Revealing latent pole and zone line information in atom probe detector maps using crystallographically correlated metrics.

Poles and zone lines observed within atom probe field evaporation images are useful for a range of atom probe crystallography studies, including calibration of the reconstruction and crystallographic characterisation of microstructural features such as grain boundaries. However, this information is not always readily apparent. Techniques for plotting crystallographically correlated metrics contained within atom probe data to enhance pole and zone line contrast across the detector space are developed. This includes consideration of the electric field, molecular ions, lattice structure retained within the reconstruction, specific elemental species, the number of pulses between detection events, and the lateral distance between sequential detection events. These approaches are then applied to experimental atom probe tomography datasets on technically pure Al, nanocrystalline Al, highly doped Si, and additively manufactured Inconel 738, Haynes 282, and Ti-6Al-4V. The results facilitate the extension of atom probe crystallography studies to a broader range of crystalline datasets where crystallographic information is not readily apparent from existing methods, as well as a deeper understanding of field evaporation behaviour during an atom probe experiment.

Correlative study of lattice imperfections in long-range ordered, nano-scale domains in a Fe-Co-Mo alloy.

Recent advancements in data mining methods in atom probe microscopy have enabled new quantitative chemical and microstructural characterization beyond the standard three-dimensional reconstruction. For example, spatial distribution maps have been developed to enable visualisation of the local lattice occupation of a selected region of interest. However, the precision of such studies yet remains unknown as correlation with complementary methods would be required. Therefore, a correlative study of atom probe microscopy, neutron diffraction and microstructural modelling of long-range ordered, nano-scale domains in a well-researched Fe-Co-Mo Maraging-type steel is presented here. Its microstructure consists of Mo-enriched µ-phase (Fe,Co)7Mo6 particles embedded into a body-centred cubic FeCo matrix. Previous research has shown that under slow cooling conditions, this matrix partially decomposes into nano-scale B2 long-range ordered domains surrounded by disordered regions, resulting in reduced toughness in potential cutting applications. Usually, a long-range order parameter S referring to ideal B2 long-range order is assumed within such domains according to neutron diffraction. However, atom probe microscopy and modelling results presented in the current study indicate lattice imperfections with a partial substitution of atoms on the Fe- and Co-sublattices. After considering preferential retention effects during the atom probe experiment, a model unit cell is presented to define the observed imperfect B2 long-range order as pseudo-D03 long-range order, and the potential impact on the materials properties is discussed.

Phase nucleation through confined spinodal fluctuations at crystal defects evidenced in Fe-Mn alloys.

Analysis and design of materials and fluids requires understanding of the fundamental relationships between structure, composition, and properties. Dislocations and grain boundaries influence microstructure evolution through the enhancement of diffusion and by facilitating heterogeneous nucleation, where atoms must overcome a potential barrier to enable the early stage of formation of a phase. Adsorption and spinodal decomposition are known precursor states to nucleation and phase transition; however, nucleation remains the less well-understood step in the complete thermodynamic sequence that shapes a microstructure. Here, we report near-atomic-scale observations of a phase transition mechanism that consists in solute adsorption to crystalline defects followed by linear and planar spinodal fluctuations in an Fe-Mn model alloy. These fluctuations provide a pathway for austenite nucleation due to the higher driving force for phase transition in the solute-rich regions. Our observations are supported by thermodynamic calculations, which predict the possibility of spinodal decomposition due to magnetic ordering.

How Insightful Is 'Insight'? New Caledonian Crows Do Not Attend to Object Weight during Spontaneous Stone Dropping.

It is highly difficult to pinpoint what is going through an animal's mind when it appears to solve a problem by 'insight'. Here, we searched for an information processing error during the emergence of seemingly insightful stone dropping in New Caledonian crows. We presented these birds with the platform apparatus, where a heavy object needs to be dropped down a tube and onto a platform in order to trigger the release of food. Our results show New Caledonian crows exhibit a weight inattention error: they do not attend to the weight of an object when innovating stone dropping. This suggests that these crows do not use an understanding of force when solving the platform task in a seemingly insightful manner. Our findings showcase the power of the signature-testing approach, where experiments search for information processing biases, errors and limits, in order to make strong inferences about the functioning of animal minds.

Effect of Ovariohysterectomy at the Time of Tumor Removal in Dogs with Mammary Carcinomas: A Randomized Controlled Trial.

