Chronic inflammation is an aberrantly prolonged form of a protective response to a loss of tissue homeostasis and it is involved in several steps of the carcinogenesis process. As a result, many ...cancers are inflammation-related. The systemic inflammatory response is associated with survival in advanced and localized cancers. Two categories of scores have been proposed to monitor the systemic inflammatory response, those derived from protein measurement and those based on counting inflammatory cells. This review aims to provide a critical appraisal of these 2 categories of surrogate markers. The 3 scale modified Glasgow prognostic score (mGPS) is based on the combination of C-reactive protein and albumin and is graded 0 to 2. It has been validated worldwide showing an independent prognostic value in patients with cancer in a variety of tumour types and tumour stages. Leukocytes-based scores are mainly neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Elevated NLR and/or PLR and lower LMR seem to be associated with decreased survival, but the studies about these markers are very heterogeneous. The main limit is the variety of thresholds used to dichotomize patients, so that reproducibility and reliability of leukocytes-based scores can be questioned. Hence, there is no sufficient evidence to support their use in clinical practice. Comprehensive management of patients with operable and advanced cancer should integrate the host systemic inflammatory response by calculating the mGPS. It could be a helpful tool to tailor patients' management.
Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with ...5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.
This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m2 twice daily on days 1–14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13.
Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37–60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6–59·1) in the capecitabine group compared with 36·4 months (29·7–44·5) in the observation group (adjusted hazard ratio HR 0·81, 95% CI 0·63–1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55–0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30–44) in the observation group (adjusted HR 0·75, 95% CI 0·58–0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6–35·9) in the capecitabine group and 17·5 months (12·0–23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8–46·3) in the capecitabine group and 17·4 months (12·0–23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (<1%) patient had grade 4 cardiac ischaemia or infarction. Serious adverse events were observed in 47 (21%) of 223 patients in the capecitabine group and 22 (10%) of 224 patients in the observation group. No deaths were deemed to be treatment related.
Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.
Cancer Research UK and Roche.
Narrowband internet of things (NB-IoT) is a recent cellular radio access technology based on Long-Term Evolution (LTE) introduced by Third-Generation Partnership Project (3GPP) for Low-Power ...Wide-Area Networks (LPWAN). The main aim of NB-IoT is to support massive machine-type communication (mMTC) and enable low-power, low-cost, and low-data-rate communication. NB-IoT is based on LTE design with some changes to meet the mMTC requirements. For example, in the physical (PHY) layer only single-antenna and low-order modulations are supported, and in the Medium Access Control (MAC) layers only one physical resource block is allocated for resource scheduling. The aim of this survey is to provide a comprehensive overview of the design changes brought in the NB-IoT standardization along with the detailed research developments from the perspectives of Physical and MAC layers.
Securing communications in vehicle ad hoc networks is crucial for operations. Messages exchanged in vehicle ad hoc network communications hold critical information such as road safety information, or ...road accident information and it is essential these packets reach their intended destination without any modification. A significant concern for vehicle ad hoc network communications is that malicious vehicles can intercept or modify messages before reaching their intended destination. This can hamper vehicle ad hoc network operations and create safety concerns. The multi-tier trust management system proposed in this paper addresses the concern of malicious vehicles in the vehicle ad hoc network using three security tiers. The first tier of the proposed system assigns vehicles in the vehicle ad hoc network a trust value based on behaviour such as processing delay, packet loss and prior vehicle behavioural history. This will be done by selecting vehicles as watchdogs to observe the behaviour of neighbouring vehicles and evaluate the trust value. The second tier is to protect the watchdogs, which is done by watchdogs’ behaviour history. The third security tier is to protect the integrity of data used for trust value calculation. Results show that the proposed system is successful in identifying malicious vehicles in the VANET. It also improves the packet delivery ratio and end-to-end delay of the vehicle ad hoc network in the presence of malicious vehicles.
Activating mutations in KRAS have been suggested as potential predictive and prognostic biomarkers. However, the prognostic impact of specific point mutations remains less clear. This study assessed ...the prognostic impact of specific KRAS mutations on survival for patients with colorectal cancer.
