Development of a deep learning method to identify acute ischaemic stroke lesions on brain CT.

Background: CT is commonly used to image patients with ischaemic stroke but radiologist interpretation may be delayed. Machine learning techniques can provide rapid automated CT assessment but are usually developed from annotated images which necessarily limits the size and representation of development data sets. We aimed to develop a deep learning (DL) method using CT brain scans that were labelled but not annotated for the presence of ischaemic lesions.

The MARECA (national study of management of breast cancer locoregional recurrence and oncological outcomes) study: protocol for a prospective, multicentre cohort study.

Background: Despite a UK 5-year breast cancer survival rate of 86.6%, patients may develop breast cancer recurrence within the same breast after breast conserving surgery, as well as in the remaining skin or chest wall after mastectomy or in the ipsilateral lymph glands. These recurrences, collectively termed locoregional recurrence (LRR), occur in around 8% of patients within 10 years of their original diagnosis.

Breaking Barriers With Basal Insulin Biosimilars in Type 2 Diabetes.

Despite increases in the availability and effectiveness of other therapies, insulin remains an essential treatment for approximately 30 million people with type 2 diabetes worldwide. The development of biosimilars has created the potential for significant health care cost savings and may lead to greater access to basal insulin for vast populations. In this review, we discuss evidence demonstrating equipoise between basal insulin biosimilars and the patented analogs they may replace.

Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: pooled 52-week outcomes from the DEPICT-1 and -2 studies.

Aim: To evaluate the efficacy and safety of adjunct dapagliflozin therapy in patients with type 1 diabetes (T1D).

Materials And Methods: DEPICT-1 and -2 were randomized, double-blind, parallel-group, 24-week studies, with 28-week extension periods. Adults with T1D and HbA1c 7.

Systematic review and meta-analysis of randomized controlled trials of psychological interventions to improve glycaemic control in children and adults with type 1 diabetes.

Aim: We conducted a systematic review aggregate and network meta-analysis of psychological interventions for people with type 1 diabetes to assess their effectiveness in improving glycaemic levels.

Methods: We searched the following databases from 1 January 2003 to 1 July 2018: MEDLINE, CINAHL, PsycINFO, Embase, Cochrane Controlled Trials, Web of Science, clinicaltrials.gov, Dissertation Abstract International.

Sexually transmitted infections and travel.

Purpose Of Review: The present review considers recent evidence on travel-associated sexual intercourse and sexually transmitted infection (STI) risks and travel with regards to risk behavior and implications of travel on communities. It highlights the lack of research in this area and topics for consideration.

Recent Findings: A population-based study, and others, shows significant levels of sex abroad and risk behavior with inconsistent condom use despite increasing travel advice about risks.

Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells.

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway.

Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma.

Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing luminescent mouse fibrosarcomas expressing single VEGFA isoforms or their wild-type counterparts expressing all isoforms (fs120, fs164, fs188, or fsWT). Expression of the more soluble isoforms conferred an advantage for lung metastasis from subcutaneous tumors (fs120/164 vs.

Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure.

The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem-also called "microbiome"-is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections.

An evaluation of factors influencing the assessment time in a nurse practitioner-led anaesthetic pre-operative assessment clinic.

Elective patients undergoing anaesthetic pre-operative assessment are usually allocated the same period of time with a nurse practitioner, leading to potential inefficiencies in patient flow through the clinic. We prospectively collected data on 8519 patients attending a pre-operative assessment clinic. The data set were split into derivation and validation cohorts.

Sexually transmitted infections in children as a marker of child sexual abuse and direction of future research.

Purpose Of Review: This review considers recent evidence on sexually transmitted infections (STIs) as a marker of child sexual abuse (CSA), when diagnosed after the neonatal period. It also aims to identify if there are specific areas where additional research is required.

Recent Findings: An evidence-based systematic review using strict inclusion criteria shows that CSA is a major cause of STIs in children.

Student assistantships: bridging the gap between student and doctor.

In 2009, the General Medical Council UK (GMC) published its updated guidance on medical education for the UK medical schools - Tomorrow's Doctors 2009. The Council recommended that the UK medical schools introduce, for the first time, a clinical placement in which a senior medical student, "assisting a junior doctor and under supervision, undertakes most of the duties of an F1 doctor". In the UK, an F1 doctor is a postgraduation year 1 (PGY1) doctor.

