Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

Effect of ethnicity on care pathway and outcomes in patients hospitalized with influenza A(H1N1)pdm09 in the UK.

Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28-0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08-2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.

Upregulation of GLT-1 by treatment with ceftriaxone alleviates radicular pain by reducing spinal astrocyte activation and neuronal hyperexcitability.

Cervical nerve root injury commonly leads to radicular pain. Normal sensation relies on regulation of extracellular glutamate in the spinal cord by glutamate transporters. The goal of this study was to define the temporal response of spinal glutamate transporters (glial glutamate transporter 1 [GLT-1], glutamate-aspartate transporter [GLAST], and excitatory amino acid carrier 1) following nerve root compressions that do or do not produce sensitivity in the rat and to evaluate the role of glutamate uptake in radicular pain by using ceftriaxone to upregulate GLT-1. Compression was applied to the C7 nerve root. Spinal glutamate transporter expression was evaluated at days 1 and 7. In a separate study, rats underwent a painful root compression and were treated with ceftriaxone or the vehicle saline. Glial glutamate transporter expression, astrocytic activation (glial fibrillary acidic protein [GFAP]), and neuronal excitability were assessed at day 7. Both studies measured behavioral sensitivity for 7 days after injury. Spinal GLT-1 significantly decreased (P < 0.04) and spinal GLAST significantly increased (P = 0.036) at day 7 after a root injury that also produced sensitivity to both mechanical and thermal stimuli. Within 1 day after ceftriaxone treatment (day 2), mechanical allodynia began to decrease; both mechanical allodynia and thermal hyperalgesia were attenuated (P < 0.006) by day 7. Ceftriaxone also reduced (P < 0.024) spinal GFAP and GLAST expression, and neuronal hyperexcitability in the spinal dorsal horn, restoring the proportion of spinal neurons classified as wide dynamic range to that of normal. These findings suggest that nerve root-mediated pain is maintained jointly by spinal astrocytic reactivity and neuronal hyperexcitability and that these spinal modifications are associated with reduced glutamate uptake by GLT-1.

Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischaemic injury.

Biomaterial-guided regeneration represents a novel approach for the treatment of myopathies. Revascularisation and the intramuscular extracellular matrix are important factors in stimulating myogenesis and regenerating muscle damaged by ischaemia. In this study, we used an injectable collagen matrix, enhanced with sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration. The elastic properties of collagen and sLeX-collagen matrices were similar to those of skeletal muscle, and culture of pluripotent mESCs on the matrices promoted their differentiation into myocyte-like cells expressing Pax3, MHC3, myogenin and Myf5. The regenerative properties of matrices were evaluated in ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and IGF binding protein-2 and -5 after 3 days. This was followed by muscle regeneration, including a greater number of regenerating myofibres and increased transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days. Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment of bone marrow-derived progenitor cells, the development of larger arterioles and the restoration of tissue perfusion. Both matrix treatments tended to reduce maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of force and also prevented muscle fatigue. Only sLeX-matrix treatment improved mobility of mice on a treadmill. Together, these results suggest a novel approach for regenerative myogenesis, whereby treatment only with a matrix, which possesses an inherent ability to guide myogenic differentiation of pluripotent stem cells, can enhance the endogenous vascular and myogenic regeneration of skeletal muscle, thus holding promise for future clinical use.

Machine learning and statistical prediction of fastball velocity with biomechanical predictors.

