Hermite-Gaussian mode detection via convolution neural networks.

Hermite-Gaussian (HG) laser modes are a complete set of solutions to the free-space paraxial wave equation in Cartesian coordinates and represent a close approximation to physically realizable laser cavity modes. Additionally, HG modes can be mode-multiplexed to significantly increase the information capacity of optical communication systems due to their orthogonality. Because cavity tuning and optical communication applications benefit from a machine vision determination of HG modes, convolution neural networks were implemented to detect the lowest 21 unique HG modes with an accuracy greater than 99%. As the effectiveness of a CNN is dependent on the diversity of its training data, extensive simulated and experimental data sets were created for training, validation, and testing.

Imaging skeletal muscle volume, density, and FDG uptake before and after induction therapy for non-small cell lung cancer.

AIM: To assess whether changes in body composition could be assessed serially using conventional thoracic computed tomography (CT) and positron-emission tomography (PET)/CT imaging in patients receiving induction chemotherapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: CT-based skeletal muscle volume and density were measured retrospectively from thoracic and lumbar segment CT images from 88 patients with newly diagnosed and untreated NSCLC before and after induction chemotherapy. Skeletal muscle 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake was measured from PET/CT images from a subset of patients (n=42). Comparisons of each metric before and after induction chemotherapy were conducted using the non-parametric Wilcoxon signed-rank test for paired data. The association between clinical factors and percentage change in muscle volume was examined using univariate linear regression models, with adjustment for baseline muscle volume. RESULTS: Following induction chemotherapy, thoracic (-3.3%, p=0.0005) and lumbar (-2.6%, p=0.0101) skeletal muscle volume were reduced (adiposity remained unchanged). The proportion of skeletal muscle with a density <0 HU increased (7.9%, p<0.0001), reflecting a decrease in skeletal muscle density and skeletal muscle FDG uptake increased (10.4-31%, p<0.05). No imaging biomarkers were correlated with overall survival. CONCLUSION: Changes in body composition can be measured from routine thoracic imaging. During chemotherapy skeletal muscle volume and metabolism are altered; however, there was no impact on survival in this retrospective series, and further validation in prospective, well-controlled studies are required.

Periprostatic adipose inflammation is associated with high-grade prostate cancer.

BACKGROUND: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown. METHODS: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives were to explore the clinical and systemic correlates of periprostatic WAT inflammation. Tumor characteristics and host factors including BMI, adipocyte diameter, and circulating levels of lipids, adipokines, and other metabolic factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher's exact tests, and generalized linear regression were used to examine the association between WAT inflammation and tumor and host characteristics. RESULTS: Periprostatic fat was collected from 169 men (median age 62 years; median BMI 28.3). Periprostatic WAT inflammation was identified in 49.7% of patients and associated with higher BMI (P=0.02), larger adipocyte size (P=0.004) and Gleason grade groups IV/V tumors (P=0.02). The relationship between WAT inflammation and high Gleason grade remained significant after adjusting for BMI (P=0.04). WAT inflammation correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to those without WAT inflammation (P's <0.05). CONCLUSION: Periprostatic WAT inflammation is common in this cohort of men with PC and is associated with high-grade PC.

Effect of aerobic training on the host systemic milieu in patients with solid tumours: an exploratory correlative study.

BACKGROUND: Few studies have investigated the effects of exercise on modulation of host factors in cancer patients. We investigated the efficacy of chronic aerobic training on multiple host-related effector pathways in patients with solid tumours. PATIENTS AND METHODS: Paired peripheral blood samples were obtained from 44 patients with solid tumours receiving cytotoxic therapy and synthetic erythropoietin (usual care; n=21) or usual care plus supervised aerobic training (n=23) for 12 weeks. Samples were characterised for changes in immune, cytokine and angiogenic factors, and metabolic intermediates. Aerobic training consisted of three supervised cycle ergometry sessions per week at 60% to 100% of peak oxygen consumption (VO2peak), 30-45 min per session, for 12 weeks following a nonlinear prescription. RESULTS: The between-group delta change in cardiopulmonary function was +4.1 ml kg (-1) min(-1), favouring aerobic training (P<0.05). Significant pre-post between-group differences for five cytokine and angiogenic factors (HGF, IL-4, macrophage inflammatory protein-1ß (MIP-1ß), vascular endothelial growth factor (VEGF), and TNF-α) also favour the aerobic training group (P's<0.05). These reductions occurred in conjunction with nonsignificant group differences for T lymphocytes CD4(+), CD8(+), and CD8(+)/CD45RA (P<0.10). For these factors, circulating concentrations generally increased from baseline to week 12 in the aerobic training group compared with decreases or no change in the usual care group. No significant changes in any metabolic intermediates were observed. CONCLUSIONS: Aerobic training alters host availability of select immune-inflammatory effectors in patients with solid tumours; larger confirmatory studies in more homogenous samples are warranted.

Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study.

The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior to allo-SCT was assessed in addition to the prognostic value of CPET-derived measures. CPET was performed prospectively on 21 patients with hematologic malignancies, with assessments of peak (for example, peak oxygen consumption, VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of cardiopulmonary function. No serious adverse events were observed during CPET procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak was 24.7±6.4 mL kg(-1 )min(-1) (range: 10.9-35.5), equivalent to 29%±17% below that of age-matched healthy controls. All patients proceeded with the conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During this period, 11 (52.4%) patients died (n=6, relapsed disease; n=5, non-relapse mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate analyses, both peak and submaximal markers of cardiopulmonary function were predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT were 0.89 (95% CI, 0.8-0.99, P=0.04) and 0.84 (95% CI, 0.71-0.98, P=0.03), respectively. In conclusion, CPET is safe and feasible prior to allo-SCT. Patients have marked impairments in cardiopulmonary function prior to allo-SCT. CPET-derived metrics may complement conventional measures to improve risk stratification.

Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial.

BACKGROUND: Bleomycin-etoposid-cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. METHODS: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice weekly sessions of four exercises, 3-4 sets/exercise of 10-15 repetitions at 12-15 repetition maximum load. The primary endpoint was muscle fibre size, assessed in muscle biopsies from musculus vastus lateralis. Secondary endpoints were fibre phenotype composition, body composition, strength, blood biochemistry and patient-reported endpoints. Healthy age-matched subjects (REF, n=19) performed the same RT-programme for comparison purposes. RESULTS: Muscle fibre size decreased by -322 µm(2) (95% confidence interval (CI): -899 to 255; P=0.473) in the CON-group and increased by +206 µm(2) (95% CI: -384 to 796; P=0.257) in the INT-group (adjusted mean difference (AMD), +625 µm(2), 95% CI: -253 to 1503, P=0.149). Mean differences in type II fibre size (AMD, +823 µm(2), P=0.09) and lean mass (AMD, +1.49 kg, P=0.07) in favour of the INT-group approached significance. The REF-group improved all muscular endpoints and had significantly superior changes compared with the INT-group (P<0.05). CONCLUSIONS: BEP was associated with significant reduction in lean mass and strength and trends toward unfavourable changes in muscle fibre size and phenotype composition. Resistance training was safe and attenuated dysfunction in selected endpoints, but BEP blunted several positive adaptations observed in healthy controls. Thus, our study does not support the general application of resistance training in this setting but larger-scaled trials are required to confirm this finding.

Muscle dysfunction in cancer patients.

BACKGROUND: Muscle dysfunction is a prevalent phenomenon in the oncology setting where patients across a wide range of diagnoses are subject to impaired muscle function regardless of tumor stage and nutritional state. Here, we review the current evidence describing the degree, causes and clinical implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented in oncology practice. Significant progress has been made over the last decade in the field of exercise oncology, indicating that exercise training constitutes a potent modulator of skeletal muscle function in patients with cancer. CONCLUSION: There are clear associations between muscle dysfunction and critical clinical end points. Yet there is a discrepancy between timing of exercise intervention trials, which can improve muscle function, and study populations in whom muscle function are proven prognostic important for clinical end points. Thus, future exercise trials should in early-stage patients, be powered to evaluate clinical outcomes associated with improvements in muscle function, or be promoted in advanced stage settings, aiming to reverse cancer-related muscle dysfunction, and thus potentially improve time-to-progression, treatment toxicity and survival.

Efficacy of multimodal exercise-based rehabilitation on physical activity, cardiorespiratory fitness, and patient-reported outcomes in cancer survivors: a randomized, controlled trial.

