Recent advances in positron emission particle tracking: a comparative review.

Positron emission particle tracking (PEPT) is a technique which allows the high-resolution, three-dimensional imaging of particulate and multiphase systems, including systems which are large, dense, and/or optically opaque, and thus difficult to study using other methodologies. In this work, we bring together researchers from the world's foremost PEPT facilities not only to give a balanced and detailed overview and review of the technique but, for the first time, provide a rigorous, direct, quantitative assessment of the relative strengths and weaknesses of all contemporary PEPT methodologies. We provide detailed explanations of the methodologies explored, including also interactive code examples allowing the reader to actively explore, edit and apply the algorithms discussed. The suite of benchmarking tests performed and described within the document is made available in an open-source repository for future researchers.

Positron Emission Particle Tracking of Granular Flows.

Positron emission particle tracking (PEPT) is a noninvasive technique capable of imaging the three-dimensional dynamics of a wide variety of powders, particles, grains, and/or fluids. The PEPT technique can track the motion of particles with high temporal and spatial resolution and can be used to study various phenomena in systems spanning a broad range of scales, geometries, and physical states. We provide an introduction to the PEPT technique, an overview of its fundamental principles and operation, and a brief review of its application to a diverse range of scientific and industrial systems.

Roller compaction of moist pharmaceutical powders.

The compression behaviour of powders during roller compaction is dominated by a number of factors, such as process conditions (roll speed, roll gap, feeding mechanisms and feeding speed) and powder properties (particle size, shape, moisture content). The moisture content affects the powder properties, such as the flowability and cohesion, but it is not clear how the moisture content will influence the powder compression behaviour during roller compaction. In this study, the effect of moisture contents on roller compaction behaviour of microcrystalline cellulose (MCC, Avicel PH102) was investigated experimentally. MCC samples of different moisture contents were prepared by mixing as-received MCC powder with different amount of water that was sprayed onto the powder bed being agitated in a rotary mixer. The flowability of these samples were evaluated in terms of the poured angle of repose and flow functions. The moist powders were then compacted using the instrumented roller compactor developed at the University of Birmingham. The flow and compression behaviour during roller compaction and the properties of produced ribbons were examined. It has been found that, as the moisture content increases, the flowability of moist MCC powders decreases and the powder becomes more cohesive. As a consequence of non-uniform flow of powder into the compaction zone induced by the friction between powder and side cheek plates, all produced ribbons have a higher density in the middle and lower densities at the edges. For the ribbons made of powders with high moisture contents, different hydration states across the ribbon width were also identified from SEM images. Moreover, it was interesting to find that these ribbons were split into two halves. This is attributed to the reduction in the mechanical strength of moist powder compacts with high moisture contents produced at high compression pressures.

The effect of lubrication on density distributions of roller compacted ribbons.

Roller compaction is a continuous dry granulation process for producing free flowing granules in order to increase the bulk density and uniformity of pharmaceutical formulations. It is a complicated process due to the diversity of powder blends and processing parameters involved. The properties of the produced ribbon are dominated by a number of factors, such as the powder properties, friction, roll speed, roll gap, feeding mechanisms and feeding speed, which consequently determine the properties of the granules (size distribution, density and flow behaviour). It is hence important to understand the influence of these factors on the ribbon properties. In this study, an instrumented roller press developed at the University of Birmingham is used to investigate the effect of lubrication on the density distribution of the ribbons. Three different cases are considered: (1) no lubrication, (2) lubricated press, in which the side cheek plates of the roller press are lubricated, and (3) lubricated powder, for which a lubricant is mixed into the powder. In addition, how the powders are fed into the entry region of the roller press and its influence on ribbon properties are also investigated. It is found that the method of feeding the powder into the roller press plays a crucial role in determining the homogeneity of the ribbon density. For the roller press used in this study, a drag angle (i.e., the angle formed when the powder is dragged into the roller press) is introduced to characterise the powder flow pattern in the feeding hopper. It is shown that a sharper drag angle results in a more heterogeneous ribbon. In addition, the average ribbon density depends upon the peak pressure and nip angle. The higher the peak pressure and nip angle are, the higher the average ribbon density is. Furthermore, the densification behaviour of the powder during roller compaction is compared to that during die compaction. It has been shown that the densification behaviour during these two processes is similar if the ribbons and the tablets have the same thickness.

The effects of high shear blending on alpha-lactose monohydrate.

alpha-Lactose monohydrate is an important pharmaceutical excipient used extensively in dry powder inhaler (DPI) formulations. The ways in which a high shear blending process affect this material have been investigated and important process parameters have been identified. Total energy input (kJ/kg), blade design and the conditions in which lactose was stored prior to blending were found to have the most significant effect on the apparent particle size distribution of the processed material, which may subsequently affect the performance of DPI formulations. The power conditions used during blending, equipment temperature and humidity of the headspace above the powder were found to be less important in this respect. Additionally, it was found that high energy blending could induce changes in the water sorption characteristics of the material, although the formation of amorphous material could not be confirmed.