Inhaled nitric oxide in acute pulmonary embolism: a systematic review.

Acute pulmonary embolism (PE) is usually a complication secondary to migration of a deep venous clot or thrombi to lungs, but other significant etiologies include air, amniotic fluid, fat, and bone marrow. Regardless of the underlying etiology, little progress has been made in finding an effective pharmacologic intervention for this serious complication. Among the wide spectrum of PE, massive PE is associated with considerable morbidity and mortality, primarily due to severely elevated pulmonary vascular resistance leading to right ventricular failure, hypoxemia, and cardiogenic shock.

Ebola virus as a sexually transmitted infection.

Purpose Of Review: The ongoing Ebola virus epidemic in West Africa is a major global health challenge. The main mode of transmission is through contact with bodily fluids and skin of those infected or who have died. This review was undertaken to consider the evidence for transmission by contact with bodily fluids occurring through sexual activity.

Inhibitors of cell cycle checkpoints and DNA replication cause different responses in normal versus malignant urothelial cells.

S-phase checkpoints are triggered in tumor cells in response to DNA replication stress caused by the tumor microenvironment or oncogenes. A recent report from our laboratory showed that tumor cells and more normal epithelial cells have a very different response to replication stress. In this Author's View, the implications of this finding are discussed.

Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors.

While DNA damage response pathways are well characterized in cancer cells, much less is known about their status in normal cells. These pathways protect tumour cells from DNA damage and replication stress and consequently present potential therapeutic targets. Here we characterize the response of human telomerase reverse transcriptase (hTERT)-immortalized normal human urothelial (NHU) and bladder cancer cell lines to agents that disrupt the DNA damage response.

Long-range DNA interactions at the IL-1/IL-36/IL-37 gene cluster (2q13) are induced by activation of monocytes.

The interleukin-1 gene cluster occupies a 360kb region of chromosome 2q13 and contains nine homologous genes. These include agonists and antagonists of the parallel IL-1 and IL-36 systems, and IL1F7, the gene encoding IL-37. As the genes of the cluster are structurally and functionally related and have similar mRNA kinetics, we have sought evidence for gene induction-specific looping of chromatin in the IL-1 cluster by chromatin conformation capture (3C).

A method for the in vivo measurement of zebrafish tissue neutrophil lifespan.

Neutrophil function is thought to be regulated, in large part, by limitation of lifespan by apoptosis. A number of studies suggest that circulating neutrophils have a half-life of approximately 6 hours, although contradictory evidence exists. Measuring tissue neutrophil lifespan, however, is more problematic.

Performance on the continuous performance test under parametric increase of working memory load in schizophrenia.

We asked 24 schizophrenia patients and 24 healthy comparison subjects to complete a parametric working memory version of the continuous performance test. Patients exhibited a relatively rapid performance decline with increasing working memory demands. We suggest an interaction between sustained attention and working memory abnormalities in schizophrenia.

Neutralizing mutations of carboxylates that bind metal 2 in T5 flap endonuclease result in an enzyme that still requires two metal ions.

Flap endonucleases (FENs) are divalent metal ion-dependent phosphodiesterases. Metallonucleases are often assigned a "two-metal ion mechanism" where both metals contact the scissile phosphate diester. The spacing of the two metal ions observed in T5FEN structures appears to preclude this mechanism.

Sexual functioning in male survivors of lymphoma: a systematic review (CME).

Introduction: The lymphomas (Hodgkin's lymphoma [HL] and non-Hodgkin's lymphoma [NHL]) are among the most common cancers affecting men under 45 years. Survival rates are now excellent, but treatment is associated with a number of side effects including sexual dysfunction with potential implications for compromised quality of life (QoL).

Aims: To address the (i) prevalence of sexual dysfunction among lymphoma survivors relative to the general population, survivors of other cancers, and in survivors of HL and NHL; and (ii) relationships between sexual functioning and disease and treatment, demographic, and psychological variables.

Performance on the clock drawing task correlates with FMRI response to a visuospatial task in Alzheimer's disease.

The clock drawing (CD) task involves visual integration skills associated with parietal lobe function. Seven mild Alzheimer's Disease (AD) patients and 11 healthy elderly controls (EC) underwent functional magnetic resonance imaging (fMRI) scanning while viewing a radial motion (RM) task. This RM task in EC activated the bilateral secondary visual cortex and parietal regions, whereas AD patients activated only the right-sided secondary visual cortex.