Use of magnetic fluids in process system for pipe isolations.

This paper investigates the use of magnetic fluids known as ferrofluids to act as valves within pipe systems to create isolation points for stemming pipe leakages and to halt leakages before they become largescale disasters. The sealing abilities of ferrofluids were proven for microvalves (ID ≤ 1 mm) in hydrostatic experiments and extended to the macroscale applications (ID ≥ 6 mm). Theoretical prediction and magnetic finite element analysis (FEA) were also undertaken to predict the burst pressure, and a comparison of both results against the experimental measurement was made.

Differential effect of an evolving amyloid and tau pathology on brain phospholipids and bioactive lipid mediators in rat models of Alzheimer-like pathology.

Background: Brain inflammation contributes significantly to the pathophysiology of Alzheimer's disease, and it is manifested by glial cell activation, increased production of cytokines/chemokines, and a shift in lipid mediators from a pro-homeostatic to a pro-inflammatory profile. However, whether the production of bioactive lipid mediators is affected at earlier stages, prior to the deposition of Aβ plaques and tau hyperphosphorylation, is unknown. The differential contribution of an evolving amyloid and tau pathology on the composition and abundance of membrane phospholipids and bioactive lipid mediators also remains unresolved.

Stroma AReactive Invasion Front Areas (SARIFA) improves prognostic risk stratification of perioperative chemotherapy treated oesophagogastric cancer patients from the MAGIC and the ST03 trial.

Background: Tumour-associated fat cells without desmoplastic stroma reaction at the invasion front (Stroma AReactive Invasion Front Areas (SARIFA)) is a prognostic biomarker in gastric and colon cancer. The clinical utility of the SARIFA status in oesophagogastric cancer patients treated with perioperative chemotherapy is currently unknown.

Methods: The SARIFA status was determined in tissue sections from patients recruited into the MAGIC (n = 292) or ST03 (n = 693) trials treated with surgery alone (S, MAGIC) or perioperative chemotherapy (MAGIC, ST03).

Neuronal loss and inflammation preceding fibrillary tau pathology in a rat model with early human-like tauopathy.

In tauopathies such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), the microtubule associated protein tau undergoes conformational and posttranslational modifications in a gradual, staged pathological process. While brain atrophy and cognitive decline are well-established in the advanced stages of tauopathy, it is unclear how the early pathological processes manifest prior to extensive neurodegeneration. For these studies we have applied a transgenic rat model of human-like tauopathy in its heterozygous form, named McGill-R955-hTau.

Progressive human-like tauopathy with downstream neurodegeneration and neurovascular compromise in a transgenic rat model.

Tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD), clinically present with progressive cognitive decline and the deposition of neurofibrillary tangles (NFTs) in the brain. Neurovascular compromise is also prevalent in AD and FTD however the relationship between tau and the neurovascular unit is less understood relative to other degenerative phenotypes. Current animal models confer the ability to recapitulate aspects of the CNS tauopathies, however, existing models either display overaggressive phenotypes, or do not develop neuronal loss or genuine neurofibrillary lesions.

Obinutuzumab as consolidation after chemo-immunotherapy: Results of the UK National Cancer Research Institute phase II/III GALACTIC trial.

The GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In chronic lymphocytic leukaemia (CLL) (GALACTIC) was a seamless phase II/III trial designed to test whether consolidation with obinutuzumab is safe and eradicates minimal residual disease (MRD) and, subsequently, whether this leads to prolonged progression-free survival (PFS) in patients with CLL who have recently responded to chemo-immunotherapy. Patients with a response 3-24 months after chemotherapy were assessed for MRD. MRD-positive patients were randomised to receive consolidation therapy with obinutuzumab or no consolidation.

Neoadjuvant chemotherapy improves survival in patients with oesophageal mucinous adenocarcinoma: Post-hoc analysis of the UK MRC OE02 and OE05 trials.

Background: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeAC) do not benefit from neoadjuvant chemotherapy.

Absence of DEATH kinesin is fatal for Leishmania mexicana amastigotes.

Kinesins are motor proteins present in organisms from protists to mammals playing important roles in cell division, intracellular organisation and flagellum formation and maintenance. Leishmania mexicana is a protozoan parasite of the order Kinetoplastida causing human cutaneous leishmaniasis. Kinetoplastida genome sequence analyses revealed a large number of kinesins showing sequence and structure homology to eukaryotic kinesins.