BACKGROUND: Ovarian hormones play crucial roles in mammary carcinogenesis. However, whether ovarian ablation by ovariohysterectomy (OHE) improves the prognosis in dogs with mammary carcinomas is unclear. OBJECTIVES: Determine if OHE at the time of mastectomy improves the prognosis in dogs with mammary carcinomas and evaluate if hormonal factors influence the effect of OHE. ANIMALS: Sixty intact dogs with mammary carcinomas. METHODS: Dogs were randomly assigned in a 1:1 ratio to undergo OHE (n = 31) or not (n = 29) at the time of tumor removal. Peri-surgical serum estradiol (E2) and progesterone concentrations were measured, tumor diagnosis was confirmed histologically, and tumor estrogen and progesterone receptor status was immunohistochemically determined. The dogs were monitored for recurrence and metastases every 3-4 months for at least 2 years. Uni- and multivariable survival analyses were performed with relapse and all-cause death as endpoints in addition to univariable subgroup analyses. RESULTS: Overall, OHE did not significantly decrease hazard of relapse (hazard ratio [HR], 0.64; P = .18) or all-cause death (HR, 0.87; P = .64) in univariable analyses. In multivariable analysis OHE did not significantly influence the hazard of relapse (HR, 0.54; P = .12), but an interaction effect was identified between ER status and E2 (P = .037). Subgroup analysis identified decreased hazard of relapse in the OHE group compared to the non-OHE group in the subsets of dogs with increased E2 (HR, 0.22; P = .012) or grade 2 tumors (HR, 0.26; P = .02). CONCLUSION: Dogs with grade 2, ER-positive tumors, or with increased peri-surgical serum E2 concentration represent a subset of dogs with mammary carcinomas likely to benefit from OHE.

Quantitative chemical-structure evaluation using atom probe tomography: Short-range order analysis of Fe-Al.

Short-range-order (SRO) has been quantitatively evaluated in an Fe-18Al (at%) alloy using atom probe tomography (APT) data and by calculation of the generalised multicomponent short-range order (GM-SRO) parameters, which have been determined by shell-based analysis of the three-dimensional atomic positions. The accuracy of this method with respect to limited detector efficiency and spatial resolution is tested against simulated D03 ordered data. Whilst there is minimal adverse effect from limited atom probe instrument detector efficiency, the combination of this with imperfect spatial resolution has the effect of making the data appear more randomised. The value of lattice rectification of the experimental APT data prior to GM-SRO analysis is demonstrated through improved information sensitivity.

Moving back: The radiation dose received from lumbar spine quantitative fluoroscopy compared to lumbar spine radiographs with suggestions for dose reduction.

PURPOSE: Quantitative fluoroscopy is an emerging technology for assessing continuous inter-vertebral motion in the lumbar spine, but information on radiation dose is not yet available. The purposes of this study were to compare the radiation dose from quantitative fluoroscopy of the lumbar spine with lumbar spine radiographs, and identify opportunities for dose reduction in quantitative fluoroscopy. METHODS: Internationally reported dose area product (DAP) and effective dose data for lumbar spine radiographs were compared with the same for quantitative fluoroscopy and with data from a local hospital for functional radiographs (weight bearing AP, lateral, and/or flexion and extension) (n = 27). The effects of procedure time, age, weight, height and body mass index on the fluoroscopy dose were determined by multiple linear regression using SPSS v19 software (IBM Corp., Armonck, NY, USA). RESULTS AND CONCLUSION: The effective dose (and therefore the estimated risk) for quantitative fluoroscopy is 0.561 mSv which is lower than in most published data for lumbar spine radiography. The dose area product (DAP) for sagittal (flexion + extension) quantitative fluoroscopy is 3.94 Gy cm2 which is lower than local data for two view (flexion and extension) functional radiographs (4.25 Gy cm2), and combined coronal and sagittal dose from quantitative fluoroscopy (6.13 Gy cm2) is lower than for four view functional radiography (7.34 Gy cm2). Conversely DAP for coronal and sagittal quantitative fluoroscopy combined (6.13 Gy cm2) is higher than that published for both lumbar AP or lateral radiographs, with the exception of Nordic countries combined data. Weight, procedure time and age were independently positively associated with total dose, and height (after adjusting for weight) was negatively associated, thus as height increased, the DAP decreased.