In recent years, one of the most important factors for success among baseball pitchers is fastball velocity. The purpose of this study was to (1) to develop statistical and machine learning models of fastball velocity, (2) to identify the strongest predictors of fastball velocity, and (3) to compare the models' prediction performances. Three dimensional biomechanical analyses were performed on high school (n = 165) and college (n = 62) baseball pitchers. A total of 16 kinetic and kinematic predictors from the entire pitching sequence were included in regression and machine learning models. All models were internally validated through ten-fold cross-validation. Model performance was evaluated through root mean square error (RMSE) and calibration with 95% confidence intervals. Gradient boosting machines demonstrated the best prediction performance [RMSE: 0.34; Calibration: 1.00 (95% CI: 0.999, 1.001)], while regression demonstrated the greatest prediction error [RMSE: 2.49; Calibration: 1.00 (95% CI: 0.85, 1.15)]. Maximum elbow extension velocity (relative influence: 19.3%), maximum humeral rotation velocity (9.6%), maximum lead leg ground reaction force resultant (9.1%), trunk forward flexion at release (7.9%), time difference of maximum pelvis rotation velocity and maximum trunk rotation velocity (7.8%) demonstrated the greatest influence on pitch velocity. Gradient boosting machines demonstrated better calibration and reduced RMSE compared to regression. The influence of lead leg ground reaction force resultant and trunk and arm kinematics on pitch velocity demonstrates the interdependent relationship of the entire kinetic chain during the pitching motion. Coaches, players, and performance professionals should focus on the identified metrics when designing pitch velocity improvement programs.

Intrinsic Dimensionality as a Metric for the Impact of Mission Design Parameters.

High-resolution space-based spectral imaging of the Earth's surface delivers critical information for monitoring changes in the Earth system as well as resource management and utilization. Orbiting spectrometers are built according to multiple design parameters, including ground sampling distance (GSD), spectral resolution, temporal resolution, and signal-to-noise ratio. Different applications drive divergent instrument designs, so optimization for wide-reaching missions is complex. The Surface Biology and Geology component of NASA's Earth System Observatory addresses science questions and meets applications needs across diverse fields, including terrestrial and aquatic ecosystems, natural disasters, and the cryosphere. The algorithms required to generate the geophysical variables from the observed spectral imagery each have their own inherent dependencies and sensitivities, and weighting these objectively is challenging. Here, we introduce intrinsic dimensionality (ID), a measure of information content, as an applications-agnostic, data-driven metric to quantify performance sensitivity to various design parameters. ID is computed through the analysis of the eigenvalues of the image covariance matrix, and can be thought of as the number of significant principal components. This metric is extremely powerful for quantifying the information content in high-dimensional data, such as spectrally resolved radiances and their changes over space and time. We find that the ID decreases for coarser GSD, decreased spectral resolution and range, less frequent acquisitions, and lower signal-to-noise levels. This decrease in information content has implications for all derived products. ID is simple to compute, providing a single quantitative standard to evaluate combinations of design parameters, irrespective of higher-level algorithms, products, applications, or disciplines.

Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave (May-September 2009).

BACKGROUND: During the first wave of pandemic H1N1 influenza in 2009, most cases outside North America occurred in the UK. The clinical characteristics of UK patients hospitalised with pandemic H1N1 infection and risk factors for severe outcome are described. METHODS: A case note-based investigation was performed of patients admitted with confirmed pandemic H1N1 infection. RESULTS: From 27 April to 30 September 2009, 631 cases from 55 hospitals were investigated. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged > or = 65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically-confirmed pneumonia and a raised C-reactive protein (CRP) level (> or = 100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people. CONCLUSIONS: Pandemic H1N1 infection causes disease requiring hospitalisation of previously fit individuals as well as those with underlying conditions. An abnormal chest x-ray or a raised CRP level, especially in patients who are recorded as obese or who have pulmonary conditions other than asthma or COPD, indicate a potentially serious outcome. These findings support the use of pandemic vaccine in pregnant women, children <5 years of age and those with chronic lung disease.

National Beef Market Basket Survey - 2006: External fat thickness measurements and separable component determinations for beef from US retail establishments.

A market basket survey for beef retail cut composition at the retail level (four stores each from two chains in each city) was conducted in 11 US cities from January to March 2006. Beef cuts (n=17,495) were measured for external fat thickness with cuts from the chuck (0.05cm), round (0.05cm), and miscellaneous (0.04cm) having less (P<0.05) fat than cuts from the loin (0.11cm) and rib (0.11cm). Beef cuts (n=1327) were separated physically into separable components with round cuts having more (P<0.05) separable lean (96.63%) than chuck cuts (86.81%) and miscellaneous cuts (86.18%), which had more (P<0.05) separable lean than loin cuts (84.53%) with rib cuts (69.34%) having the lowest (P<0.05) separable lean. Chemical fat from the separable lean differed (P<0.05) between each cut category: round cuts (3.71%), miscellaneous cuts (4.99%), loin cuts (5.60%), chuck cuts (6.90%), and rib cuts (8.61%). Ground beef samples (n=235), with declared lean/fat percentages ranging from 73/27 to 96/4, had overall chemical fat values of 13.41% and moisture values of 67.42%. This survey documents the current beef retail cut and ground beef composition, which is helpful to those who need this information for various dietary and marketing purposes.

