Supply Chain Management (SCM) systems require time sequencing, coordination and tracking the movement of goods and processes. Internet of Things (IoT) and Blockchain technologies are useful to ...develop a secure automated SCM. IoT devices with in-built sensors and actuators help to keep track of the state, location, temperature or other parameters of an entity, and control the automation of routine as well as hazardous tasks. Blockchain technology supports time-stamping, authentication, process coordination, non-repudiation, commercial transactions, and also provides security for transactions and storage. The pharmaceutical SCM demands accurate, immediate and secure control system. Additionally, the supply chain process data from IoTs is stored and processed in Cloud by Analytics applications, for business planning and improvement. An efficient and secure IoT-Cloud-Blockchain based system for both SCM automation and analytics has been proposed in this work. It leverages a hierarchical IoT, Mist, Edge, Fog, Cloud computing (IMEFC) architecture to enhance Communication-Response-Compute-Security-Storage (CRCSS) in the system. Blockchain technology provides security for the SCM transactions and data. The efficiency of the Blockchain is measured in terms of upload time, download time and transaction fees for Bitcoin, Ethereum and Filecoin platforms. The Filecoin blockchain platform is quicker and cost-effective for larger file sizes, compared to Ethereum and Bitcoin, making it suitable for Pharmaceutical SCM systems.
The ab initio atom-centered density matrix propagation (ADMP) method has been employed to study the dynamics of protonated water clusters of various sizes. An interesting result that hints at the ...possible amphiphilicity of the hydronium ion is detected. The hydrated proton tends to reside on the surface of the water clusters studied, with the lone pair on the protonated oxygen pointing “outwards” from the cluster. It is also noted that the hopping rate and average bonding topology in the local vicinity of the protonated species show a pronounced difference when treated with B3LYP and BLYP functionals. This is proposed to be on account of the potential for greater electronic exchange interactions in the vicinity of the positive charge.
Background
Cancer cachexia is frequently documented by self‐reported, single time‐point weight histories. This approach lacks the granularity needed to fully elucidate the progression of cachexia ...syndrome. This study aimed to longitudinally assess body weight changes pre‐ and post‐cancer diagnosis in gastrointestinal (GI) cancer patients.
Methods
Body weights and relevant clinical data recorded in the electronic health record 12 months pre‐ and post‐GI cancer (colorectal, gastroesophageal, hepatobiliary and pancreatic) diagnosis were extracted. Weight loss was categorized by the International Consensus Definition for cachexia.
Results
A total of 879 patients were included in the final cohort including patients diagnosed with colorectal (n = 317), hepatocellular (n = 185), biliary (n = 72), pancreatic (n = 186) or gastroesophageal (n = 119) cancer. Stage of disease was equally distributed. Patients without cachexia at diagnosis (n = 608) remained weight stable during the 12 months pre‐diagnosis (+0.5 ± 0.5% body weight; P = 0.99). Patients with cachexia at diagnosis (n = 271) remained weight stable 6 to 12 months prior to diagnosis (+0.4 ± 0.8%; P > 0.9999) and lost 8.7 ± 0.6% (P < 0.0001) within the 6 months pre‐diagnosis. Patients without cachexia at diagnosis lost more weight post‐diagnosis (6.3 ± 0.6%) than patients with cachexia at diagnosis (4.7 ± 1.0%; P = 0.01). Pre‐diagnosis weight trajectories did not differ between primary malignancies or stage of disease in patients without or with cachexia at diagnosis (all P ≥ 0.05). Post‐diagnosis weight trajectories did differ by primary malignancy (P ≤ 0.0002) and stage (P < 0.0001). In both patients without and with cachexia at diagnosis, colorectal patients lost the least amount of weight post‐diagnosis and gastroesophageal patients lost the most amount of weight post‐diagnosis. Stage 4 patients without or with cachexia at diagnosis lost the most weight post‐diagnosis (P ≤ 0.0003). Regardless of cachexia status at diagnosis, patients lost more weight when treated with systemic therapy (7.1 ± 0.7%; P < 0.0001; n = 419) or radiation therapy (8.4 ± 1.4%; P = 0.02; n = 116) compared to those who did not. Patients who did not have surgery lost more weight post‐diagnosis (7.6 ± 1.1%; P < 0.0001; n = 355) compared to those who did have surgery. By 12 months post‐diagnosis, 83% of the surviving GI cancer patients in this cohort had transitioned into cachexia syndrome.
Conclusions
Significant weight loss in patients with GI cancer cachexia at diagnosis initiates at least 6 months prior to diagnosis, and most patients will transition into cachexia syndrome post‐diagnosis, regardless of pre‐diagnosis weight change and stage of disease. These findings punctuate the importance of weight surveillance in cancer detection and earlier palliative interventions post‐diagnosis in the GI cancer patient population.
Introduction:
Autism is included as a certifiable disability in the Indian Rights of Persons with Disability Act, 2016. The Indian Scale for Assessment of Autism (ISAA), developed by the Government ...of India and mandated for certifying disability, is a detailed instrument that needs trained mental health experts and takes time to administer. The current project was planned to develop a simple, easy to use screening tool based on the ISAA to identify possible cases in the community.
