A Review on Grid Integration Challenges of Wind Energy Systems

In recent decades, the strengthening of electric energy security and the reduction of greenhouse gas emissions acquired great traction. The integration of large-scale intermittent renewable energy resources (RER) such as wind energy into existing electrical systems has risen dramatically in recent years. In the last few years, however, this integration creates several operational and control issues that impede the process. Grid functioning must be reliable and stable. This article will look at the problems that have been documented as a result of the recommended solutions techniques and the integration of wind energy Among the many difficulties, Generation uncertainty, power quality difficulties, angular and voltage stability, and reactive power support are all factors to consider. The ability to ride through faults is examined and explored. Aside from that, there are financial, environmental, and political factors to consider

A comparative clinical study to evaluate the effect of Indrayavadi Yoga and Bhoomyamalaki Choorna in the management of Asrigdara w.s.r. to Puberty Menorrhagia

A normal menstruation denotes a healthy state of female reproductive system. If the menstrual bleeding is abnormally excessive, prolonged and is associated with pain, it indicates some pathology. The abnormal menstrual cycle not only disturbs the general health, it also disturbs routine work schedule of the woman and her entire family. There is no direct reference of Puberty menorrhagia in classics. Puberty menorrhagia is defined as excessive bleeding occurring between menarche to 19 years of age. Anovulatory bleeding with irregular shedding of endometrium is the cause for puberty Menorrhagia which can be effectively tackled with the help of herbal drugs which contains hemostatic action. Asrigdara mainly due to vitiation of Vata and Pitta Doshas, hence the treatment should be based on use of drugs which are having predominance of Kashayarasa and Pitta-Vatashamaka properties and Stambhan action. Thus selected drugs are Indrayavadi Yoga and Bhoomyamalaki Choorna possess Vata-Pitta Shamaka and Raktastambhaka. This research work is comparative clinical study. 40 patients presenting with Pratyatma Lakshana of Asrigdara were randomly selected and divided into 2 groups of 20 patients each. Group A were given Indrayavadi Yoga and group B were given Bhoomyamalaki Choorna for a period of 2 menstrual cycle and two follow up during treatment and one follow up after treatment. After the completion of clinical trial, it was found that Bhoomyamalaki Choorna which was group B is more effective than group A. The overall effect in group A and Group B, both the groups shown excellent response, but when comparing all the parameters Bhoomyamalaki Choorna shown more significant response than Indrayavadi Yoga. Trial drug is a better remedy for Asrigdara. It has no side effect, cost effective

IONTOPHORETIC DRUG DELIVERY: A NOVEL APPROACH THROUGH TRANSDERMAL ROUTE

ABSTRACT The goal of delivery system is to get optimal therapeutic management. But, it still remains a challenge in the field of pharmaceuticals for delivery of ionic species and some non ionic. Several transdermal approaches have been used and recently the Iontophoretic technique has been widely used. This technique of facilitated movement of ion across a membrane under the influence of an externally applied potential difference is one of the most promising physical penetrations enhancing method. The rationale behind using this technique is the capability of this method to increase the systemic delivery of high molecular weight compounds with controlled input kinetics. Also improved systemic bioavailability, ensuring from bypassing the first pass metabolism. This article presents a review of literature relating to iontophoresis. This review briefly describes the history of iontophoresis and discussion of factors which affect Iontophoretic drug delivery. Present review also provides its applications for various clinical conditions

Research Article A New Informatics Framework for Evaluating the Codon Usage Metrics, Evolutionary Models and Phylogeographic Reconstruction of Tomato Yellow Leaf Curl Virus (TYLCV) in Different Regions of Asian Countries

Not AvailableTomato yellow leaf curl virus (TYLCV) is a major devastating viral disease, majorly affecting the tomato production globally. The disease is majorly transmitted by the Whitefly. The Begomovirus (TYLCV) having a six major protein coding genes, among them the C1/AC1 is evidently associated with viral replication. Owing to immense role of C1/AC1 gene, the present study is an initial effort to elucidate the factors shaping the codon usage bias and evolutionary pattern of TYLCV-C1/AC1 gene in five major Asian countries. Based on publicly available nucleotide sequence data the Codon usage pattern, Evolutionary and Phylogeographic reconstruction was carried out. The study revealed the presence of significant variation between the codon bias indices in all the selected regions. Implying that the codon usage pattern indices (eNC, CAI, RCDI, GRAVY, Aromo) are seriously affected by selection and mutational pressure, taking a supremacy in shaping the codon usage bias of viral gene. Further, the tMRCA age was 1853, 1939, 1855, 1944, 1828 for China, India, Iran, Oman and South Korea, respectively for TYLCV-C1/AC1 gene. The integrated analysis of Codon usage bias, Evolutionary rate and Phylogeography analysis in viruses signifies the positive role of selection and mutational pressure among the selected regions for TYLCV (C1/AC1) gene.Not Availabl

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A unique case of bifid left testicular artery having its anomalous high origin from renal artery

The testicular arteries are known to originate from the ventrolateral aspect of the abdominal aorta and descend obliquely to the pelvic cavity and supply the testis. An anatomical description of an uncommon variation of the left testicular artery is presented in this case report, highlighting its clinical implications. During routine dissection of a male cadaver, we found that the left testicular artery was bifid and it was arising from the left renal artery. After its origin, it then coursed behind the left renal vein, passed between the left testicular vein and left ureter and at the lower pole of the left kidney, this bifid testicular artery joined to form a single testicular artery which thereafter presented a normal course. Anatomy of the testicular artery has been studied in detail because of its importance in testicular physiology, as well as its significance in testicular and renal surgery. This vascular variation shows a major significance in renal surgery, partial or total nephrectomy, and renal transplant. In addition, this anatomical variation enhances the importance of arteriography or the Doppler ultrasound examination of the renal hilum before surgeries

CD34 positive-microgranular variant of acute promyelocytic leukemia in a child

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) in which abnormal promyelocytes predominate. APL is rare in children (approximately 10% of childhood AML) and is characterized by a higher incidence of hyperleukocytosis, an increased incidence of microgranular morphology, the presence of balanced t(15;17)(q22;q11.2-12) translocation, and more frequent occurrence of the PML-RARα isoforms bcr 2 and bcr 3 compared to adults. The cytomorphology of microgranular variant blasts is obviously different from AML M3 blasts; these cells have a nongranular or hypogranular cytoplasm or contain fine dust-like cytoplasmic azurophil granules that may not be apparent by light microscopy. This case report emphasizes the importance of a high index of suspicion for the diagnosis of APL, the hypogranular variant in particular. They are responsive to differentiation therapy with all trans-retinoic acid and complete remission in seen in >80% cases