Prognostic Significance of Negative Lymph Node Long Axis in Esophageal Cancer: Results From the Randomized Controlled UK MRC OE02 Trial.

Objective: To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients.

Background: Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC.

Long-term patient-reported outcomes in men with Peyronie's disease undergoing nonsurgical and nonintralesional injection management.

Peyronie's disease (PD) has a negative impact on overall quality of life for many patients and their partners. There is a significant portion of patients who elect noninvasive therapy and in this scenario we have little data with which to counsel patients. We aim to evaluate long-term patient-reported outcomes in a cohort of men with PD who elected conservative treatment.

NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats.

Epidemiological, preclinical, and clinical studies have suggested a role for microdose lithium in reducing Alzheimer's disease (AD) risk by modulating key mechanisms associated with AD pathology. The novel microdose lithium formulation, NP03, has disease-modifying effects in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis at pre-plaque stages, before frank amyloid-β (Aβ) plaque deposition, during which Aβ is primarily intraneuronal. Here, we are interested in determining whether the positive effects of microdose lithium extend into early Aβ post-plaque stages.

Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-carbon Metabolism.

Paraquat is an herbicide that is commonly used worldwide. Exposure to paraquat results in Parkinson's disease (PD)-like symptoms including dopaminergic cell loss. Nutrition has also been linked in the pathogenesis of PD, such as reduced levels of folic acid, a B-vitamin, and component of one-carbon metabolism.

Physician-patient communication at prescription of an additional oral drug for type 2 diabetes and its links to patient outcomes - New findings from the global IntroDia® study.

Aims: To investigate experiences of people with type 2 diabetes (T2DM) at the clinic visit when an additional oral antidiabetes drug (OAD) is prescribed, and how this affects their quality of life, self-management and key outcomes.

Methods: We surveyed adults with T2DM from a large multinational study of patient-physician communication during early T2DM treatment (IntroDia®). We examined their experiences when an additional OAD is prescribed ("add-on") after initial OAD monotherapy, focusing on 24 key conversational elements, overall patient-perceived communication quality (PPCQ), and associations with current patient-reported outcomes.

Physician experiences when discussing the need for additional oral medication with type 2 diabetes patients: Insights from the cross-national IntroDia® study.

Aims: Physician-patient communication when discussing the need for additional oral medication for type 2 diabetes (add-on) may affect the self-care of people with this condition. We aimed to investigate physicians' recalled experiences of the add-on consultation.

Methods: We conducted a cross-sectional survey of physicians treating people with type 2 diabetes in 26 countries, as part of a large cross-national study of physician-patient communication during early treatment of type 2 diabetes (IntroDia®).

A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke.

Stroke is a leading cause of disability and death world-wide and nutrition is a modifiable risk factor for stroke. Metheylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of folic acid, a B-vitamin. In humans, a polymorphism in MTHFR (677C→T) is linked to increased risk of stroke, but the mechanisms remain unknown.

B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke.

Folates are B-vitamins that play an important role in brain function. Dietary and genetic deficiencies in folate metabolism result in elevated levels of homocysteine which have been linked to increased risk of developing a stroke. Reducing levels of homocysteine before or after a stroke through B-vitamin supplementation has been a focus of many clinical studies, however, the results remain inconsistent.

A genetic study of Wilson's disease in the United Kingdom.

Previous studies have failed to identify mutations in the Wilson's disease gene ATP7B in a significant number of clinically diagnosed cases. This has led to concerns about genetic heterogeneity for this condition but also suggested the presence of unusual mutational mechanisms. We now present our findings in 181 patients from the United Kingdom with clinically and biochemically confirmed Wilson's disease.

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

Background: Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I-III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance.

Idiopathic cytopenia of undetermined significance and the minimal criteria for a diagnosis of myelodysplastic syndrome.

A bone marrow examination in a young woman with anemia and β-thalassemia trait showed dyserythropoiesis in less than 10% of erythroblasts without other myelodysplastic changes, and cytogenetic analysis revealed trisomy of chromosome 8. Although she did not fulfill the current World Health Organization (WHO) criteria for diagnosis of a myelodysplastic syndrome, her acquired bone marrow disorder behaved as such, and she later developed acute myeloid leukemia.