Methods:
The project is planned in three phases. During the first phase, data collected during the development of the ISAA (N = 433/436 children with autism) will be used to identify questions answered as frequently, mostly, and always. During the second phase, the psychometric properties of the screening tool based on these items will be evaluated among research participants recruited from hospitals and special schools (n = 100). In the third phase, the screening questionnaire will be administered in the community (n = 500).
Results:
The most frequently answered questions will be selected for inclusion in the proposed screening tool. The number of items in the screening tool will be kept as few as possible, with yes or no responses
Discussion:
Indian Autism Screening Questionnaire (IASQ) will be tested as a screening version of ISAA, which can be used by community health workers, teachers, or school counselors. The IASQ will not provide a diagnosis of autism. A positive screening result should be followed by a thorough assessment by a trained specialist. Analyzing the psychometric properties of the test can help ensure cost-effective screening of the community to identify autism.
To assess predictors and moderators of a cognitive-behavioral prevention (CBP) program for adolescent offspring of parents with depression.
This 4-site randomized trial evaluated CBP compared to ...usual community care (UC) in 310 adolescents with familial (parental depression) and individual (youth history of depression or current subsyndromal symptoms) risk for depression. As previously reported by Garber and colleagues, a significant prevention effect favored CBP through 9 months; however, outcomes of CBP and UC did not significantly differ when parents were depressed at baseline. The current study expanded on these analyses and examined a range of demographic, clinical, and contextual characteristics of families as predictors and moderators and used recursive partitioning to construct a classification tree to organize clinical response subgroups.
Depression onset was predicted by lower functioning (hazard ratio HR = 0.95, 95% CI = 0.92-0.98) and higher hopelessness (HR = 1.06, 95% CI = 1.01-1.11) in adolescents. The superior effect of CBP was diminished when parents were currently depressed at baseline (HR = 6.38, 95% CI = 2.38-17.1) or had a history of hypomania (HR = 67.5, 95% CI = 10.9-417.1), or when adolescents reported higher depressive symptoms (HR = 1.04, 95% CI = 1.00-1.08), higher anxiety (HR = 1.05, 95% CI = 1.01-1.08), higher hopelessness (HR = 1.10, 95% CI = 1.01-1.20), or lower functioning (HR = 0.94, 95% CI = 0.89-1.00) at baseline. Onset rates varied significantly by clinical response cluster (0%-57%).
Depression in adolescents can be prevented, but programs may produce superior effects when timed at moments of relative wellness in high-risk families. Future programs may be enhanced by targeting modifiable negative clinical indicators of response.
Prevention of Depression in At-Risk Adolescents; http://clinicaltrials.gov/; NCT00073671.
In recent years, the incidence of thyroid cancer has increased dramatically, resulting in an increased demand for early thyroid nodule examination. Ultrasound (US) imaging is the modality most ...frequently used to image thyroid nodules; However, the low image resolution, speckle noise, and high variability make it difficult to utilize traditional image processing techniques. Recent advances in deep learning (DL) have increased research into the automated processing of thyroid US images. We review three main image processing tasks for thyroid nodule analysis: classification, segmentation, and detection. We discuss the advantages and limitations of the recently proposed DL techniques as well as the data availability and algorithmic efficacy. In addition, we investigate the remaining obstacles and future potential for automated analysis of thyroid US images.
The oral thrombopoietin receptor agonist eltrombopag is approved for treatment of adults with chronic immune thrombocytopenia. In the PETIT trial, we aimed to investigate the efficacy and safety of ...eltrombopag in children with persistent or chronic immune thrombocytopenia.
PETIT was a three-part, randomised, multicentre, placebo-controlled study done at 22 centres in the USA, UK, Canada, Spain, France, and the Netherlands. Patients aged 1-17 years with immune thrombocytopenia lasting for 6 months or longer and platelets less than 30 × 10(9) per L who had received at least one previous treatment were enrolled. We enrolled patients into three cohorts consisting of patients aged 12-17, 6-11, and 1-5 years. We established patients' starting doses with an open-label, dose-finding phase with five patients in each cohort. During the dose-finding phase, patients aged 6-17 years started eltrombopag at 25 mg once per day (12·5 mg for those weighing <27 kg) and patients aged 1-5 years received 0·7 mg/kg per day to a maximum of 2 mg/kg unless otherwise approved. We permitted dose adjustments on the basis of platelet response up to a maximum dosage of 75 mg per day. Additional patients were then recruited and randomly assigned (2:1) to receive either eltrombopag or placebo tablets (or oral suspension formulation if aged 1-5 years) once per day for 7 weeks at the previously established doses. Starting doses for the double-blind phase were 37·5 mg/day for patients aged 12-17 years; 50 mg/day for patients weighing 27 kg or more (25 mg for east Asian patients) and 25 mg/day for patients weighing less than 27 kg (12·5 mg once per day for east Asian patients) for patients aged 6-11 years; and 1·5 mg/kg once per day (0·8 mg/kg once per day for east Asian patients) for patients aged 1-5 years. Randomisation was done by the GlaxoSmithKline Registration/Medication Ordering System and both patients and study personnel were masked to treatment assignments. Patients who completed treatment were then enrolled into an open-label phase and all patients could receive up to 24 weeks of eltrombopag. The primary outcome was the proportion of patients achieving a platelet count of 50 × 10(9) per L or more at least once from weeks 1-6 (days 8 to 43) of the randomised phase of the study in the absence of rescue therapy. We assessed efficacy in the intent-to-treat population, which consisted of all patients assigned to treatment, and we assessed safety in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT00908037.
