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Background: The Universal Health Coverage goals call for access to affordable palliative care to reduce inequities in "total pain" and suffering. To achieve this, a patient-centred understanding of these inequities is required.Aim: To assess association of total pain and suffering (i.e. physical, psychological, social, and spiritual health outcomes) and perceived health care quality with financial difficulties among stage IV solid malignancy patients.Design: Using baseline data from the COMPASS cohort study, we assessed total pain and suffering including physical (physical and functional well-being, pain, symptom burden), psychological (anxiety, depression, emotional well-being), social (social well-being), and spiritual (spiritual well-being, hope) outcomes and perceived health care quality (physician communication, nursing care, and coordination/responsiveness). Financial difficulties were scored by assessing patient perception of the extent to which their resources were meeting expenses for their treatments, daily living, and other obligations. We used multivariable linear/logistic regression to test association between financial difficulties and each patient-reported outcome.Setting/participants: Six hundred stage IV solid malignancy patients in Singapore.Results: Thirty-five percent reported difficulty in meeting expenses. A higher financial difficulties score was associated with worse physical, psychological, social, spiritual outcomes, and lower perceived quality of health care coordination and responsiveness (i.e. greater total pain and suffering) (all p < 0.05). These associations persisted after adjustment for socio-economic indicators.Conclusion: Results identify advanced cancer patients with financial difficulties to be a vulnerable group with greater reported total pain and suffering. A holistic patient-centred approach to care at end-of-life may help meet goals for Universal Health Coverage. [ABSTRACT FROM AUTHOR]

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P<10−77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43-0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04-4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS. [ABSTRACT FROM AUTHOR]

Background In cases of locally advanced breast cancer (LABC), preoperative ("neoadjuvant") therapy was traditionally reserved to render the patient operable. More recently, neoadjuvant therapy, particularly chemotherapy, is being used in patients with operable disease to increase the opportunity for breast conservation. Despite the increasing use of preoperative chemotherapy, rates of pathologic complete response, a surrogate marker for disease-free survival, remain modest in patients with locally advanced disease and particularly so when the tumour is estrogen or progesterone receptor-positive and HER2-negative. A new paradigm for LABC patients is needed. In other solid tumours (for example, rectal, esophageal, and lung cancers), concurrent chemoradiotherapy (CCRT) is routinely used in neoadjuvant and adjuvant treatment protocols alike. Results The literature suggests that CCRT in LABC patients with inoperable disease is associated with response rates higher than would be anticipated with systemic therapy alone. Conclusions Ongoing trials in this field are eagerly awaited to determine if CCRT should become the new paradigm. [ABSTRACT FROM AUTHOR]

The aim of this study is to estimate the frequency of pathologic complete response (pCR) after neoadjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation. One hundred and seven women with breast cancer and a BRCA1 mutation, who were diagnosed with stage I to III breast cancer between December 2006 and June 2014, were treated with cisplatin 75 mg/m every 3 weeks for four cycles, followed by mastectomy and conventional chemotherapy. Information was collected on clinical stage, grade, hormone receptor status, and Her2neu status prior to treatment. pCR was determined by review of surgical specimens. One hundred and seven patients were enrolled in the study, including 93 patients who were treated for first primary breast cancer and 14 patients who had previously received treatment for a prior cancer. A pCR was observed in 65 of the 107 patients (61 %). Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including HER 2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC. [ABSTRACT FROM AUTHOR]

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11-12, 2010. The meeting focused on current and future directions in LABC treatment and research, the specific benefits of LABC as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in LABC research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference. [ABSTRACT FROM AUTHOR]

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11-12, 2010. The meeting focused on current and future directions in LABC treatment and research, the specific benefits of LABC as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in LABC research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference. [ABSTRACT FROM AUTHOR]