Effect of ovariohysterectomy at the time of tumor removal in dogs with benign mammary tumors and hyperplastic lesions: a randomized controlled clinical trial.

BACKGROUND: Nonmalignant mammary tumors (NMT) are common in intact female dogs. Little is known about the clinical significance of these tumors, and the effect of ovariohysterectomy (OHE) on their development. HYPOTHESIS: Ovarian hormone ablation through OHE decreases the risk of new tumors and thereby improves long-term prognosis for dogs with NMT. ANIMALS: Eighty-four sexually intact bitches with NMT. METHODS: Dogs were allocated to undergo OHE (n = 42) or not (n = 42) at the time of NMT removal in a randomized clinical trial. Tumor diagnosis was confirmed histologically in all subjects. Information about new tumor development was collected via follow-up phone calls and recheck examinations. Separate survival analyses were performed with the endpoints new tumor development and death. Cause of death was classified as related or unrelated to mammary tumor. In addition to OHE status, the influence of age, body weight, breed, tumor size, tumor number, tumor duration, type of surgery, and tumor histology was investigated. RESULTS: New mammary tumor(s) developed in 27 of 42 (64%) intact dogs and 15 of 42 (36%) ovariohysterectomized dogs (hazard ratio 0.47, P = .022). Nine of the 42 dogs (21%) which developed new tumors were euthanized because of mammary tumor. Survival was not significantly different between the 2 treatment groups. In the intact group, nine dogs subsequently developed ovarian-uterine diseases. CONCLUSION: Ovariohysterectomy performed at the time of mammary tumor excision reduced the risk of new tumors by about 50% among dogs with NMT. Survival was not significantly affected. Adjuvant OHE should be considered in adult dogs with mammary tumors.

Will shared decision making between patients with chronic musculoskeletal pain and physiotherapists, osteopaths and chiropractors improve patient care?

BACKGROUND: Chronic musculoskeletal pain (CMP) is treated in primary care by a wide range of health professionals including chiropractors, osteopaths and physiotherapists. AIMS: To explore patients and chiropractors, osteopaths and physiotherapists' beliefs about CMP and its treatment and how these beliefs influenced care seeking and ultimately the process of care. METHODS: Depth interviews with a purposive sample of 13 CMP patients and 19 primary care health professionals (5 osteopaths, 4 chiropractors and 10 physiotherapists). RESULTS: Patients' models of their CMP evolved throughout the course of their condition. Health professionals' models also evolved throughout the course of their treatment of patients. A key influence on patients' consulting behaviour appeared to be finding someone who would legitimate their suffering and their condition. Health professionals also recognized patients' need for legitimation but often found that attempts to explore psychological factors, which may be influencing their pain could be construed by patients as delegitimizing. Patients developed and tailored their consultation strategies throughout their illness career but not always in a strategic fashion. Health professionals also reflected on how patients' developing knowledge and changing beliefs altered their expectations. Therefore, overall within our analysis, we identified three themes: 'the evolving nature of patients and health professionals models of understanding CMP'; 'legitimating suffering' and 'development and tailoring of consultation and treatment strategies throughout patients' illness careers'. CONCLUSIONS: Seeking care for any condition is not static but a process particularly for long-term conditions such as CMP. This may need to be taken into account by both CMP patients and their treating health professionals, in that both should not assume that their views about causation and treatment are static and that instead they should be revisited on a regular basis. Adopting a shared decision-making approach to treatment may be useful particularly for long-term conditions; however, in some cases, this may be easier said than done due to both patients' and health professionals' sometimes discomfort with adopting such an approach. Training and support for both health professionals and patients may be helpful in facilitating a shared decision-making approach.

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence.

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty-six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.

Irrigation and fertilization effects on seed number, size, germination and seedling growth: implications for desert shrub establishment.