The relation between granule size, granule stickiness, and torque in the high-shear granulation process.

PURPOSE: To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes. METHODS: Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipulation. Surface properties of wet granules were manipulated by coating them with talc. RESULTS: The torque-granule size relationship could not be explained by the rise in mass of the individual granules; it occurs rather through an increase in stickiness of the granules when the moisture content is increased. Obviously, the increased stickiness that causes the granules to grow also increases the torque. Increased stickiness was shown to be the result of an increased deformability of the granules at higher moisture contents, in combination with a change in surface properties. The elastic-plastic behavior (ratio of elastic to plastic deformation) was found to change at increasing moisture contents. CONCLUSIONS: Our results imply that changes in the stickiness of the granular material that may be caused by changes in composition shift the torque-size relationship. This may be of particular importance when, for example, granulation results from placebo batches are used to predict the granule size of drug-containing batches.

The effect of the amount of binder liquid on the granulation mechanisms and structure of microcrystalline cellulose granules prepared by high shear granulation.

The structure of granules changes during the high shear granulation process. The purpose of this research was to investigate the effect of the amount of binder liquid on the structure of the granules and the structural changes which occur during the granulation process, using microcrystalline cellulose (MCC) and water as the model system. The structure is the result of the granulation mechanism; therefore, conclusions can be drawn about the latter by studying the former. X-ray microtomography and scanning electron microscopy (SEM) were applied in order to visualise the densification process of granules, which were first freeze dried in order to preserve their structure. Variations in their porosity were quantified by applying image analysis to the tomography results. In order to link the granule mechanical properties to their structural differences, a micromanipulation technique was used to measure granule resistance to deformation. MCC granules granulated with 100% (w/w) water showed increased densification with time, as expected; detailed examination showed that densification is more pronounced in the core of the granule; whereas the outer part remained more porous. Increased densification reduces deformability, so that granules become more resistant to breakage. The lower deformability of the densified granules in the final stages of granulation might result in establishment of equilibrium between attrition and growth, without substantial gross breakage. On the other hand, when more water was used (125%, w/w), densification was hardly observed; the porosity of the granule core was still high even after prolonged granulation times. This may be explained by the fact that higher water content increases the ease of deformation of granules. This increased deformability led to significant granule breakage even during the final phases of the granulation process. Therefore, for these granules a final equilibrium between breakage and coalescence might be established. This also explains why more granules produced with 125% granulation liquid were composed of fragments of irregular shape. Our results establish the link between the granulation behaviour of MCC in the latter stages and the material structure of these granules, which is determined by their liquid content. The process conditions (amount of liquid) to be chosen depend largely on the final purpose for which the granular material is produced.

Panel-based pain management in primary care. a pilot study.

Although pain is an extremely common symptom presenting to primary care physicians, it frequently is not optimally managed. The purpose of this feasibility study was to develop and pilot-test an efficient, rapid assessment and management approach for pain in busy community practices. The intervention utilized the Dartmouth COOP Clinical Improvement System (DCCIS) and a telephone-based, nurse-educator intervention. Patients from four primary care practices in rural New Hampshire and Vermont were screened by mail for the presence of persistent pain. Patients with mild to severe pain were randomized to either the usual care control group (n = 383) or the intervention group (n = 320). Patients who reported pain but no psychosocial problems received a summary of identified problems and targeted educational material via mail (DCCIS). Patients who reported pain and psychosocial problems received the DCCIS intervention and calls from a nurse-educator who provided pain self-management strategies and a problem-solving approach for psychosocial problems. Post-treatment evaluation revealed that patients in the intervention group scored significantly better on the Pain, Physical, Emotional, and Social subscales of the SF-36 and on the total score of the Functional Interference Scale, as compared to a usual care control group. Feasibility and acceptability of the approach were demonstrated; however, the conclusions based on analyses of the post-treatment outcomes were tempered by baseline imbalances across groups.

An observational study of the frequency and pattern of use of epidural steroid injection in 25,479 patients with spinal and radicular pain.

BACKGROUND AND OBJECTIVES: Frequency of epidural steroid injections (ESI) and characteristics of patients receiving them are unknown or poorly described. Patients believed to respond better to ESI include young or middle-aged individuals, those with recent onset or a radicular pattern of pain, and patients without previous spinal surgery. The aim of this study is to estimate the frequency of ESI, to examine the characteristics of patients who have them recommended, and to determine if clinical practice reflects published data pertaining to indications for ESI. METHODS: Descriptive data from 25,479 selected patients with spinal and radicular pain were reviewed. Patients were grouped according to whether or not ESI was recommended, scheduled, prescribed, or continued. Prevalence of ESI use and patient characteristics were compared using standard statistical tests. RESULTS: Overall, ESI were recommended to 2,022 (7.9%) patients. Patients with lumbar pain had ESI proposed 12.6% of the time. Those with cervical and thoracic symptoms had ESI recommended 3.7% and 1.8% of the time, respectively. Patients in whom ESI was recommended were more likely to have pain radiation (P <.001), dermatomal pain distribution (P <.001), and neurologic signs (P <.001). They also had a greater incidence of comorbidities (P <.001) and were older (P <.001). There was no difference in the frequency of prior surgery (P =.169) nor was there a difference based on gender (P =.548) in patients not recommended to have ESI. Patients with symptom duration between 1 month and 1 year were more likely to have ESI recommended. CONCLUSIONS: ESI are commonly used to treat patients with spinal and radicular pain. There is some consistency between clinical practice and published recommendations for ESI use.

