and 10 mm diameter and made of tissue equivalent material with a CT number of 40 Hounsfield units (HU) were placed in the colon of an anthropomorphic phantom. The phantom was scanned at slice thicknesses of 3 mm, 5 mm and 7 mm and pitches of 1.0, 1.3, 1.5, 1.7 and 2.0 on an IGE Hispeed advantage system. Images were reconstructed for each scanning parameter at the minimum intervals allowed along the z-axis. The optimum scanning protocol was assessed by measuring maximum contrast between the polyp and air, sensitivity for detection of each polyp along the z-axis, and relative radiation dose. In addition, images were reviewed separately by two radiologists who graded polyp conspicuity as: 0, not seen; 1, faintly seen; 2, well seen. It was found that varying the scanning parameters caused a marked alteration in the maximum contrast between each polyp and air. For example, for the 5 mm polyp, the range of contrasts from best to worst case was 910-490 HU. It was noted that with contrasts of less than 500 HU, polyps were only faintly seen. A slice thickness of 3 mm with a pitch of 2 offers optimal polyp conspicuity with a relatively low radiation dose, we conclude that scanning parameters can be optimized for threshold contrast, radiation dose and subjective conspicuity. We propose an optimal parameter of 3 mm slice thickness and pitch 2.

The effect of decreasing mAs on image quality and patient dose in sinus CT.

The aim of this study was to determine the effect of reducing mAs on the diagnostic quality of images and the radiation dose to the orbits in patients undergoing sinus CT. We studied 40 consecutive patients undergoing paranasal sinus CT for inflammatory disease prior to functional endoscopic sinus surgery (FESS). Four groups of 10 patients were scanned at 200 mAs, 150 mAs, 100 mAs and 50 mAs, respectively. Orbital radiation dose was measured using thermoluminescent dosemeters. Images were reviewed independently by two observers who were unaware of the mAs setting used. Image quality was evaluated using a semi-quantitative scoring system for six anatomical structures. The osteomeatal complex, uncinate process, infundibulum, frontal recess, middle turbinate and optic nerve were assessed as: clearly demonstrated (2 points); demonstrated but not clearly visualized (1 point); or not seen (0 points). No significant difference was shown between any of the four groups in terms of image quality according to the scoring system used in this study. Mean radiation dose to the orbit was reduced by 77%, from 13.5 mGy at 200 mAs to 3.1 mGy at 50 mAs (p<0.05). CT of the sinuses can be performed in patients prior to FESS at greatly reduced mAs without loss of diagnostic quality of the images. This is important in reducing the radiation dose to the lens.

Pharmaceutical interventions for emotionalism after stroke.

BACKGROUND: Antidepressants may be useful in the treatment of abnormal crying associated with stroke. OBJECTIVES: To determine whether pharmaceutical treatment reduces the frequency of emotional displays in people who suffer from emotionalism after stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched June 2003). In addition we searched the following electronic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), CINAHL (1982 to September 2002), PsychINFO (1967 to September 2002), Applied Science and Technology Plus (1986 to September 2002), Arts and Humanities Index (1991 to September 2002), Biological Abstracts (1969 to September 2002), General Science Plus (1994 to September 2002), Science Citation Index (1992 to September 2002), Social Sciences Citation Index (1991 to September 2002), and Sociofile (1974 to September 2002). We searched reference lists from relevant articles and textbooks, and contacted authors of known studies and pharmaceutical companies who manufacture psychotropic medications. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, comparing psychotropic medication to placebo, in people with stroke and emotionalism (also known as emotional lability or pathological crying and laughing). DATA COLLECTION AND ANALYSIS: Data were obtained on people who no longer met criteria for emotionalism, as defined in studies, and on reduction in frequency of crying at the end of treatment. Data were not pooled because of the multiplicity of definitions and outcome measures. MAIN RESULTS: Five trials involving 103 participants were included. Four trials showed large effects of treatment: 50% reduction in emotionalism, improvements (reduction) in the frequency of compulsive laughter, and lower (better) scores on the Pathological Laughter and Crying scale. The confidence intervals were wide, however, indicating that treatment may have had only a small positive effect, or even a small negative effect (in one trial). Subgroup analysis was not performed due to the multiple methods of assessment of emotionalism within and between trials. Only one study systematically recorded and reported adverse events; no discernible difference was seen between groups. Participants allocated active treatment were more likely to leave early from trials. REVIEWERS' CONCLUSIONS: Antidepressants can reduce the frequency and severity of crying or laughing episodes. The effect do not seem specific to one drug or class of drugs. However, our conclusions must be qualified by several methodological deficiencies in the studies. More reliable data are required before recommendations can be made about the treatment of post-stroke emotionalism.

