Comparison of neuroimaging by CT and MRI and correlation with neurological presentation in eclampsia

Background: The objective of the study was to compare computed tomography (CT) and magnetic resonance imaging (MRI) findings of eclampsia patients with respect to neurological signs and symptoms.Methods: This is a prospective observational study, 25 patients of eclampsia were studied, statistical analysis was done by Fishers’ exact and chi square test.Results: All patients in our study presented with antepartum or intrapartum eclampsia with neurological features ranging from headache, altered consciousness to coma. On neuroimaging by MR transiently high T2 signal intensity in the cerebral cortex and sub cortical white matter was seen, including edema. With MR angiography generalized vasospasm was also seen in 40% cases. MRI was found to be co-relating more than CT with the neurological presentation and had 90% sensitivity and 100% sensitivity.Conclusions: Symptoms like visual blurring, loss of vision and ophthalmological signs in eclampsia suggest occipital lobe involvement. Magnetic resonance imaging abnormalities in eclampsia correlate well with clinical findings as compared to CT and can be better imaging modality in eclampsia patients

Supply chains and antitrust governance

Antitrust regulations are meant to promote fair competition in the market, but balancing administrative and legal costs with enforcement can be difficult when multilayered supply chains are involved. The canonical example of this challenge is the landmark Illinois Brick ruling, which limits antitrust damages to only the direct purchasers of a product; for instance, consumers can file antitrust claims against colluding retailers but not against colluding manufacturers—only retailers can file claims against manufacturers. This controversial ruling was meant to reduce legal costs, but it can clearly lead to missed enforcement opportunities. In this paper, we demonstrate how the Illinois Brick ruling interacts with contracts adopted in the supply chain, and we show that otherwise equivalent supply chain arrangements can have markedly different effects. In particular, we find that wholesale price, minimum order quantity, revenue sharing, and quantity discount contracts lead retailers to take legal action against manufacturers in the event of collusive behavior. However, the wholesale price plus fixed fee contract structure (also known as a two-part tariff or slotting fee contract) facilitates collusion among the manufacturers with retailers compensated by the fixed fee and not filing the antitrust litigation. We further demonstrate that collusion is more likely under high demand uncertainty and high competition at the retail level but is less likely under high competition at the manufacturer level. Our paper helps public enforcers identify market conditions conducive to antitrust violations

Global text mining and development of pharmacogenomic knowledge resource for precision medicine

Understanding patients' genomic variations and their effect in protecting or predisposing them to drug response phenotypes is important for providing personalized healthcare. Several studies have manually curated such genotype-phenotype relationships into organized databases from clinical trial data or published literature. However, there are no text mining tools available to extract high-accuracy information from such existing knowledge. In this work, we used a semiautomated text mining approach to retrieve a complete pharmacogenomic (PGx) resource integrating disease-drug-gene-polymorphism relationships to derive a global perspective for ease in therapeutic approaches. We used an R package, pubmed.mineR, to automatically retrieve PGx-related literature. We identified 1,753 disease types, and 666 drugs, associated with 4,132 genes and 33,942 polymorphisms collated from 180,088 publications. With further manual curation, we obtained a total of 2,304 PGx relationships. We evaluated our approach by performance (precision = 0.806) with benchmark datasets like Pharmacogenomic Knowledgebase (PharmGKB) (0.904), Online Mendelian Inheritance in Man (OMIM) (0.600), and The Comparative Toxicogenomics Database (CTD) (0.729). We validated our study by comparing our results with 362 commercially used the US- Food and drug administration (FDA)-approved drug labeling biomarkers. Of the 2,304 PGx relationships identified, 127 belonged to the FDA list of 362 approved pharmacogenomic markers, indicating that our semiautomated text mining approach may reveal significant PGx information with markers for drug response prediction. In addition, it is a scalable and state-of-art approach in curation for PGx clinical utility