Plants with limited resources adjust partitioning among growth, survival, and reproduction. We tested the effects of water and nutrient amendments on seed production, size, and quality in Sarcobatus vermiculatus (greasewood) to assess the magnitude and importance of changes in reproductive partitioning. In addition, we assessed interactions among the environment of seed-producing plants (adult plant scale), seed size, and seedling microenvironment (seedling scale) on successful seedling establishment. Interactions of these factors determine the scale of resource heterogeneity that affects seedling establishment in deserts. Both total number of seeds produced per plant and seed quality (weight and germination) increased significantly in the enriched treatment in a 3-year field experiment. Seedling length 3 days after germination and seed N concentration, other measures of seed quality, were higher for seed from both irrigated and enriched plants than for seed from control plants. Field S. vermiculatus seed production and quality can be substantially increased with irrigation and nutrient enrichment at the adult plant scale and this allows management of seed availability for restoration. However, based on a greenhouse study, seedling environment, not the environment of the seed-producing plant or seed size, was the most important factor affecting seedling germination, survival, and growth. Thus it appears that production of more seed may be more important than improved seed quality, because higher quality seed did not compensate for a low-resource seedling environment. For both natural establishment and restoration this suggests that heterogeneity at the scale of seedling microsites, perhaps combined with fertilization of adult shrubs (or multi-plant patches), would produce the greatest benefit for establishing seedlings in the field.

Prevalence and comparative troublesomeness by age of musculoskeletal pain in different body locations.

BACKGROUND: Chronic pain has large health care costs and a major impact on the health of those affected. Few studies have also considered the severity of pain in different parts of the body across all age groups. OBJECTIVES: To measure the prevalence and troublesomeness of musculoskeletal pain in different body locations and age groups, in a consistent manner, without using location specific health outcome measures. METHODS: A cross-sectional postal survey of 4049 adults registered with 16 MRC General Practice Research Framework practices. Frequency of chronic pain overall and troublesome pain by location and age was calculated. Logistic regression was undertaken to explore the relationship between chronic pain and demographic factors. RESULTS: We received 2504 replies; response rate 60%. The prevalence of chronic pain was 41%. The prevalence of chronic pain rose from 23% in 18-24 year olds reaching a peak of 50% in 55-64 year olds. Troublesome pain over the last 4 weeks was commonest in the lower back (25%), neck (18%), knee (17%) and shoulder (17%). Troublesome wrist, elbow, shoulder, neck and lower back pain were most prevalent in the 45- to 64-year-age groups. Troublesome hip/thigh, knee and ankle/foot pain were most prevalent in those aged 75 or more. CONCLUSIONS: Great efforts have been made to develop and test treatments for low back pain. Our findings suggest that the overall prevalence of troublesome neck, knee and shoulder pain approaches that of troublesome low back pain and that similar efforts may be required to improve the management these pains.

Chronic musculoskeletal pain rarely presents in a single body site: results from a UK population study.

OBJECTIVE: To investigate the frequency and health impact of chronic multi-site musculoskeletal pain, in a representative UK sample. METHOD: Population postal questionnaire survey, using 16 general practices in the southeast of England, nationally representative urban/rural, ethnic and socioeconomic mix. A random selection of 4049 registered patients, aged 18 or over, were sent a questionnaire. The main outcome measures were chronic pain location, identified using a pain drawing; distress, pain intensity and disability as measured by the GHQ12 and the Chronic Pain Grade. RESULTS: A total of 2445 patients (60%) responded to the survey (44% male, mean age 52 yrs); 45% had chronic musculoskeletal pain. Of those with chronic pain, three quarters had pain in multiple sites (two or more sites). Variables significantly predicting this were: age under 55, [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4, 0.6]; psychological distress (OR 1.8, CI at 95% 1.4, 2.2) and high pain intensity (OR 5.2, CI at 95% 4.1, 6.7). Only 33% of multi-site pain distributions conformed to the American College of Rheumatology definition of chronic widespread pain. CONCLUSIONS: Multi-site chronic pain is more common than single-site chronic pain and is commonly associated with other problems. Indiscriminate targeting of research and care for chronic musculoskeletal pain on single sites may often be inappropriate.

Are all aciclovir cream formulations bioequivalent?

Topical aciclovir cream (ACV, Zovirax Cream) containing 40% propylene glycol (PG), the optimum found for skin penetration, is clinically effective in the treatment of recurrent herpes labialis. One hundred and thirty-nine ACV generic creams were analysed and 80% of these contained less than 20% PG. From this, we hypothesised that these generics might be bioinequivalent to the innovator cream. A pilot in vitro skin permeation study compared the innovator cream with two generics containing about 15% PG. Next, 10 generics containing 0-15% PG were tested in an independent laboratory. Finally, a PG dose-ranging study was conducted in Zovirax cream base. In all studies, human skin was used and ACV analysed by LC-MS-MS. In the pilot study, the innovator cream delivered 7.5-fold more ACV than the two generics. Superiority was confirmed in the second study against all 10 ACV generic creams. By grouping the creams according to PG content, a relationship to ACV skin permeation was suggested. The PG dose effect was confirmed in the third study. These studies suggest that not all marketed ACV creams are bioequivalent to the clinically proven innovator. Given the magnitude of the differences seen, there is concern over therapeutic inequivalence of generic ACV creams to the innovator cream.

Spinal manipulation for low-back pain: a treatment package agreed to by the UK chiropractic, osteopathy and physiotherapy professional associations.

Trials of manipulative treatment have been compromised by, amongst other things, different definitions of the therapeutic procedures involved. This paper describes a spinal manipulation package agreed by the UK professional bodies that represent chiropractors, osteopaths and physiotherapists. It was devised for use in the UK Back pain Exercise And Manipulation (UK BEAM) trial--a national study of physical treatments in primary care funded by the Medical Research Council and the National Health Service Research and Development Programme. Although systematic reviews have reported some beneficial effects of spinal manipulation for low-back pain, due to the limited methodological quality of primary studies and difficulties in defining manipulation, important questions have remained unanswered. The UK BEAM trial was designed to answer some of those questions. Early in the design of the trial, it was acknowledged that the spinal manipulation treatment regimes provided by practitioners from the three professions shared more similarities than differences. Because the trial design specifically precluded comparison of the effect between the professions, it was necessary to devise a homogenous package representative of, and acceptable to, all three. The resulting package is 'pragmatic', in that it represents what happens to most people undergoing manipulation, and 'explanatory' in that it excludes discipline-specific variations and other ancillary treatments.

Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.

The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.

Communication between general practitioners and chiropractors.

OBJECTIVE: Good communication between health care professionals has proved to be important in ensuring high standards of care. Patients have shown an increased use of complementary medicine (eg, chiropractic) in addition to conventional medicine. However, this does not automatically guarantee good cooperation and communication between complementary practitioners and conventional practitioners. The objective of this study was to assess the nature and quality of communication between general practitioners and chiropractors (in The Netherlands) and to look for areas for improvement. DESIGN AND SETTING: Postal questionnaires were sent to general practitioners requesting personal and practice details and asking about their knowledge of chiropractic, present communications, opinions on chiropractic terminology, and preferences with regard to communications with patients. SUBJECTS: A total of 252 general practitioners in 84 Dutch cities. RESULTS: A total of 115 questionnaires (46%) were returned. Almost all of the general practitioners had at least heard of chiropractic. Most information came from patients who were treated by chiropractors (78%). Only 10% of the general practitioners refer their patients to a chiropractor on a regular basis. Referral of patients was found to be significantly related to the general practitioners' perceived knowledge of chiropractic and positive opinions regarding their past communications with chiropractors. More than 80% of the general practitioners said that they were interested in receiving (or continuing to receive) feedback reports, even if they did not personally refer the patient to the chiropractor. Chiropractic feedback reports often seem to contain confusing terminology (40%), which might negatively influence communication (66%). General practitioners preferred a typed (88%), short (69%) feedback report, preferably sent after the last treatment (72%). CONCLUSIONS: The results of this study show most general practitioners to have a neutral to positive attitude toward communication with chiropractors. The general practitioners' preferences with regard to the technical aspects of a feedback report concur with the results of similar surveys in the field and can be used as guidelines for written communications. Factors that negatively influence communication between general practitioners and chiropractors seem to be confusing terminology, a limited knowledge of chiropractic, and bad experiences in previous communications. Recognition and illumination of these factors is a prerequisite to the development of good communication.

Adverse effects of spinal manipulation.

Guidelines on acute back pain recommend spinal manipulation, but some commentators express concern that the adverse effects are under-reported. Eleven chiropractors distributed questionnaires to 108 consecutive new patients aged > 18 years, enquiring about adverse effects one hour, one day and two days after spinal manipulation. The forms were to be completed anonymously. 80 questionnaires (74%) were returned, 68 suitable for analysis. 28 patients reported adverse effects at one hour after treatment, the most common of which were extra pain (14) and radiating pain (9). 8 had reactions beginning the morning after. No serious adverse effects were reported. The adverse reactions, recorded in 53% of respondents, are those to be expected from a treatment that entails initial discomfort. They need to be set against the long-term benefits of spinal manipulation.