EPIC: an evaluation of the psychological impact of early-phase clinical trials in cancer patients.

BACKGROUND: Anxiety and depression in patients with cancer is associated with decreased quality of life and increased morbidity and mortality. However, these are often overlooked and untreated. Early-phase clinical trials (EPCTs) recruit patients with advanced cancers who frequently lack future treatment options, which may lead to increased anxiety and depression. Despite this, EPCTs do not routinely consider psychological screening for patients. PATIENTS AND METHODS: This prospective observational study explored levels of anxiety and depression alongside impact of trial participation in the context of EPCTs. The Hospital Anxiety and Depression Scale and the Brief Illness Perceptions Questionnaire were completed at the point of EPCT consent, the end of screening and at pre-specified time points thereafter. RESULTS: Sixty-four patients (median age 56 years; median Eastern Cooperative Oncology Group performance status 1) were recruited. At consent, 57 patients returned questionnaires; 39% reported clinically relevant levels of anxiety whilst 18% reported clinically relevant levels of depression. Sixty-three percent of patients experiencing psychological distress had never previously reported this. Males were more likely to be depressed (P = 0.037) and females were more likely to be anxious (P = 0.011). Changes in anxiety or depression were observed after trial enrolment on an individual level, but not significant on a population level. CONCLUSIONS: Patients on EPCTs are at an increased risk of anxiety and depression but may not seek relevant support. Sites offering EPCTs should consider including psychological screening to encourage a more holistic approach to cancer care and consider the sex of individuals when tailoring psychological support to meet specific needs.

Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile dermatomyositis among paediatric dermatologists, rheumatologists and neurologists.

BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be reliable and valid outcome measures to assess cutaneous disease in adult dermatomyositis (DM) and juvenile DM (JDM), respectively. OBJECTIVES: This study compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric rheumatologists and paediatric neurologists in patients with JDM. METHODS: Five paediatric dermatologists, five paediatric rheumatologists and five paediatric neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra-rater reliability, construct validity and completion time were compared. RESULTS: Inter-rater reliability for CDASI activity and damage scores was good to moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists. The inter-rater reliability for CAT-BM activity scores was moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists and poor across all specialties for damage scores. Intra-rater reliability for the CDASI and CAT-BM activity and damage scores was moderate to excellent for paediatric dermatologists, rheumatologists and neurologists. Strong associations were found between skin PGA activity and damage scores and CDASI or CAT-BM activity and damage scores, respectively (P < 0·002). The CDASI had a mean completion time of 5·4 min compared with that for the CAT-BM of 3·1 min. CONCLUSIONS: Our data confirm the reliability of the CDASI activity and damage scores and the CAT-BM activity scores when used by paediatric dermatologists and rheumatologists in assessing JDM. Significant variation existed in the paediatric neurologists' scores.

Observation of Mollow Triplets with Tunable Interactions in Double Lambda Systems of Individual Hole Spins.

Although individual spins in quantum dots have been studied extensively as qubits, their investigation under strong resonant driving in the scope of accessing Mollow physics is still an open question. Here, we have grown high quality positively charged quantum dots embedded in a planar microcavity that enable enhanced light-matter interactions. Under a strong magnetic field in the Voigt configuration, individual positively charged quantum dots provide a double lambda level structure. Using a combination of above-band and resonant excitation, we observe the formation of Mollow triplets on all optical transitions. We find that when the strong resonant drive power is used to tune the Mollow-triplet lines through each other, we observe anticrossings. We also demonstrate that the interaction that gives rise to the anticrossings can be controlled in strength by tuning the polarization of the resonant laser drive. Quantum-optical modeling of our system fully captures the experimentally observed spectra and provides insight on the complicated level structure that results from the strong driving of the double lambda system.

Chemical Considerations for an Updated National Assessment of Brackish Groundwater Resources.