Retrospective review of patients KRAS typed for advanced and recurrent colorectal cancer between 2010 and 2015 in a UK Cancer Network.
We evaluated the impact of KRAS genotype in 392 patients. Mutated KRAS was detected in 42.9% of tumours. KRAS mutations were more common in moderate vs well-differentiated tumours. On multivariate analysis, primary tumour T stage (HR 2.77 (1.54-4.98), P=0.001), N stage (HR 1.51 (1.01-2.26), P=0.04), curative intent surgery (HR 0.51 (0.34-0.76), P=0.001), tumour grade (HR 0.44 (0.30-0.65), P=0.001) and KRAS mutation (1.54 (1.23-2.12), P=0.005) were all predictive of overall survival. Patients with KRAS codon 12 mutations had worse overall survival (HR 1.76 (95% CI 1.27-2.43), P=0.001). Among the five most common codon 12 mutations, only p.G12C (HR 2.21 (1.15-4.25), P=0.01) and p.G12V (HR 1.69 (1.08-2.62), P=0.02) were predictive of overall survival.
For patients with colorectal cancer, p.G12C and p.G12V mutations in codon 12 were independently associated with worse overall survival after diagnosis.
The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the ...long-term data and novel exploratory subgroup analyses.
This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m
twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13.
Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex.
This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.
Single-point incremental forming (SPIF) of polymers was started back in the first decade of twenty-first century; since then, substantial studies have been performed on this topic. The present ...article reviews these studies and compiles the developments in a comprehensive manner. The review entails a number of forming aspects of polymers, the more important of which are deformation mechanics, failure modes, formability, forming forces, springback, and post-forming material characteristics. The agreements and disagreements amongst the researchers are recognized and critical remarks are provided. The issues are identified, and areas of future work are proposed to further comprehend knowledge on the subject in order to successfully deploy the process on industrial scale. The differences in the characteristics of SPIF of polymers and SPIF of metals are also outlined and discussed in this article. The review concludes that the operating parameters and material are the key factors that affect the process performance. Further, the innovative technology must be adopted, and a larger database should be established to enhance industrial viability of the process.
Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia ...associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long‐term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia‐associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs.
Thematic of bromocriptine’s therapy mechanism of actions
Nowadays, Free Space Optical (FSO) communication has attained great importance because of high features such as large data rate, low power, and huge bandwidth. However, FSO technology suffers from ...several atmospheric effects such as rain, snow, fog, etc. To overcome these issues, an innovative Selective Active Relay (SAR) protocol is proposed in this research. Here, the SAR method is utilized for selecting the relays in FSO, which is used for better communication without any difficulties like atmospheric conditions. Also, a novel Water Pouring Erbium-Doped Fiber Amplifier (WPEDFA) method is introduced to allocate the power for relays and calculates the outage probability. Moreover, the current research introduces an innovative Optimum Enhanced African Buffalo (OE-AB) algorithm to optimize the error and outage probability. Eventually, the proposed approach analyzes the Bit Error Rate (BER) and Quality factor (Q-factor) under atmospheric conditions. Also, the proposed WPEDFA approach is utilized for allocating power to the relays. Moreover, the OE-AB algorithm optimizes the error rate and outage probability. Also, the simulation of this model is done by MATLAB, and attained results prove the effectiveness of the proposed approach. Consequently, it achieves a lower BER and outage probability compared with other techniques.
The vision of the Internet of Things (IoT) is to enable systems across the globe to share data using advanced communication technologies. With the recent technological advancements, IoT-based ...solutions are no longer a challenging vision. IoT will offer numerous and potentially revolutionary benefits to today's digital world. Future personalized and connected healthcare is one of the promising areas to see the benefits of IoT. This paper surveys emerging healthcare applications, including detailed technical aspects required for the realization of a complete end-to-end solution for each application. The survey explores the key application-specific requirements from the perspective of communication technologies. Furthermore, a detailed exploration from the existing to the emerging technologies and standards that would enable such applications is presented, highlighting the critical consideration of short-range and long-range communications. Finally, the survey highlights important open research challenges and issues specifically related to IoT-based future healthcare systems.
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