AMP-activated protein kinase (AMPK) has a broad role in the regulation of glucose and lipid metabolism making it a promising target in the treatment of type 2 diabetes mellitus. We therefore sought to characterise for the first time the effects of chronic AMPK activation on skeletal muscle carbohydrate metabolism in carriers of the rare gain-of-function mutation of the gene encoding AMPKγ3 subunit, PRKAG3 R225W. Aspects of fuel metabolism were studied in vitro in myocytes isolated from vastus lateralis of PRKAG3 R225W carriers and matched control participants. In vivo, muscular strength and fatigue were evaluated by isokinetic dynamometer and surface electromyography, respectively. Glucose uptake in exercising quadriceps was determined using [18F]fluorodeoxyglucose and positron emission tomography . Myotubes from PRKAG3 R225W carriers had threefold higher mitochondrial content ( p < 0.01) and oxidative capacity, higher leak-dependent respiration (1.6-fold, p < 0.05), higher basal glucose uptake (twofold, p < 0.01) and higher glycogen synthesis rates (twofold, p < 0.05) than control myotubes. They also had higher levels of intracellular glycogen ( p < 0.01) and a trend for lower intramuscular triacylglycerol stores. R225W carriers showed remarkable resistance to muscular fatigue and a trend for increased glucose uptake in exercising muscle in vivo. Through the enhancement of skeletal muscle glucose uptake and increased mitochondrial content, the R225W mutation may significantly enhance exercise performance. These findings are also consistent with the hypothesis that the γ3 subunit of AMPK is a promising tissue-specific target for the treatment of type 2 diabetes mellitus, a condition in which glucose uptake and mitochondrial function are impaired. [ABSTRACT FROM AUTHOR]

Obesity is an important risk factor for the development of type 2 diabetes, but not all obese individuals develop this complication. The clinical signs of type 2 diabetes can often be reversed with weight loss; however, it is unknown whether the skeletal muscle oxidative stress associated with type 2 diabetes remains after weight loss. We hypothesised that chronic exposure to high glucose and insulin would re-elicit impaired metabolism in primary myotubes from patients with a history of type 2 diabetes. Obese participants with or without type 2 diabetes completed a standardised weight loss protocol, following which all participants were euglycaemic and had similar indices of insulin sensitivity. Satellite cells were isolated from muscle biopsies and differentiated under low or high glucose and insulin conditions (HGI). Cells from participants with no history of type 2 diabetes showed robust increases in mitochondrial content, citrate synthase and cytochrome c oxidase activities when exposed to HGI. This increase in oxidative capacity was absent in cells from patients with a history of type 2 diabetes. High glucose and insulin caused increased oxidative damage in cells from the latter, despite higher superoxide dismutase expression. Cells from patients with a history of type 2 diabetes were unable to decrease mitochondrial membrane potential in response to HGI, potentially due to lower levels of uncoupling protein-3. This is the first report to note that primary myotubes from patients with a history of type 2 diabetes are unable to adapt to a hyperglycaemic–hyperinsulinaemic challenge. We have demonstrated that impaired mitochondrial biogenesis and an inability to manage oxidative stress define a muscle phenotype at risk of obesity-associated type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Ten patients with breast cancer and a breast cancer susceptibility gene 1 (BRCA1) mutation, who presented with stages I to III breast cancer between December 2006 and 2007, were treated with four cycles of neoadjuvant cisplatin, followed by mastectomy and conventional chemotherapy. Methods The excised breast tissue and lymph nodes were examined for the presence of residual disease. Results Pathologic complete response was observed in nine patients (90%). Conclusions Platinum-based chemotherapy appears to be effective in a high proportion of patients with BRCA1-associated breast cancers. Clinical trials are now warranted to determine the optimum treatment for this subgroup of breast cancer patients. [ABSTRACT FROM AUTHOR]

This paper reports the application of image analysis methods we developed previ ously to characterize fiber diameter distribution in nonwovens using a "distance trans form." The method is verified by a series of simulated nonwoven images as well as some real web images used previously, including a carded web, a relatively dense spunbonded fabric, and another relatively open area-bonded spunbonded. The results indicate that the distance transform can be used successfully to characterize fiber diameter. [ABSTRACT FROM PUBLISHER]

, This paper addresses the development of an image analysis technique for direct tracking of fibers in an assembly. The algorithms are evaluated using simulated images presented in an earlier part of the series. The tracking method appears to be extremely efficient in determining fiber orientation distribution in nonwovens regardless of their structural characteristics. [ABSTRACT FROM PUBLISHER]