Brackish groundwater (BGW) is increasingly used for water supplies where fresh water is scarce, but the distribution and availability of such resources have not been characterized at the national scale in the United States since the 1960s. Apart from its distribution and accessibility, BGW usability is a function of the chemical requirements of the intended use, chemical characteristics of the resource, and treatment options to make the resource compatible with the use. Here, we discuss relations between these three chemical factors using national-scale examples and local case studies. In a preliminary compilation of BGW data in the United States, five water types accounted for the major-ion composition of 70% of samples. PHREEQC calculations indicate that 57-77% of samples were oversaturated with respect to barite, calcite, or chalcedony. In the study, 5-14% of samples had concentrations of arsenic, fluoride, nitrate, or uranium that exceeded drinking-water standards. In case studies of the potential use of BGW for drinking water, irrigation, and hydraulic fracturing, PHREEQC simulations of a hypothetical treatment process resembling reverse osmosis (RO) showed that BGW had the potential to form various assemblages of mineral deposits (scale) during treatment that could adversely affect RO membranes. Speciation calculations showed that most boron in the irrigation example occurred as boric acid, which has relatively low removal efficiency by RO. Results of this preliminary study indicate that effective national or regional assessments of BGW resources should include geochemical characterizations that are guided in part by specific use and treatment requirements.

Quality and age of shallow groundwater in the Bakken Formation production area, Williston Basin, Montana and North Dakota.

The quality and age of shallow groundwater in the Bakken Formation production area were characterized using data from 30 randomly distributed domestic wells screened in the upper Fort Union Formation. Comparison of inorganic and organic chemical concentrations to health based drinking-water standards, correlation analysis of concentrations with oil and gas well locations, and isotopic data give no indication that energy-development activities affected groundwater quality. It is important, however, to consider these results in the context of groundwater age. Most samples were recharged before the early 1950s and had 14C ages ranging from <1000 to >30,000 years. Thus, domestic wells may not be as well suited for detecting contamination associated with recent surface spills as shallower wells screened near the water table. Old groundwater could be contaminated directly by recent subsurface leaks from imperfectly cemented oil and gas wells, but horizontal groundwater velocities calculated from 14C ages imply that the contaminants would still be less than 0.5 km from their source. For the wells sampled in this study, the median distance to the nearest oil and gas well was 4.6 km. Because of the slow velocities, a long-term commitment to groundwater monitoring in the upper Fort Union Formation is needed to assess the effects of energy development on groundwater quality. In conjunction with that effort, monitoring could be done closer to energy-development activities to increase the likelihood of early detection of groundwater contamination if it did occur.

Alkalinity conversion of bauxite refinery residues by neutralization.

Red mud remains the largest environmental issue for the alumina industry due to its high pH (>13), fine-grained nature (>90% is <10 microm), elevated sodium concentration (>50 g/kg), and soluble alkalinity (approximately 30 g/kg as equivalent CaCO(3)), which reduce the transport and reuse options of red mud. The neutralization of red mud provides potential reuse options because neutralization lowers pH, increases grain-size (e.g., coagulation), and precipitates or converts alkalinity. This paper investigates the geochemistry of 3 treatments of a red mud to affect neutralization and potentially convert materials from a waste material to a resource. This study investigates two commonly used neutralization techniques, a CO(2)-neutralized red mud (CNRM), a Basecon-neutralized red mud (Basecon), and a more novel approach of a CO(2)-neutralization followed by a Basecon-neutralization (Hybrid) to understand the effects that these treatments have on neutralization process. Data indicate that the neutralization techniques form two distinct geochemical groups when discriminated on total alkalinity alone, that is treatments with, and treatments without alkalinity precipitation. However, each treatment has distinct alkalinity speciation (hydroxide-dominant or carbonate/bicarbonate dominant) and residual Ca, Mg and Al in the treatment solution. Similarly, solids produced differ in their reaction pH and ANC, and contrary pH and ANC, a contrary to other studies, Dawsonite was not seen to precipitate during any neutralization. However, despite this approximately 17 g/kg CO(2) was sequestered during CNRM and hybrid neutralizations and all treatments increased either the transport or reuse options of red mud in some way.

Redox processes and water quality of selected principal aquifer systems.