BACKGROUND: Sedentary behavior and impaired cardiovascular reserve capacity are common late effects of cancer therapy emphasizing the need for effective strategies to increase physical activity (PA) in cancer survivors. We examined the efficacy of a 12-month exercise-based rehabilitation program on self-reported PA, cardiorespiratory fitness (VO2peak), strength, and patient-reported outcomes. PATIENTS AND METHODS: Two hundred fourteen post-treatment cancer survivors were randomly assigned to a 12-month rehabilitation program consisting of individual (x3) and group-based (x6) counseling in combination with once weekly high-intensity group-based exercise training (the Copenhagen Physical Activity after Cancer Treatment, PACT; n = 108) or to a health evaluation program (HE, n = 106). Study outcomes were assessed at baseline, 6 months, and 12 months. RESULTS: After 12 months, the percentage of patients reporting meeting PA goal behavior (≥3 h/week) was significantly increased in the PACT group versus the HE group (70.4% versus 43.4%, P = 0.001). Repeated measures analyses indicated a statistically significant improvement in VO2peak (l min(-1)) in favour of PACT (treatment effect ratio = 1.04; 95% confidence interval 1.00-1.07; P = 0.032). Significant between group differences were also observed for strength (P < 0.001), depression (P = 0.020) and mental health (P = 0.040). CONCLUSION: A 12-month exercise-based rehabilitation program is an effective strategy to promote PA and improve VO2peak in cancer survivors.

Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function.

There is considerable utility in the use of transcranial Doppler ultrasound (TCD) to assess cerebrovascular function. The brain is unique in its high energy and oxygen demand but limited capacity for energy storage that necessitates an effective means of regional blood delivery. The relative low cost, ease-of-use, non-invasiveness, and excellent temporal resolution of TCD make it an ideal tool for the examination of cerebrovascular function in both research and clinical settings. TCD is an efficient tool to access blood velocities within the cerebral vessels, cerebral autoregulation, cerebrovascular reactivity to CO(2), and neurovascular coupling, in both physiological states and in pathological conditions such as stroke and head trauma. In this review, we provide: (1) an overview of TCD methodology with respect to other techniques; (2) a methodological synopsis of the cerebrovascular exam using TCD; (3) an overview of the physiological mechanisms involved in regulation of the cerebral blood flow; (4) the utility of TCD for assessment of cerebrovascular pathology; and (5) recommendations for the assessment of four critical and complimentary aspects of cerebrovascular function: intra-cranial blood flow velocity, cerebral autoregulation, cerebral reactivity, and neurovascular coupling. The integration of these regulatory mechanisms from an integrated systems perspective is discussed, and future research directions are explored.

Exercise therapy across the prostate cancer continuum.

Exercise has been increasingly investigated as an adjunct therapy for cancer patients. The purpose of this paper is to comprehensively review the literature regarding exercise as a therapeutic adjunct for prostate cancer (PC). Several studies in patients with PC have shown quality of life improvements associated with exercise. Although no study has established the effect of exercise as a monotherapy for PC, the molecular mechanisms responsible for the potential association between exercise and PC are being elucidated. Given the low-risk, high-reward nature of these studies, further investigations are needed to better define the function of exercise along the PC continuum.

Quartz crystal microbalance study of protein adsorption kinetics on poly(2-hydroxyethyl methacrylate).

The interaction of macromolecules with artificial biomaterials may lead to potentially serious complications upon implantation into a biological environment. The interaction of one of the most widely used biomaterials, polyHEMA, with lysozyme, bovine serum albumin (BSA), and lactoferrin was investigated using quartz crystal microbalance (QCM). The concentration dependence of adsorption was measured for the aforementioned proteins individually as well as for lysozyme-BSA, and lysozyme-lactoferrin combinations. An extension of Voinova's viscoelastic model to n layers was used to create thickness-time graphs for adsorption. For each of lactoferrin and lysozyme, two distinctly different timescales of adsorption could be differentiated. However, the mechanisms of adsorption appeared to differ between the two. Negative dissipation shifts were measured for low concentrations of lysozyme, trending to positive dissipation at higher concentrations. This suggested that lysozyme was adsorbed initially into the matrix, stiffening the hydrogel, and later onto the surface of polyHEMA. Additionally, trials with commercial no-rub cleaning solutions indicated little added effectiveness over buffer solutions. Mixtures of proteins showed behaviour which differed in some cases from the simple combination of single protein adsorption experiments.

Size-dependent denaturing kinetics of bovine serum albumin adsorbed onto gold nanospheres.