Effects of trapping on the vervet (Cercopithecus aethiops sabaeus) population in Barbados.

The effects of a 7-year trapping program on a population of vervets, Cercopithecus aethiops sabaeus, in Barbados is described. The pretrapping population was estimated at between 6,000 and 12,000 monkeys. The number trapped annually has increased from less than 200 in 1980 to almost 1,000 in 1986. Despite this, annual catch per trapping effort indicates that population abundance has remained relatively constant. However, the proportion of juveniles to adults in the population has increased markedly, largely because of an increase in the proportion of juvenile females. The data, therefore, suggest that the number of adults in the feral population has been decreasing, while that of juveniles has been increasing. The observation that adults are more vulnerable to trapping than juveniles and the possibility that juvenile survivorship has increased since trapping began may explain these trends. The change in age structure of the population toward juveniles is one explanation for the claimed increase in crop damage in Barbados at constant population size.

Beginning to work together.

Ten people met for the first time as trainees after lunch on Thursday, 4 February, 1988 at an hotel near Ipswich. They were to live and work together until teatime on Saturday. Twelve trainers joined them from late afternoon on Friday, staying on after the trainees left, until lunchtime on the Sunday. The occasion was the start of the 1988 vocational training schemes for East Anglia and North East Thames Regions. In this article, J. K. Horrocks and W. R. Allen given an account of what happened during this time, and how people felt about it.

Monitoring of intra-operative visual evoked potentials during functional endoscopic sinus surgery (FESS) under general anaesthesia.

Functional endoscopic sinus surgery (FESS) is an effective treatment for inflammatory sinus disease. The potential for major complications during FESS is high particularly under general anaesthesia. The most serious of these is injury to the eye leading to blindness. We looked at the feasibility of monitoring flash visual evoked potentials (VEP) simultaneously from both eyes during FESS. Five patients were included in this preliminary study. A haptic contact lens connected by fibreoptic cable to a photostimulator was placed on the eyes and stimulus of comparable intensity to a conventional strobe was delivered. We found that an increase in P100 latency to be an indicator of optic nerve compression. However, for this to be useful the diastolic blood pressure should not fall below 50 mmHg, the oxygen saturation should be maintained at 98 per cent and bleeding should be minimized during surgery. The changes in the amplitude of P100 was not found to be useful. While there is no substitute for learning endoscopic surgery by cadaveric dissection and supervised training we believe that in selected cases VEP monitoring can be employed with profit.

Attachment and temperament profiles among the offspring of a parent with bipolar disorder.

INTRODUCTION: Attachment is associated both with the risk of developing a mood disorder and temperamental profile. Relatively little is known about these associations in children of a parent with bipolar disorder (BD). The present study is a preliminary analysis of the association between attachment, temperament and psychopathology among high-risk offspring. METHODS: As part of an ongoing prospective cohort study, offspring from families with one parent with BD (HR) and offspring from families with unaffected parents (C) were clinically assessed using KSADS-PL format interviews annually. Validated self-report measures of perceived attachment and temperament were completed. RESULTS: Perceived attachment did not differentiate HR from C offspring and did not predict psychopathology or mood disorder in particular. However, high emotionality significantly predicted the risk of psychopathology in HR offspring, where 1 standard deviation increase in emotionality significantly increased the hazard of psychopathology by a factor of 1.36 (p=0.0009) and mood disorder by a factor of 1.24 (p=0.02). LIMITATIONS: Use of retrospective measures and low sample size for some models. CONCLUSIONS: There may be no gross abnormalities in attachment among HR compared to C offspring. It remains unclear if emotionality is a barometer of illness or a true risk factor in this population. More longitudinal research is needed to advance understanding of the influential pathways by which psychosocial risk factors impact the development of BD. This research has implications for targeted early interventions in HR youth.

Low-dose phase contrast mammography with conventional x-ray sources.

PURPOSE: To provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose. METHODS: Following the adaptation of our "edge-illumination" XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method. RESULTS: The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice. CONCLUSIONS: The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice.