TopoGeoFusion: Integrating object topology based feature computation methods into geometrical feature analysis to enhance classification performance.

This study used smartphone captured RGB images of gooseberries to automatically sort into standard, premium, or rejected categories based on topology. Main challenges addressed include, separation of touching or overlapping fruits into individual entities and new method called 'TopoGeoFusion' that combines basic geometrical features with topology aware features computed from the fruits to assess the grade or maturity. Quality assessment helps in grading the fruit to determine market suitability and intelligent camera applications. Computer Vision-based techniques have been applied to automatically grade the quality of gooseberries as standard, premium, or rejected according to fruit maturity. Smartphone-captured images of 1697 Indian Star Gooseberries are contributed to the study. This work acquired images consisting multiple fruits with overlapping and non-overlapping boundaries for concurrent quality assessment. Multiple classifiers such as Random Forest, SVM, Naive Bayes, Decision Tree, and KNN were applied to grade the gooseberry fruit. Random Forest classification with a fusion feature model resulted in an accuracy of 100 % towards reject, standard, and premium classes for test sets with four training strategies. The proposed segmentation model proves reliable in fruit detection & extraction with an average mAP of 0.56, resulting in an acceptable model for grade assessment.•The study highlights the effectiveness of TopoGeoFusion in automating the grading process of gooseberry fruits using topologically computed features.•The developed models exhibit high accuracy and reliability, even in challenging scenarios such as overlapping and touching fruits.•The method provides the technique to detect and extract the occluded objects and compute the features based on the partial object's topology.

Impressive neurological recovery following C-spine dislocation in a patient on long term immunosuppression.

We report excellent neurological improvement in a patient with C6/C7 dislocation following a high speed road traffic accident. This case in particular is unusual because the patient was the recipient of an organ transplant during childhood and was therefore on long term immunosuppressant medication at the time of injury. In this report we reflect on the role of steroid use in traumatic spinal cord injury and put our case within the context of current evidence and this unusual clinical scenario.

ARM-microcontroller based portable nitrite electrochemical analyzer using cytochrome c reductase biofunctionalized onto screen printed carbon electrode.

Nitrite (NO2-) supplementation limits hypoxia-induced oxidative stress and activates the alternate NO pathway which may partially account for the nitrite-mediated cardioprotection. So, sensitive and selective biosensors with point-of-care devices need to be explored to detect the physiological nitrite level due to its important role in human pathophysiology. In this work, cytochrome c reductase (CcR) biofunctionalized self assembled monolayer (SAM) functionalized on gold nanoparticles (GNPs) in polypyrrole (PPy) nanocomposite onto the screen printed carbon electrode (SPCE) was investigated as a biosensor for the detection of nitrite based on its electrochemical and catalytic properties. CcR was covalently coupled with SAM layers on GNPs by using EDC and NHS. Direct electrochemical response of CcR biofunctionalized electrodes showed a couple of well-defined and nearly reversible cyclic voltammetric peaks at -0.34 and -0.45 vs. Ag/AgCl. Under optimal conditions, the biosensor could be used for the determination of NO2- with a linear range from 0.1-1600µm and a detection limit of 60nM with a sensitivity of 0.172µAµM-1cm-2. Further, we have designed and developed a novel and cost effective portable electrochemical analyzer for the measurement of NO2- in hypoxia induced H9c2 cardiac cells using ARM microcontroller. The results obtained here using the developed portable electrochemical nitrite analyzer were also compared with the standard cyclic voltammetry instrument and found in agreement with each other.

Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data.

BACKGROUND: In the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator). METHODS: Since an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan-Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted. RESULTS: For both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences. CONCLUSIONS: To our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma.

Oral paracetamol versus oral ibuprofen for closure of haemodynamically significant patent ductus arteriosus in preterm neonates (<32 weeks): a blinded, randomised, active-controlled, non-inferiority trial.

INTRODUCTION: Haemodynamically significant patent ductus arteriosus (hsPDA) is a common cause of mortality and morbidity in preterm infants. Existing medical therapies with ibuprofen or indomethacin have multiple adverse effects. Hence, an alternative drug like paracetamol given through oral route with less side effects need to be tested in an appropriate study design with least risk of bias to arrive at a conclusion. METHODS AND ANALYSIS: Multisite, randomised, active-controlled, non-inferiority design. The primary objective is to study the efficacy of oral paracetamol for closure of hsPDA in comparison to oral ibuprofen in preterm neonates of <32 weeks' gestation. Randomisation web-based and allocation concealment would be done; the treating team, investigators, outcome assessors and laboratory personnel would be blinded from the intervention. Echocardiography images would be coded for independent review. Closure of PDA by the end of last dose of study drug or earlier would be the study endpoint. A sample size of 196 neonates would be enrolled with a non-inferiority margin of 15%. Both intention-to-treat and per-protocol analysis will be done to assess the effect of contamination and protocol violations in the primary outcome. ETHICS AND DISSEMINATION: The trial would follow international code of ethics for clinical trial. The trial protocol was approved by the Institute Ethics Committee of all three centres. All serious adverse events would be reported in detail to the Institute Ethics Committee. A written informed consent would be obtained from one of the parents. No plan has been made for dissemination. TRIAL REGISTRATION NUMBER: CTRI/2014/08/004805.

Naringenin Ameliorates Doxorubicin Toxicity and Hypoxic Condition in Dalton's Lymphoma Ascites Tumor Mouse Model: Evidence from Electron Paramagnetic Resonance Imaging.

Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2.5 mg/kg) treated, and DOX (2.5 mg/kg) + NAR (50 mg/kg/d) treated. DOX administration significantly altered the levels of functional markers in blood and antioxidant enzymes in kidney, heart, lung, liver, spleen, and tumor tissues. These changes in antioxidant enzymes and successive lipid peroxidation were prevented by NAR supplementation, resulting in decreases in the risk of toxicity due to DOX therapy. Histopathology results and electron paramagnetic resonance imaging (EPRI) of the tumor microenvironment confirmed this evidence. Using EPRI, pharmacokinetics of the nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3-CP) was monitored intratumorally before and after chemotherapy. EPRI of the DOX + NAR-treated mouse model showed reduced tumor size with significant modification of the hypoxic condition inside the tumor microenvironment. Consequently, these findings suggest that NAR treatment significantly reduces DOX-induced toxicity and the hypoxic condition in a DLA tumor-bearing mouse model.

Cost and consequences of noncompliance to oral bisphosphonate treatment.

BACKGROUND: Despite the favorable efficacy, safety, and cost-effectiveness profile of bisphosphonate (BIS) treatment for osteoporosis (OP), patient compliance remains suboptimal. A longer follow-up period could help to better characterize patient behavior as well as the predictors of noncompliance because of the extended durations of osteoporosis and time to a fracture. OBJECTIVE: To determine health care outcomes associated with compliance and noncompliance to BIS therapy in women diagnosed with OP. METHODS: This retrospective claims study focused on women with OP, who were aged 55 years and older and using oral BIS treatment. Patients were identified within the HealthCore Integrated Research Environment (HIRE) between January 1, 2007, through June 30, 2010. Patients were required to have ≥ 12 months of pre-index eligibility and ≥ 24 months of post-index health plan eligibility. Post-index eligibility was split into 2 periods: (1) the compliance time period (the first 12-month post-index period, in which compliance was determined) and (2) the cost and consequences time period (13- to 24-month post-index period during which time health care resource utilization, cost, and outcomes were assessed). Noncompliance was defined as medical possession ratio (MPR) less than 70%. Descriptive statistics described outcome variables for the study population. A logistic regression model determined variables predictive of compliance. Further, a generalized linear model was used to examine associations between all-cause or OP-related medical/total costs and to estimate health care utilization. RESULTS: Of patients overall (N = 27,905), 59% were noncompliant, and 62% discontinued medication. Among noncompliant patients, 6.7% switched BIS therapy (after 64 days average); 97% discontinued (87 days average); and 21% restarted medication (218 days average). Of noncompliant patients, 14% had greater than 1 inpatient visits; 16% had greater than 1 emergency room visits; 94% had greater than 1 outpatient visits; and 95% had greater than 1 office visits. Logistic regression results indicated that under aged 65 years (P = 0.012) predicted noncompliance. Relative to the compliant group, noncompliant patients had higher fracture rates at post-index second year, 3.3% vs. 2.4%, and combined second and third years, 6.0% vs. 4.8%, respectively. Compared with noncompliant patients, compliant patients had 9% (P = 0.007) lower OP-related costs, 3% lower all-cause costs during the second post-index year, and 11% (P = 0.016) lower OP-related costs. Mean 13- to 24-month post-index period all-cause costs were $7,237 for noncompliant patients versus $6,758 for compliant patients (P = 0.008). CONCLUSIONS: These results indicate high noncompliance rates in this population of older females. OP medication compliance was associated with lower fracture rates, OP- and all-cause costs, and health care utilization. These findings highlight the financial implications and treatment outcomes of BIS medication noncompliance within a female osteoporotic population.

Safe removal of long-term venous catheters in the neck.

AIMS: Tunnelled venous catheters are a well-established method of long-term venous access for total parental nutrition, chemotherapy and antimicrobial treatment. Removal of these catheters is a simple procedure; however, there are some significant risks. METHODS: We report a case in which a serious complication occurred. A simple technique for the safe removal of long-term venous catheters is described. CONCLUSION: A direct surgical removal is now generally favoured for safe line removal. However, this still carries the same complications and care must be taken in the technique.

Virtual electrochemical nitric oxide analyzer using copper, zinc superoxide dismutase immobilized on carbon nanotubes in polypyrrole matrix.

In this work, we have designed and developed a novel and cost effective virtual electrochemical analyzer for the measurement of NO in exhaled breath and from hydrogen peroxide stimulated endothelial cells using home-made potentiostat. Here, data acquisition system (NI MyDAQ) was used to acquire the data from the electrochemical oxidation of NO mediated by copper, zinc superoxide dismutase (Cu,ZnSOD). The electrochemical control programs (graphical user-interface software) were developed using LabVIEW 10.0 to sweep the potential, acquire the current response and process the acquired current signal. The Cu,ZnSOD (SOD1) immobilized on the carbon nanotubes in polypyrrole modified platinum electrode was used as the NO biosensor. The electrochemical behavior of the SOD1 modified electrode exhibited the characteristic quasi-reversible redox peak at the potential, +0.06 V vs. Ag/AgCl. The biological interferences were eliminated by nafion coated SOD1 electrode and then NO was measured selectively. Further, this biosensor showed a wide linear range of response over the concentration of NO from 0.1 µM to 1 mM with a detection limit of 0.1 µM and high sensitivity of 1.1 µA µM(-1). The electroanalytical results obtained here using the developed virtual electrochemical instrument were also compared with the standard cyclic voltammetry instrument and found in agreement with each other.

Retrospective US database analysis of drug utilization patterns, health care resource use, and costs associated with adjuvant interferon alfa-2b therapy for treatment of malignant melanoma following surgery.

BACKGROUND: The purpose of this study was to identify a real-world US population having undergone surgery for malignant melanoma and describe treatment patterns, health care resource utilization, and costs for patients who subsequently received interferon alfa-2b (IFN) therapy or other standard of care chemotherapies. METHODS: A retrospective cohort study was conducted using administrative claims from MarketScan(®) databases among melanoma patients diagnosed between 2004 and 2008 who had surgery and were subsequently treated with IFN or other chemotherapies. Health care resource utilization and costs of services (converted to 2009 dollars) were evaluated. Cost refers to the amount paid to providers associated with the health service. RESULTS: Of 18,075 subjects with melanoma surgery claims, 1525 (8.4%) were treated with IFN and 1194 (6.6%) with other chemotherapies. Median duration (days) and number of doses of IFN therapy were 29 and 20, respectively. Approximately half of patients who received IFN discontinued therapy within or after the one-month induction phase. For IFN therapy patients, average total cost per patient for the last melanoma-related surgery prior to start of therapy, including costs of the surgery itself, pathology, anesthesia, and hospital care, was $2219. The average total cost per patient related to IFN therapy was $1188; this included costs for drug, office visits, blood work, and infusions. Other chemotherapy costs ranged from $146 to $2678. CONCLUSION: There is an unmet treatment need, considering that this study observed that melanoma patients on IFN therapy post-surgery do not complete the recommended one-year course of treatment which may compromise its full therapeutic benefits. Further study to investigate reasons for discontinuation may be warranted. In addition, costs associated with adjuvant IFN therapy in post-surgical treatment of disease are likely acceptable.

Quality of Life and Utility in Patients with Metastatic Soft Tissue and Bone Sarcoma: The Sarcoma Treatment and Burden of Illness in North America and Europe (SABINE) Study.

The aim of the study was to assess health-related quality of life (HRQoL) among metastatic soft tissue (mSTS) or bone sarcoma (mBS) patients who had attained a favourable response to chemotherapy. We employed the EORTC QLQ-C30, the 3-item Cancer-Related Symptoms Questionnaire, and the EQ-5D instrument. HRQoL was evaluated overall and by health state in 120 mSTS/mBS patients enrolled in the SABINE study across nine countries in Europe and North America. Utility was estimated from responses to the EQ-5D instrument using UK population-based weights. The mean EQ-5D utility score was 0.69 for the pooled patient sample with little variation across health states. However, patients with progressive disease reported a clinically significant lower utility (0.56). Among disease symptoms, pain and respiratory symptoms are common. This study showed that mSTS/mBS is associated with reduced HRQoL and utility among patients with metastatic disease.

Effects of yogurt and applesauce on the oral bioavailability of nilotinib in healthy volunteers.

Nilotinib, a potent orally bioavailable BCR-ABL tyrosine kinase inhibitor, is currently available as a hard gelatin capsule that must be swallowed whole. For patients who may have difficulty swallowing the intact capsule, an alternative mode of administration is desirable. The authors compared the bioavailability of nilotinib from the following administrations in 48 healthy subjects: (1) 400 mg nilotinib given as two 200-mg nilotinib intact capsules; (2) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of nonfat plain yogurt; and (3) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of applesauce. Nilotinib absorption was modestly increased following the administration of nilotinib dispersed in yogurt. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 1.31 (1.22-1.41), 1.11 (1.05-1.16), and 1.08 (1.02-1.15), respectively. Administration of nilotinib dispersed in applesauce showed equivalent bioavailability compared with administration of nilotinib as intact capsules. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.95 (0.88-1.02), 0.99 (0.94-1.04), and 0.97 (0.90-1.03), respectively. Each treatment was well tolerated in the study subjects. The data support a feasible alternative method of nilotinib administration; each capsule's contents may be dispersed in 1 teaspoon of applesauce and taken immediately.

Joint variable selection for fixed and random effects in linear mixed-effects models.

It is of great practical interest to simultaneously identify the important predictors that correspond to both the fixed and random effects components in a linear mixed-effects (LME) model. Typical approaches perform selection separately on each of the fixed and random effect components. However, changing the structure of one set of effects can lead to different choices of variables for the other set of effects. We propose simultaneous selection of the fixed and random factors in an LME model using a modified Cholesky decomposition. Our method is based on a penalized joint log likelihood with an adaptive penalty for the selection and estimation of both the fixed and random effects. It performs model selection by allowing fixed effects or standard deviations of random effects to be exactly zero. A constrained expectation-maximization algorithm is then used to obtain the final estimates. It is further shown that the proposed penalized estimator enjoys the Oracle property, in that, asymptotically it performs as well as if the true model was known beforehand. We demonstrate the performance of our method based on a simulation study and a real data example.

Bayesian variable selection using an adaptive powered correlation prior.

The problem of selecting the correct subset of predictors within a linear model has received much attention in recent literature. Within the Bayesian framework, a popular choice of prior has been Zellner's g-prior which is based on the inverse of empirical covariance matrix of the predictors. An extension of the Zellner's prior is proposed in this article which allow for a power parameter on the empirical covariance of the predictors. The power parameter helps control the degree to which correlated predictors are smoothed towards or away from one another. In addition, the empirical covariance of the predictors is used to obtain suitable priors over model space. In this manner, the power parameter also helps to determine whether models containing highly collinear predictors are preferred or avoided. The proposed power parameter can be chosen via an empirical Bayes method which leads to a data adaptive choice of prior. Simulation studies and a real data example are presented to show how the power parameter is well determined from the degree of cross-correlation within predictors. The proposed modification compares favorably to the standard use of Zellner's prior and an intrinsic prior in these examples.