Heart-focused anxiety, illness beliefs, and behavioral impairment: comparing healthy heart-anxious patients with cardiac and surgical inpatients.

Psychological features and complaints of persons presenting to medical settings with heart-focused anxiety and noncardiac chest pain are poorly understood. Comparing 20 healthy heart-anxious patients to cardiac and surgical inpatients and nonpatient controls, we found that healthy heart-anxious patients (a) were as afraid of chest pain and heart palpitations as inpatients with heart disease, (b) were as incapacitated by symptoms and using medical services as much as both inpatient groups; and (c) reported higher levels of cardiac disease conviction, heart awareness, and behaviors designed to protect their heart than surgical patients and nonpatients. Compared to all other groups, healthy heart-anxious patients reported more panic and other anxiety disorders, hypochondriacal beliefs, physical symptoms, obsessive-compulsive concerns, and negative affect. Following a hyperventilation test, heart-anxious patients also indicated more distressing symptoms and thoughts, and felt less safe and in control than surgical patients and nonpatients. Results support efforts for a timely recognition, diagnosis, and behavioral treatment of persons with heart-focused anxiety.

Psychometric properties of the Weekly Stress Inventory (WSI): extension to a patient sample with coronary heart disease.

The psychometric characteristics of the Weekly Stress Inventory (WSI) were examined in a sample of medical patients (N = 84) diagnosed with coronary heart disease. In addition to the WSI, patients completed measures assessing recent depressive symptoms, physical symptoms, Type A behavior, and trait anxiety. Patients also monitored stress for 3 weeks (n = 46), completing the Daily Stress Inventory (a measure of minor stress) daily and the WSI at concurrent 1-week intervals. Results indicated that the WSI is an internally consistent and moderately stable measure. Validity of the WSI was supported by (a) strong correlations with a concurrently administered measure of minor stress (concurrent validity); (b) significant positive correlations with measures assessing recent depressive symptoms, physical symptoms, and Type A behavior; and (c) a lack of relationship with a measure of trait anxiety (discriminant validity).

Relationship of learned resourcefulness to measures of pain description, psychopathology and health behavior in a sample of chronic pain patients.

OBJECTIVE: We investigated the association between the coping style of learned resourcefulness and the variables of pain description, pain locus of control, psychological distress, and health-care utilization. DESIGN: A cross-sectional, retrospective, correlational design was used. PATIENTS AND SETTING: The sample was comprised of 87 outpatients from a university-based, multidisciplinary pain clinic. MAIN OUTCOME MEASURES: Self-Control Schedule, pain intensity, McGill Pain Questionnaire, Pain Locus of Control Scale, SCL-90-R, Health-Care Utilization Questionnaire. RESULTS AND CONCLUSIONS: Results indicated that chronic pain patients obtained comparable resourcefulness ratings to normal subjects but there were wide individual differences. Consistent with theoretical predictions, resourcefulness was found to be associated with better psychological adjustment and less impulsive health-care measures. Results suggest that assessment of learned resourcefulness may be useful in predicting behavioral outcome in clinical settings with chronic pain patients.

Relationship of sexual and physical abuse to pain description, coping, psychological distress, and health-care utilization in a chronic pain sample.

OBJECTIVE: We investigated the association of physical/sexual abuse to pain description, coping, psychological distress, and health-care utilization in a heterogeneous sample of chronic pain patients. DESIGN: A cross-sectional, retrospective design was used. Patients were categorized as abused (n = 22) or nonabused (n = 58) based on responses to a valid and reliable sexual/physical abuse questionnaire. MAIN OUTCOME MEASURES: Pain description (Visual Analog Scale measures of pain intensity and frequency, and the McGill Pain Questionnaire); coping ability and attributional style (Functional Interference Estimate, Self-Control Schedule, Pain Locus of Control Scale); psychological distress (SCL-90-R Global Severity Index); and a Health-care utilization measure. RESULTS AND CONCLUSIONS: No differences between abused and nonabused groups were found for the pain description or functional interference variables. Compared to the nonabused group, the abused group had significantly lower Self-Control Schedule scores, higher Pain Locus of Control Scale Chance Factor scores, and higher SCL-90-R Global Severity Index scores and was more likely to use the emergency room for pain symptoms. These results replicate the findings of previous studies of the effects of abuse in more specific pain samples and underscore the importance of assessment of abuse in patients with chronic pain. The data suggest that interventions which involve coping-skills training or self-control management of pain may be affected by an abuse history via reduced perceptions of efficacy, resourcefulness, and beliefs that external variables are responsible for pain.