Pain characteristics of adults 65 years of age and older referred to a tertiary care pain clinic.

BACKGROUND: Reports indicate that characteristics of older adults with chronic pain may be different than those of younger persons. OBJECTIVE: To study the pain characteristics of older patients presenting to a tertiary pain clinic for the first time. METHODS: Age, sex and relative contributions of biomedical versus psychosocial variables contributing to chronic pain were investigated in patients 65 years of age and older, in comparison with younger patients, from a sample of 1242 consecutive new patients attending a tertiary care pain clinic. The presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision somatoform pain disorders were defined, using an explicated method of ascertaining the biomedical and psychological variables underlying the pain complaints. RESULTS: The older patients (14.7% of the total sample) had relatively more physical problems (concordant with their complaints) but fewer psychological factors contributing to disability than the younger pain patients. Musculoskeletal and neuropathic disorders affected 40.7% and 35.2% of the older patients, respectively, while several patients had more than one painful disorder. Musculoskeletal problems were more prevalent in the women, and neuropathic problems were more prevalent in the men. CONCLUSIONS: The older pain patients are a distinct group. Factors affecting the delayed presentation of older pain patients to the pain clinic and limitations of the present study are discussed.

Dry versus wet aging of beef: Retail cutting yields and consumer palatability evaluations of steaks from US Choice and US Select short loins.

Paired beef short loins from US Choice (n=48) and US Select (n=48) carcasses were assigned to be dry or wet aged for 14, 21, 28 or 35d. After aging, short loins were processed to determine retail yields and processing times. Upon completion of cutting tests, steaks were served to consumers to assess palatability characteristics. Retail cutting tests showed that dry-aged short loins had reduced yields and increased cutting times when compared to wet-aged short loins. Consumers were unable to determine differences between dry- and wet-aged steaks and for aging periods; however, USDA quality grade had a significant impact on consumer perception of palatability attributes.

Identifying muscle and processing combinations suitable for use as beef for fajitas.

Four different treatments-control, papain, blade tenderization, and papain+blade tenderization-were applied to sixty USDA Choice M. diaphragma pars costalis, M. transversus abdominis, M. obliquus abdominis internus, M. rhomboideus, M. trapezius, M. latissimus, and M. serratus ventralis. Trained (n=6) and consumer (n=81) panelists scored papain samples higher for most sensory traits. Treatment tended not to affect the palatability scores of the M. diaphragma pars costalis and M. serratus ventralis, which tended to receive higher scores in comparison to the other muscles. Consumers were willing to purchase the M. latissimus and M. serratus ventralis treated with papain+blade tenderization and papain, respectively, and these muscles performed well enough to be considered as alternatives in the beef fajita market.

Dry versus wet aging of beef: Retail cutting yields and consumer sensory attribute evaluations of steaks from ribeyes, strip loins, and top sirloins from two quality grade groups.

Top Choice (n=48) and Select (n=48) paired bone-in ribeye rolls, bone-in strip loins, and boneless top sirloin butts were assigned randomly to one of two aging treatments, dry or wet, and were aged for 14, 21, 28 or 35d. Cutting tests, performed to determine retail yields and processing times, showed dry-aged subprimals had lower total saleable yield percentages and increased processing times compared to wet-aged subprimals. Sensory and Warner-Bratzler shear evaluation was conducted to determine palatability characteristics. For the most part, aging treatment and aging period did not affect consumer sensory attributes. However, ribeye and top loin steaks from the Top Choice quality grade group received higher sensory ratings than their Select counterparts. For top sirloin steaks, no consumer sensory attributes were affected by aging treatment, aging period, or quality grade group.

Pain characteristics and demographics of patients attending a university-affiliated pain clinic in Toronto, Ontario.

BACKGROUND: Pain clinics tend to see more complex chronic pain patients than primary care settings, but the types of patients seen may differ among practices. OBJECTIVE: The aim of the present observational study was to describe the pain and demographic characteristics of patients attending a university-affiliated tertiary care pain clinic in Toronto, Ontario. METHODS: Data were collected on 1242 consecutive new patients seen over a three-year period at the Comprehensive Pain Program in central Toronto. RESULTS: Musculoskeletal problems affecting large joints and the spine were the predominant cause of pain (more prevalent in women), followed by neuropathic disorders (more prevalent in men) in patients with recognizable physical pathology. The most affected age group was in the 35- to 49-year age range, with a mean pain duration of 7.8 years before the consultation. While 77% of the Comprehensive Pain Program patients had relevant and detectable physical pathology for pain complaints, three-quarters of the overall study population also had significant associated psychological or psychiatric comorbidity. Women, in general, attended the pain clinic in greater numbers and had less apparent physical pathology than men. Finally, less than one in five patients was employed at the time of referral. CONCLUSIONS: The relevance of the data in relation to other pain clinics is discussed, as well as waiting lists and other barriers faced by chronic pain patients, pain practitioners and pain facilities in Ontario and Canada.

Ethnocultural and sex characteristics of patients attending a tertiary care pain clinic in Toronto, Ontario.

BACKGROUND: Ethnocultural factors and sex may greatly affect pain perception and expression. Emerging literature is also documenting racial and ethnic differences in pain access and care. OBJECTIVE: To define the sex and ethnocultural characteristics of patients attending a tertiary care, university-affiliated pain clinic in Toronto, Ontario. METHODS: Data were collected on 1242 consecutive, new patients seen over a three-year period at the Comprehensive Pain Program (CPP) in downtown Toronto. Data were compared with the Canada 2001 Census. RESULTS: English-speaking, Canadian-born patients constituted 58.6% of the CPP population, similar to the 2001 Canadian Census data for the Greater Toronto Area. Certain visible minority groups (Indo-Pakistani and Chinese) were significantly under-represented, while European groups were over-represented. While women outnumbered men, they presented with lower levels of physical pathology in general, particularly in certain ethnic groups. Patients from Europe (representing primarily immigrants who arrived in Canada before 1960), were older, by 10 years to 15 years, than the average CPP population, and had a much higher incidence of physical or medical disorders. CONCLUSIONS: The implications of the study and the importance of sex and ethnicity in terms of presentation to Canadian pain clinics are discussed. Future well-designed studies are needed to shed light on the role of both patients' and physicians' ethnicity and sex in pain perception and expression, decision-making regarding pain treatments and acceptance of pain treatments.

Mathematical modeling of the effects of CK2.3 on mineralization in osteoporotic bone.

Osteoporosis is caused by decreased bone mineral density (BMD) and new treatments for this disease are desperately needed. Bone morphogenetic protein 2 (BMP2) is crucial for bone formation. The mimetic peptide CK2.3 acts downstream of BMP2 and increases BMD when injected systemically into the tail vein of mice. However, the most effective dosage needed to induce BMD in humans is unknown. We developed a mathematical model for CK2.3-dependent bone mineralization. We used a physiologically based pharmacokinetic (PBPK) model to derive the CK2.3 concentration needed to increase BMD. Based on our results, the ideal dose of CK2.3 for a healthy individual to achieve the maximum increase of mineralization was about 409 µM injected in 500 µL volume, while dosage for osteoporosis patients was about 990 µM. This model showed that CK2.3 could increase the average area of bone mineralization in patients and in healthy adults.

Influence of drug exposure parameters on the activity of paclitaxel in multicellular spheroids.

Paclitaxel is a chemotherapeutic drug which has clinical activity against several solid tumours including ovarian and metastatic breast cancers. Despite extensive preclinical evaluation in several experimental models, no studies have determined the effect of taxol on multicellular spheroids, a model which closely mimics the microregions of solid tumours. MCF-7 human breast carcinoma spheroids were significantly less sensitive than monolayers with IC50 values of 14.33 +/- 4.51 microM and 0.15 +/- 0.09 microM, respectively, following a 1 h drug exposure. Similarly, DLD-1 human colon carcinoma spheroids were also more resistant (IC50 = 33.0 +/- 8.89 microM) than monolayers (IC50 = 0.36 +/- 0.14 microM) following a 1 h drug exposure. Paclitaxel was unable to penetrate DLD-1 multicell layers (22 microns in thickness), suggesting that suboptimal drug exposures to paclitaxel occur in cells which reside some distance away from the surface of the spheroid. In the case of DLD-1 spheroids, extending the exposure time to 24 h whilst maintaining the same overall concentration x time (C x T) drug exposure parameters, resulted in greater cell kill (C x T required to kill 50% of cells = 13.67 +/- 3.21 microM/h) compared with 1 h drug exposures (C x T required to kill 50% of cells = 33.00 +/- 8.89 microM/h). Similar results were obtained with MCF-7 spheroids. In monolayers cultures, dose-response curves contained a marked plateau phase (a characteristic feature of cell cycle phase specific drug) and in the case of MCF-7 cells, cell kill was proportional to T as opposed to C x T. These results support the use of prolonged infusions of paclitaxel in the clinic, as extending the duration of drug exposure not only allows more cells to enter sensitive phases of the cell cycle, but would also allow paclitaxel more time to penetrate into avascular regions of solid tumours. It is likely that paclitaxel will only be effective against cells which reside close to tumour blood vessels and combination therapy with bioreductive drugs (such as tirapazamine) may produce synergistic effects in vivo.

In vitro and in vivo activity of LS 4477 and LS 4559, novel analogues of the tubulin binder estramustine.

LS 4477 and LS 4559, two of a series of N-acyl-aminoalkyl phenyl ethers, are rationally designed compounds based on the tubulin binder estramustine. This study investigated their mechanism of action and compared their effectiveness in relation to estramustine in vitro against a panel of human and murine cell lines and in vivo against two murine colon tumour models (MAC). At biologically relevant concentrations, LS 4477 and LS 4559 caused a 59.9 and 56% reduction in tubulin assembly, respectively, compared with a 28.4% reduction in tubulin assembly by estramustine. The analogues were approximately 100 times more potent in chemosensitivity tests in vitro than the parent compound. Both analogues were orally active against the MAC 15A murine tumour model, to a greater extent than estramustine, producing significant growth delays (P<0.01). Significant activity was also shown against the slower growing MAC 26 tumour for LS 4577 (the soluble pro-drug of LS 4559). The results presented in this study suggest these compounds warrant further development with a view to assessing their clinical activity.

Diagnosis of respiratory virus infections using GACELISA of urinary antibodies.

Sensitive and specific methods are needed to diagnose respiratory virus infections using body fluids such as urine that, unlike blood samples, are readily obtained by non-invasive means. Immunoglobulin G antibody capture enzyme-linked immunosorbent assays were developed for detection of antibody rises to respiratory syncytial virus and influenza A/Taiwan (H1N1) after initial quantification and adjustment of urinary IgG concentration. Of 24 elderly subjects whose sera were assayed by the complement fixation test for antibody to RSV, seven had convalescent titres > or = 32, and five had > or = 4-fold rises in titre. Acute and convalescent urines for six of these seven subjects were tested for virus-specific urinary IgG by GACELISA. Four of four persons with > or = 4-fold rises in CFT had urine ELISA convalescent to acute ratios of > or = 1.8 whereas two subjects with convalescent CF titres > 16, but no increase in serum antibody titre, had urine convalescent/acute ratios of 1.0. Ten subjects with > or = 4-fold rises in CFT or HI antibodies to influenza A/Taiwan had urine ELISA ratios of > or = 1.4 when samples taken on the day of influenza vaccination and 16 days later were compared. These preliminary observations demonstrate clinically significant rises in respiratory pathogen antibody levels between acute and convalescent urine samples, provided that total urinary IgG concentrations are quantified and then standardised.