Between Oct 2, 2009, and June 22, 2011, we recruited 15 patients, with five patients in each age cohort, into the open-label dose-finding phase who did not progress into the double-blind phase. From March 17, 2010, to Jan 15, 2013, we randomly assigned 67 patients to treatment, with 45 patients assigned to receive eltrombopag (16 children aged 12-17 years, 19 aged 6-11 years, and ten aged 1-5 years) and 22 to receive placebo (eight children aged 12-17 years, nine aged 6-11 years, and five aged 1-5 years). However, two patients assigned to receive eltrombopag did not receive the study drug and one was lost to follow-up, and one patient assigned to receive placebo was given eltrombopag. From weeks 1 to 6, 28 (62%) patients who received eltrombopag, compared with seven (32%) who received placebo, achieved the primary endpoint of platelet count 50 × 10(9) per L or more at least once without rescue (odds ratio 4·31, 95% CI 1·39-13·34, p=0·011). The most common adverse events with eltrombopag were headache (13 30% patients receiving eltrombopag vs nine 43% patients receiving placebo), upper respiratory tract infection (11 25% patients vs two 10% patients), and diarrhoea (seven 16% patients vs one 5% patient). Grade 3 or 4 adverse events occurred in five (11%) patients receiving eltrombopag and four (19%) patients receiving placebo, and serious adverse events (four 9% patients receiving eltrombopag and two (10%) patients receiving placebo) were similarly infrequent in both groups. No thrombotic events or malignancies occurred. Increased alanine aminotransferase concentrations caused two (3%) of 65 patients to discontinue eltrombopag in the open-label phase.
Our results showed that eltrombopag could be used to increase platelet counts and reduce clinically significant bleeding in children with persistent or chronic immune thrombocytopenia. Prevalence of increased liver laboratory values was similar to that seen in adults.
GlaxoSmithKline.
Objective
Post‐traumatic epilepsy (PTE) is an acquired epilepsy that develops in the months or years following a traumatic brain injury (TBI) and can lead to substantial personal, financial, and ...societal burden. To date, PTE is rarely curable; current treatments are partially effective and often accompanied by adverse side effects. While research on PTE has expanded significantly in the last several years, there remain numerous challenges to identifying effective prevention and treatment strategies. In this paper, we describe advances from the CURE Epilepsy PTE Initiative, including its implementation and the emphasis on team science.
Methods
The CURE Epilepsy PTE Initiative funded six research teams to link preclinical and clinical studies to engage in the validation of experimental models, characterization of pathophysiology and biological pathways, and identification of risk factors associated with PTE. Three teams had projects with both a preclinical and a clinical component; these teams focused on: targeting the epileptogenic effects of subarachnoid blood, exploring the neuropathological mechanisms of epileptogenesis, and defining the role of extracellular matrix injury. Two teams undertook entirely preclinical projects: exploring the role of vascular injury, gliosis, and neurogenesis as drivers for PTE, and identifying genetic, proteomic, metabolomic, and microRNA biosignatures to improve the prediction of PTE. One team's project was entirely clinical and investigated genetic and protein biomarkers to improve the prediction of PTE.
Results
In addition to scientific discoveries including characterization of a variety of animal models and progress towards the understanding of biological underpinnings and biomarkers for PTE, significant programmatic and personnel‐related processes were incorporated, including standardized, rigorous policies and procedures to ensure quality and accountability between and within groups.
Significance
We propose CURE Epilepsy's team science approach as an effective way to bring together a diverse set of investigators to explore biological mechanisms that may lead to cures for the epilepsies.
Biological systems present remarkable adaptation, reliability, and robustness in various environments, even under hostility. Most of them are controlled by the individuals in a distributed and ...self-organized way. These biological mechanisms provide useful resources for designing the dynamical and adaptive routing schemes of wireless mobile sensor networks, in which the individual nodes should ideally operate without central control. This paper investigates crucial biologically inspired mechanisms and the associated techniques for resolving routing in wireless sensor networks, including Ant-based and genetic approaches. Furthermore, the principal contributions of this paper are as follows. We present a mathematical theory of the biological computations in the context of sensor networks; we further present a generalized routing framework in sensor networks by diffusing different modes of biological computations using Ant-based and genetic approaches; finally, an overview of several emerging research directions are addressed within the new biologically computational framework.
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