Reduction/oxidation (redox) conditions in 15 principal aquifer (PA) systems of the United States, and their impact on several water quality issues, were assessed from a large data base collected by the National Water-Quality Assessment Program of the USGS. The logic of these assessments was based on the observed ecological succession of electron acceptors such as dissolved oxygen, nitrate, and sulfate and threshold concentrations of these substrates needed to support active microbial metabolism. Similarly, the utilization of solid-phase electron acceptors such as Mn(IV) and Fe(III) is indicated by the production of dissolved manganese and iron. An internally consistent set of threshold concentration criteria was developed and applied to a large data set of 1692 water samples from the PAs to assess ambient redox conditions. The indicated redox conditions then were related to the occurrence of selected natural (arsenic) and anthropogenic (nitrate and volatile organic compounds) contaminants in ground water. For the natural and anthropogenic contaminants assessed in this study, considering redox conditions as defined by this framework of redox indicator species and threshold concentrations explained many water quality trends observed at a regional scale. An important finding of this study was that samples indicating mixed redox processes provide information on redox heterogeneity that is useful for assessing common water quality issues. Given the interpretive power of the redox framework and given that it is relatively inexpensive and easy to measure the chemical parameters included in the framework, those parameters should be included in routine water quality monitoring programs whenever possible.

The relationship between the orientation of the glenoid and tears of the rotator cuff.

Our aim was to determine the most repeatable three-dimensional measurement of glenoid orientation and to compare it between shoulders with intact and torn rotator cuffs. Our null hypothesis was that glenoid orientation in the scapulae of shoulders with a full-thickness tear of the rotator cuff was the same as that in shoulders with an intact rotator cuff. We studied 24 shoulders in cadavers, 12 with an intact rotator cuff and 12 with a full-thickness tear. Two different observers used a three-dimensional digitising system to measure glenoid orientation in the scapular plane (ie glenoid inclination) using six different techniques. Glenoid version was also measured. The overall precision of the measurements revealed an error of less than 0.6 degrees. Intraobserver reliability (correlation coefficients of 0.990 and 0.984 for each observer) and interobserver reliability (correlation coefficient of 0.985) were highest for measurement of glenoid inclination based on the angle obtained from a line connecting the superior and inferior points of the glenoid and that connecting the most superior point of the glenoid and the most superior point on the body of the scapula. There were no differences in glenoid inclination (p = 0.34) or glenoid version (p = 0.12) in scapulae from shoulders with an intact rotator cuff and those with a full-thickness tear. Abnormal glenoid orientation was not present in shoulders with a torn rotator cuff.

Regional patterns in the isotopic composition of natural and anthropogenic nitrate in groundwater, High Plains, U.S.A.

Mobilization of natural nitrate (NO3-) deposits in the subsoil by irrigation water in arid and semiarid regions has the potential to produce large groundwater NO3-concentrations. The use of isotopes to distinguish between natural and anthropogenic NO3- sources in these settings could be complicated by the wide range in delta15N values of natural NO3-. An approximately 10 000 year record of paleorecharge from the regionally extensive High Plains aquifer indicates that delta15N values for NO3- derived from natural sources ranged from 1.3 to 12.3 per thousand and increased systematically from the northern to the southern High Plains. This collective range in delta15N values spans the range that might be interpreted as evidence for fertilizer and animal-waste sources of NO3-; however, the delta15N values for NO3- in modern recharge (< 50 years) under irrigated fields were, for the most part, distinctly different from those of paleorecharge when viewed in the overall regional context. An inverse relation was observed between the delta15N[NO3-] values and the NO3-/Cl- ratios in paleorecharge that is qualitatively consistent with fractionating losses of N increasing from north to south in the High Plains. N and O isotope data for NO3- are consistent with both NH3 volatilization and denitrification, having contributed to fractionating losses of N prior to recharge. The relative importance of different isotope fractionating processes may be influenced by regional climate patterns as well as by local variation in soils, vegetation, topography, and moisture conditions.

Thermal and cold neutron phase-contrast radiography.

In this paper, we will discuss a phase-contrast imaging method that avoids the complications of interferometry to provide phase contrast in weakly absorbing samples. A transversely coherent neutron beam is used with the traditional radiography scheme. Images taken with this scheme show dramatic intensity variations due to sharp changes in the neutron wave refractive index. With some numerical processing these images may be used to reconstruct a quantitative phase radiograph of specimens imaged with this technique.

Quantitative phase-amplitude microscopy. III. The effects of noise.

We explore the effect of noise on images obtained using quantitative phase-amplitude microscopy - a new microscopy technique based on the determination of phase from the intensity evolution of propagating radiation. We compare the predictions with experimental results and also propose an approach that allows good-quality quantitative phase retrieval to be obtained even for very noisy data.