Genetic landscape of common epilepsies: advancing towards precision in treatment

Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood absence epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy and epilepsy with generalized tonic-clonic seizure on awakening and focal epilepsy like temporal lobe epilepsy and cryptogenic focal epilepsy. In 70% of the epilepsy cases, genetic factors are responsible either as single genetic variant in rare epilepsies or multiple genetic variants acting along with different environmental factors as in common epilepsies. Genetic testing and precision treatment have been developed for a few rare epilepsies and is lacking for common epilepsies due to their complex nature of inheritance. Precision medicine for common epilepsies require a panoramic approach that incorporates polygenic background and other non-genetic factors like microbiome, diet, age at disease onset, optimal time for treatment and other lifestyle factors which influence seizure threshold. This review aims to comprehensively present a state-of-art review of all the genes and their genetic variants that are associated with all common epilepsy subtypes. It also encompasses the basis of these genes in the epileptogenesis. Here, we discussed the current status of the common epilepsy genetics and address the clinical application so far on evidence-based markers in prognosis, diagnosis, and treatment management. In addition, we assessed the diagnostic predictability of a few genetic markers used for disease risk prediction in individuals. A combination of deeper endo-phenotyping including pharmaco-response data, electro-clinical imaging, and other clinical measurements along with genetics may be used to diagnose common epilepsies and this marks a step ahead in precision medicine in common epilepsies management

Summary for Policymakers

The Working Group III (WGIII) contribution to the IPCC’s Sixth Assessment Report (AR6) assesses literature on the scientific, technological, environmental, economic and social aspects of mitigation of climate change.The report reflects new findings in the relevant literature and builds on previous IPCC reports, including the WGIII contribution to the IPCC’s Fifth Assessment Report (AR5), the WGI and WGII contributions to AR6 and the three Special Reports in the Sixth Assessment cycle, as well as other UN assessments

The effectiveness of a multidisciplinary intervention strategy for the treatment of symptomatic joint hypermobility in childhood:A randomised, single Centre parallel group trial (The Bendy Study)

Introduction: Joint hypermobility is common in childhood and can be associated with musculoskeletal pain and dysfunction. Current management is delivered by a multidisciplinary team, but evidence of effectiveness is limited. This clinical trial aimed to determine whether a structured multidisciplinary, multisite intervention resulted in improved clinical outcomes compared with standard care. Method: A prospective randomised, single centre parallel group trial comparing an 8-week individualised multidisciplinary intervention programme (bespoke physiotherapy and occupational therapy in the clinical, home and school environment) with current standard management (advice, information and therapy referral if deemed necessary). The primary endpoint of the study was between group difference in child reported pain from baseline to 12 months as assessed using the Wong Baker faces pain scale. Secondary endpoints were parent reported pain (100 mm visual analogue scale), parent reported function (child health assessment questionnaire), child reported quality of life (child health utility 9-dimensional assessment), coordination (movement assessment battery for children version 2) and grip strength (handheld dynamometer). Results: 119 children aged 5 to 16 years, with symptomatic hypermobility were randomised to receive an individualised multidisciplinary intervention (I) (n = 59) or standard management (S) (n = 60). Of these, 105 completed follow up at 12 months. No additional significant benefit could be shown from the intervention compared to standard management. However, there was a statistically significant improvement in child and parent reported pain, coordination and grip strength in both groups. The response was independent of the degree of hypermobility. Conclusion: This is the first randomised controlled trial to compare a structured multidisciplinary, multisite intervention with standard care in symptomatic childhood hypermobility. For the majority, the provision of education and positive interventions aimed at promoting healthy exercise and self-management was associated with significant benefit without the need for more complex interventions. Trial registration: The trial was registered prospectively with the national database at the Clinical Research Network (UKCRN Portfolio 9366). The trial was registered retrospectively with ISRCTN (ISRCTN86573140)

Tumor macroenvironment and metabolism

In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%–20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient’s outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described