We have used localized surface plasmon resonance (LSPR) to monitor the kinetics of thermal denaturing of bovine serum albumin (BSA) adsorbed onto gold nanospheres of size 5 nm-100 nm. The effect of the protein on the LSPR was monitored by visible extinction spectroscopy. The wavelength of the peak extinction (resonance) is affected by the conformation of the adsorbed protein layer, and as such can be used as a very sensitive probe of thermal denaturing that is specific to the adsorbed (as opposed to free) protein. The time dependence of the denaturing is measured in the temperature range 60 degrees C-70 degrees C, and the lifetimes are used to calculate an activation barrier for thermal denaturing. The results show that thermally activated denaturing of proteins adsorbed onto nanoparticles has a nanoparticle-size-dependent activation barrier, and this barrier increases for decreasing particle size. This may have important implications for other protein-nanoparticle interactions.

Anomalous thermal denaturing of proteins adsorbed to nanoparticles.

We have used localized surface plasmon resonance (LSPR) to monitor the structural changes that accompany thermal denaturing of bovine serum albumin (BSA) adsorbed onto gold nanospheres of size 5nm-60nm. The effect of the protein on the LSPR was monitored by visible extinction spectroscopy. The position of the resonance is affected by the conformation of the adsorbed protein layer, and as such can be used as a very sensitive probe of thermal denaturing that is specific to the adsorbed protein. The results are compared to detailed calculations and show that full calculations can lead to significant increases in knowledge where gold nanospheres are used as biosensors. Thermal denaturing on spheres with diameter > 20 nm show strong similarity to bulk calorimetric studies of BSA in solution. BSA adsorbed on nanospheres with d [Symbol: see text] 15nm shows a qualitative difference in behavior, suggesting a sensitivity of denaturing characteristics on local surface curvature. This may have important implications for other protein-nanoparticle interactions.

Exercise preferences among a population-based sample of non-Hodgkin's lymphoma survivors.

In the present study, we examined the exercise preferences of a population-based sample of non-Hodgkin's lymphoma (NHL) survivors. A secondary purpose was to explore the association between various demographic, medical, and exercise behaviour variables and elicited exercise preferences. Using a retrospective survey design, 431 NHL survivors residing in Alberta, Canada completed a mailed questionnaire designed to assess exercise preferences, past exercise behaviour, and various demographic variables. Overall, 77% of participants preferred or maybe preferred to receive exercise counselling at some point after their NHL diagnosis. An overwhelming majority indicated that they would possibly be interested (81%) and able (85%) to participate in an exercise programme designed for NHL survivors. The majority of participants (55%) listed walking as their preferred choice of exercise. Logistic regression analyses indicated that NHL survivors' exercise preferences were influenced by body mass index (BMI), exercise behaviour, and gender. Eliciting exercise preferences from the population in question yields important information for cancer care professionals designing exercise programmes for NHL survivors. Furthermore, tailoring exercise programmes to the preferences of NHL survivors may be one method to potentially enhance exercise adherence in this population both inside and outside of clinical trials.

Rhodamine-123: therapy for hormone refractory prostate cancer, a phase I clinical trial.

Rhodamine-123, a lipophilic, cationic, rhodocyanine dye, has been reported to have carcinoma selective toxicity in vitro and in vivo. This phase I clinical trial established the safety and pharmacokinetics of Rhodamine-123 administered to men with hormone refractory prostate cancer. A single dose toxicity study of Rhodamine-123 determined the maximum tolerated dose. A multiple dose toxicity study assessed the safety of Rhodamine-123 at the maximum tolerated dose level. Transient and variable toxicities noted following Rhodamine-123 infusion resolved within 6 hours following infusion. Pharmacokinetic analyses of sera showed no accumulation of drug with repeated monthly administrations. Drug retention was confirmed in prostatic tissue following Rhodamine-123 administration. PSA doubling times lengthened variably suggesting drug efficacy but the data were not statistically significant. The maximum tolerated dose of Rhodamine-123 is 96 mg/m2. The drug can be safely administered at monthly intervals without detectable drug accumulation in serum. Rhodamine-123 is retained by prostatic tumor tissue.

In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials.