Quantitative phase radiography with polychromatic neutrons.

We develop and experimentally demonstrate a formalism that allows accurate phase imaging using neutron sources producing highly polychromatic beams. The results of measurements from a rectangular block of silicon compare favorably with theoretical simulations based upon the known composition and geometry of the block. The increased flux and reduced exposure times will permit a simple extension of the technique to tomographic phase imaging.

[Biomechanical tests for type II SLAP lesions of the shoulder joint before and after arthroscopic repair]. / Biomechanische Untersuchungen zur Typ-2-SLAP-Läsion am Schultergelenk vor und nach arthroskopischen Repair.

Superior labral anterior-to-posterior (SLAP) lesions can cause shoulder pain partly by causing glenohumeral instability. The purpose of this study was to examine the effect of a simulated type II SLAP lesion and subsequent repair on glenohumeral translation of the vented shoulder. In eight cadaver joints, a robotic/UFS testing system was used to measure joint translation by applying an anterior, posterior, or inferior load of 50 N to each shoulder. The "apprehension tests" for anterior and posterior instability were simulated by applying an anterior load of 50 N with an external rotation torque of 3 Nm or a posterior load of 50 N with an internal rotation torque of 3 Nm. Each loading condition was applied at 30 degrees and 60 degrees of glenohumeral abduction with a constant joint compressive load (44 N) to the intact, simulated SLAP lesion, and repaired shoulder. Repair of the type II SLAP was then performed by placing a Suretac through the labrum both anterior and posterior to the biceps anchor and testing was repeated. ANOVA was used to compare translation of the intact joint, the joint after the type II SLAP lesion had been simulated, and after repair. At 30 degrees of abduction, anterior translation of the intact vented shoulder joint from anterior loading was 18.7+/-8.5 mm and increased to 26.2+/-6.5 mm after simulation of the type II SLAP lesion ( p< or =0.05). The arthroscopic repair did not restore anterior translation (23.9+/-8.6 mm) to the same degree as the intact joint ( p> or =0.05). At 60 degrees of abduction, anterior translation of 16.6+/-9.6mm in the intact joint was not significantly increased at 19.4+/-10.1 after simulation of the type II SLAP lesion ( p=0.0527). AP loading also resulted in inferior translation. At 30 degrees of abduction it was 3.8+/-4.0 mm in the intact joint and increased to 8.5+/-5.4 mm after the type II SLAP lesion ( p< or =0.05. After repair the inferior translation decreased significantly to 6.7+/-5.3 mm ( p< or =0.05). Although inferior translations were less at 60 degrees of abduction, results were similar to those at 30 degrees after repair. There were no significant increases in translation after SI/AP combined external rotation torque or posterior-anterior combined internal rotation torque loading. In this study the repair of a type II SLAP lesion only partially restored translations to the same degree as an intact vented shoulder joint. Therefore, improved repair techniques or an anteroinferior capsulolabral procedure in addition to the type II SLAP lesion repair might be needed to restore normal joint function.

Measurement of the spatial coherence function of undulator radiation using a phase mask.

A measurement of the horizontal coherence function of 7.9 keV radiation from an undulator beam line at the Advanced Photon Source is reported. X-ray diffraction from a phase-shifting mask was used, and the coherence function was measured as a function of the width of beam-conditioning slits in the beam line. The coherence distribution is found to be best described by a Lorentzian function.

Colorectal cancer screening issues: a role for CT colonography?

Colorectal cancer is the third most common cancer in the United States and will cause 56,700 deaths in 2001, despite the availability of screening tests capable of detecting the disease at earlier stages and reducing mortality. This article reviews the natural history of colorectal cancer, common risk factors and prevention strategies, and the strengths, limitations, and cost effectiveness of available screening tests. Although reminders to undergo colorectal cancer screening have become commonplace in the popular media, compliance with screening guidelines remains poor. Although still an unproven technology for widespread screening, computed tomographic (CT) colonography has several attractive characteristics for a screening test. For example, CT scanners are widely available, in contrast to limited numbers of gastroenterologists and radiologists' declining skill and interest in barium enema examinations. Also, patients may be less reluctant to undergo CT colonography than screening colonoscopy. Development of virtual bowel cleansing could further increase compliance and thereby reduce mortality from colorectal cancer. Other articles in this Feature Section discuss technical details of CT colonography and its methodologic challenges.