In nonwovens, fiber orientation is an important characteristic because it directly influences the properties of the material. In a series of papers, we plan to explore the viability of image analysis algorithms for characterizing fiber orientation. In the first part of this series, we present a simulation scheme to produce images to test these different algorithms. As part of the series, we will present a direct tracking method in Part II, as well as Fourier and flow field analyses in subsequent parts for characterizing fiber orientation. [ABSTRACT FROM PUBLISHER]

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids. [ABSTRACT FROM PUBLISHER]

In vitro monocyte maturation was studied in patients with squamous cell carcinoma of the lung--limited to the ipsilateral hemithorax in 30 and more extensive in 40. The patients were studied prospectively and initial monocyte maturation was correlated with survival. Monocyte maturation in patients with limited disease before treatment ranged from 3.1 to 57.6% with a median value of 21.4%. The survival of those patients in whom monocyte maturation was less than the normal range (less than 30.4%) was significantly shorter than the survival in those with normal maturation ( p less than 0.05). Four of the five patients whose initial maturation was less than 10% proved to be inoperable at surgery. Patients with extensive disease had monocyte maturation ranging from 2.4 to 52.9% with a median value of 13.2%, significantly lower than in those with limited disease (p less than 0.025). Patients with extensive disease and low monocyte maturation survived a significantly shorter time than those with normal maturation ( p less than 0.005). The depression of monocyte development may explain the finding of negative delayed hypersensitivity skin reactions in many patients with lung carcinoma and may prove useful as an index of prognosis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about the air-permeability of needled, stitched, and adhesively bonded non-woven webs in a 1976 issue.

Equations are given that relate the structure of spirally wrapped elastomeric-fibre core yams to their stretch properties. The model employed improves upon previous ones by considering the effect of covering-yarn diameter. Graphs are given that facilitate the use of the theory for manufacturing purposes. A comparison with available experimental data indicates an improved agreement between actual and predicted values of retraction in the most important case, where the input and output yam lengths are measured. It is expected that the improved theory given here will show to much greater advantage with the present commercial fine-core wrapped structures. In the special case where the wrapping or covering yarns have very low twist, the basic theory is inadequate. Modifications to account for compression of the cover yam are accordingly included to enable an approximate relationship between yam structure and stretch to be obtained in this case. [ABSTRACT FROM AUTHOR]

Copolymers and terpolymers, based on vinyl ethers from linseed conjugated fatty alcohols and selected as having the most potential for commercial use, were evaluated as chemically resistant coatings, metal-decorating coatings, small-applicance and architectural finishes, wire coatings, and adhesives. Studies show these materials to have promise in areas where a high-temperature baking schedule can be tolerated and where color is not of prime importance. Good compatibility with most commonly used pigments was observed. As wire coatings, film showed good continuity and had superior dielectric strength and resistance to cut-through; however, improvement in flexibility and adhesion to copper would be needed for successful application. Performance as adhesives was disappointing, since curing in the absence of air was poor. The polymers showed some promise as can coatings, but the need for modifications in them was demonstrated. [ABSTRACT FROM AUTHOR]

A 74 year old woman with mixed mitral valve disease presented with episodes of loss of consciousness and fainting. The attacks were noted to be closely related to posture, especially crouching, and this, with the clinical finding that the radial pulse disappeared before she lost consciousness, suggested the diagnosis of a ball valve thrombus. Cardiac catheterisation confirmed the diagnosis but was followed by a fall in blood pressure necessitating emergency surgery. The only position in which the circulation could be maintained was the right lateral, with steep head down tilt, and left femoro-femoral cardiopulmonary bypass had to be established in this position. Operation confirmed the presence of a ball valve thrombus and the patient recovered uneventfully. [ABSTRACT FROM PUBLISHER]

Two patients are described who complained of dyspnoea and systemic symptoms. They were found to have angio-immunoblastic lymphadenopathy with extensive pulmonary involvement. In both cases, high dose corticosteroid therapy led to relief of symptoms and clearing of the diffuse radiographic shadowing seen in both lung fields. [ABSTRACT FROM PUBLISHER]

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The article focuses on histochemical research on hemoglobin. In this study hyaline bodies found within 12 radicular odontogenic cysts were examined. Specimens were fixed in 10 percent neutral buffered formalin and embedded in paraffin. Information on the methods used for the stains and histochemical reactions for hemoglobin is provided.