The in vitro uptake and release behaviour of cromolyn sodium, ketotifen fumarate, ketorolac tromethamine and dexamethasone sodium phosphate with silicon-containing (lotrafilcon and balafilcon) and p-HEMA-containing (etafilcon, alphafilcon, polymacon, vifilcon and omafilcon) hydrogel contact lenses indicated that both drug and material affected the uptake and release behaviour. Rapid uptake and release (within 50 min) was observed for all drugs except ketotifen fumarate which was more gradual taking approximately 5h. Furthermore, the maximum uptake differed significantly between drugs and materials. The highest average uptake (7879+/-684 microg/lens) was cromolyn sodium and the lowest average uptake (67+/-13 microg/lens) was dexamethasone sodium phosphate. Partial release of the drug taken up was observed for all drugs except dexamethasone sodium phosphate where no release was detected. Sustained release was demonstrated only by ketotifen fumarate. Drug uptake/release appeared to be a function of lens material ionicity, water and silicon content. The silicon-containing materials released less drug than the p-HEMA-containing materials. The lotrafilcon material demonstrated less interactions with the drugs than the balafilcon material which can be explained by their different bulk composition and surface treatment.

Ciprofloxacin interaction with silicon-based and conventional hydrogel contact lenses.

PURPOSE: Hydrogel contact lenses can be used as bandage lenses to protect the corneal surface after injury. The use of novel silicon-based hydrogel lens materials as bandage lenses has not gained widespread acceptance. As a first step toward advocating their usefulness as bandage lenses, their interaction with ocular pharmaceuticals must be understood because topical agents are often administered in conjunction with bandage lenses. METHODS: The in vitro uptake and release of ciprofloxacin from silicone-based hydrogel (SH) and conventional pHEMA-based (CH) hydrogel contact lenses was examined by spectrophotometric evaluation of the drug concentration in saline solution. RESULTS: The hydrogel contact lenses tested showed similar drug uptake (average 1800 microg/lens) but different levels of drug release. Multiphoton laser microscopy indicated that ciprofloxacin was distributed throughout the lens thickness, with higher levels of drug at the surface owing to drug precipitation. The drug adsorption onto the lenses was partially reversible. The SH lenses released a lower amount of drug than CH lenses (72 vs. 168 microg/lens). Ionic lenses released less drug than non-ionic lenses (127 vs. 151 microg/lens). CONCLUSIONS: The differences in ciprofloxacin uptake and release between SH and CH materials may not be clinically significant because the amount of drug released from all lenses would be above the MIC(90) of ciprofloxacin for common ocular pathogens. These results indicate that material properties have a significant impact on drug-lens interactions.

A randomized trial of exercise and quality of life in colorectal cancer survivors.

We conducted a randomized controlled trial to determine the effects of a home-based exercise intervention on change in quality of life (QOL) in recently resected colorectal cancer survivors, most of whom were receiving adjuvant therapy. Participants were randomly assigned in a 2:1 ratio to either an exercise (n = 69) or control (n = 33) group. The exercise group was asked to perform moderate intensity exercise 3-5 times per week for 20-30 min each time. The primary outcome was change in QOL as measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale. Adherence in the exercise group was good (75.8%) but contamination in the control group was problematic (51.6%). Intention-to-treat analysis revealed no significant differences between groups for change in the FACT-C (mean difference, -1.3; 95% CI, -7.8 to 5.1; P = 0.679). In an 'on-treatment' ancillary analysis, we compared participants who decreased versus increased their cardiovascular fitness over the course of the intervention. This analysis revealed significant differences in favour of the increased fitness group for the FACT-C (mean difference, 6.5; 95% CI, 0.4-12.6; P = 0.038). These data suggest that increased cardiovascular fitness is associated with improvements in QOL in colorectal cancer survivors but better controlled trials are needed.

Non-inflammatory corneal complications of contact lens wear.

Contact lenses can induce changes in the epithelium, stroma and endothelium of the cornea, all of which can be observed clinically using the slit-lamp biomicroscope. These complications include epithelial microcysts, vacuoles and staining, stromal oedema and vascularization, and endothelial polymegethism and blebs. Each complication can be attributed to one or more aetiological factors such as hypoxia, hypercapnia, tissue acidosis, trauma, hypersensitivity and toxicity. This review outlines the way in which these complications manifest clinically, and consideration is given to management strategies and likely prognoses. Early detection of these conditions and appropriate action can usually prevent more serious ocular complications.

Coping with cancer: can exercise help?

A comprehensive review of the recent literature reveals that exercise has a positive effect on a broad range of quality-of-life parameters after patients are diagnosed as having cancer. The general exercise prescription is moderate-intensity exercise, 3 to 5 days per week, 20 to 30 minutes per session. Conditions that warrant prescription modification include fatigue periods during treatment, acute or chronic physical impairments that may have resulted from surgery or adjuvant therapy, and the presence of bone cancer. Research suggests that physicians who prescribe exercise improve motivation and adherence in their patients who have cancer.