Quantitative phase-amplitude microscopy II: differential interference contrast imaging for biological TEM.

Although phase contrast microscopy is widespread in optical microscopy, it has not been as widely adopted in transmission electron microscopy (TEM), which has therefore to a large extent relied on staining techniques to yield sufficient contrast. Those methods of phase contrast that are used in biological electron microscopy have been limited by factors such as the need for small phase shifts in very thin samples, the requirement for difficult experimental conditions, or the use of complex data analysis methods. We here demonstrate a simple method for quantitative TEM phase microscopy that is suitable for large phase shifts and requires only two images. We present a TEM phase image of unstained Radula sp. (liverwort spore). We show how the image may be transformed into the differential interference contrast image format familiar from optical microscopy. The phase images contain features not visible with the other imaging modalities. The resulting technique should permit phase contrast TEM to be performed almost as readily as phase contrast optical microscopy.

The pore structure in processed Victorian Brown coal.

Changes in the pore structure of Victorian Brown coal when upgraded with heated gases under pressure are investigated. We show that the results obtained from ultra-small-angle neutron scattering (USANS) measurements agree with previous results using small-angle X-ray scattering results but that USANS may also be used to investigate the meso porosity. Findings from small-angle scattering are confirmed using electron microscopy. We also show evidence from electron diffraction that thermal conditions within the brown coals during the upgrade procedure may be far more extreme than previously thought.

The effects of tibial rotation on the patellofemoral joint: assessment of the changes in in situ strain in the peripatellar retinaculum and the patellofemoral contact pressures and areas.

The objective of this study was to determine the effects of tibial rotation on in situ strain in the peripatellar retinaculum and patellofemoral contact pressures and areas. Patellofemoral joint biomechanics demonstrate a strong correlation with the etiology of patellofemoral disorders, such as chondromalacia, and are significantly influenced by tibial rotation. Six human cadaveric knees were used along with a patellofemoral joint testing jig that permits physiological loading of the knee extensor muscles. Patellofemoral contact pressures and areas were measured with a Fuji pressure-sensitive film, and the changes in in situ strain in the peripatellar retinaculum were measured with four differential variable reluctance transducers. Tibial rotation had a significant effect on patellofemoral joint biomechanics. The data showed an inverse relationship between increasing knee flexion angles and the change in patellofemoral contact pressures and in situ strain with tibial rotation. At higher knee flexion angles, the patella is well-seated in the trochlear groove and the function of the peripatellar retinaculum is minimized and less affected by tibial rotations.

Potential influence of acute CT on inpatient costs in patients with ischemic stroke.

RATIONALE AND OBJECTIVES: Patients presenting with ischemic brain symptoms have widely variable outcomes dependent to some degree on the pathologic basis of their stroke syndrome. The purpose of this study was to determine the cost implications of the emergency use of a computed tomographic (CT) protocol comprising unenhanced CT, head and neck CT angiography, and whole-brain CT perfusion. MATERIALS AND METHODS: By using a retrospective patient database from a tertiary care facility and publicly available cost data, the authors derived the potential savings from the use of CT angiography. CT perfusion, or both at hospital arrival by means of a cost model. The cost of the CT angiography-CT perfusion protocol was determined from Medicare reimbursement rates and compared with that of traditional imaging protocols. Cost savings were estimated as a decrease in the length of stay for most stroke patients, whereas the most benign (lacunar) strokes were assumed to be managed in a non-acute setting. Misdiagnosis cost (erroneously not admitting a patient with nonlacunar stroke) was calculated as the cost of a severe complication. Sensitivity testing included varying the percentage of misdiagnosed patients and admitting patients with lacunar stroke. RESULTS: The nationwide net savings that would result from the adoption of the CT angiography-CT perfusion protocol are in the $1.2 billion range (-$154 million to $2.1 billion) when patients with lacunar strokes are treated nonacutely and $1.8 billion when those patients are admitted for acute care. CONCLUSION: The results demonstrate the potential effect of implementing a CT angiography-CT perfusion protocol. In particular, prompt CT angiography-CT perfusion imaging could have an effect on the cost of acute care in the treatment of stroke.