Rapid detection of metallo-β-lactamase-producing by the combination of MALDI-TOF MS and CarbaNP.

Aims: Carbapenem resistance in is emerging and is mainly attributed to insertion sequence (IS)-mediated activation of the carbapenemase gene . We investigated the use of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and the CarbaNP assay for the rapid identification of these strains.

Methods: This study used the Bruker MALDI Biotype system and the mass spectra models generated by 20 reference strains (10 -positive and 10 -negative) in the ClinProTools software to identify 404 (71 -positive and 333 -negative) clinical isolates.

Carbetocin versus oxytocin for prevention of post-partum haemorrhage at caesarean section in the United Kingdom: An economic impact analysis.

Objective: To determine the economic impact of the introduction of carbetocin for the prevention of postpartum haemorrhage (PPH) at caesarean section, compared to oxytocin.

Study Design: The model is a decision tree conducted from a UK National Health Service perspective. 1500 caesarean sections (both elective and emergency) were modelled over a 12 month period.

The Influence of the Microbiome on Type 1 Diabetes.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β cells. The rapid rise in T1D incidence during the past 50 y suggests environmental factors contribute to the disease. The trillion symbiotic microorganisms inhabiting the mammalian gastrointestinal tract (i.

Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases.

switchde: inference of switch-like differential expression along single-cell trajectories.

Motivation: Pseudotime analyses of single-cell RNA-seq data have become increasingly common. Typically, a latent trajectory corresponding to a biological process of interest-such as differentiation or cell cycle-is discovered. However, relatively little attention has been paid to modelling the differential expression of genes along such trajectories.

Order Under Uncertainty: Robust Differential Expression Analysis Using Probabilistic Models for Pseudotime Inference.

Single cell gene expression profiling can be used to quantify transcriptional dynamics in temporal processes, such as cell differentiation, using computational methods to label each cell with a 'pseudotime' where true time series experimentation is too difficult to perform. However, owing to the high variability in gene expression between individual cells, there is an inherent uncertainty in the precise temporal ordering of the cells. Pre-existing methods for pseudotime estimation have predominantly given point estimates precluding a rigorous analysis of the implications of uncertainty.

A Novel Selective Medium for Isolation of Bacteroides fragilis from Clinical Specimens.

A novel Bacteroides fragilis selective (BFS) medium, consisting of a brain heart infusion agar base supplemented with yeast extract, cysteine hydrochloride, bile salts, vitamin K, hemin, glucose, esculin, ferric ammonium citrate, bromothymol blue, gentamicin, kanamycin, and novobiocin, was evaluated. When BFS agar was tested with a collection of 303 bacteria of different genera, it allowed the growth of B. fragilis as large yellow colonies, with blackening of the medium after 48 h of anaerobic incubation, while the growth of most other anaerobes, facultative anaerobes, and aerobes was inhibited.

Two-step chlorination: A new approach to disinfection of a primary sewage effluent.

Sewage disinfection aims at inactivating pathogenic microorganisms and preventing the transmission of waterborne diseases. Chlorination is extensively applied for disinfecting sewage effluents. The objective of achieving a disinfection goal and reducing disinfectant consumption and operational costs remains a challenge in sewage treatment.

Co-expression modules identified from published immune signatures reveal five distinct immune subtypes in breast cancer.

Purpose: There is a growing body of literature demonstrating that immune-related expression signatures predict breast cancer prognosis and chemo-/targeted-therapy responsiveness. However, it is unclear whether these signatures correlate with each other or represent distinct immune-related signals.

Methods: We evaluated 57 published immune-related expression signatures in four public breast cancer datasets totaling 3295 samples.

TNF-α modulates genome-wide redistribution of ΔNp63α/TAp73 and NF-κB cREL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer.

The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ΔNp63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs comodulated by cREL/ΔNp63/TAp73 transcription factors we uncovered in head and neck squamous cell carcinomas (HNSCCs). However, how inflammatory gene signatures and cREL/p63/p73 targets are comodulated genome wide is unclear.

PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression.

Triple-negative breast cancer (TNBC), in which cells lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and the ERBB2 (also known as HER2) receptor, is the breast cancer subtype with the poorest outcome. No targeted therapy is available against this subtype of cancer owing to a lack of validated molecular targets. We previously reported that signaling involving MYC-an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes-is disproportionally higher in triple-negative (TN) tumors than in receptor-positive (RP) tumors.

Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma.

Nidogen-2 (NID2) is a key component of the basement membrane that stabilizes the extracellular matrix (ECM) network. The aim of the study is to analyze the functional roles of NID2 in the pathogenesis of nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). We performed genome-wide methylation profiling of NPC and ESCC and validated our findings using the methylation-sensitive high-resolution melting (MS-HRM) assay.

Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing.

The cost of local, multi-professional obstetric emergencies training.

Introduction: We aim to outline the annual cost of setting up and running a standard, local, multi-professional obstetric emergencies training course, PROMPT (PRactical Obstetric Multi-Professional Training), at Southmead Hospital, Bristol, UK - a unit caring for approximately 6500 births per year.

Material And Methods: A retrospective, micro-costing analysis was performed. Start-up costs included purchasing training mannequins and teaching props, printing of training materials and assembly of emergency boxes (real and training).

Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies.

Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC).

Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours.

Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management.

Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche.

The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is overexpressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo.

Test-Retest Reliability of an Automated Infrared-Assisted Trunk Accelerometer-Based Gait Analysis System.

The aim of this study was to determine the test-retest reliability of an automated infrared-assisted, trunk accelerometer-based gait analysis system for measuring gait parameters of healthy subjects in a hospital. Thirty-five participants (28 of them females; age range, 23-79 years) performed a 5-m walk twice using an accelerometer-based gait analysis system with infrared assist. Measurements of spatiotemporal gait parameters (walking speed, step length, and cadence) and trunk control (gait symmetry, gait regularity, acceleration root mean square (RMS), and acceleration root mean square ratio (RMSR)) were recorded in two separate walking tests conducted 1 week apart.

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

Background: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes.

Adaptive Randomization of Neratinib in Early Breast Cancer.

Background: The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e.

Prevalence of infections among residents of Residential Care Homes for the Elderly in Hong Kong.

Introduction: A point prevalence study was conducted to study the epidemiology of common infections among residents in Residential Care Homes for the Elderly in Hong Kong and their associated factors.

Methods: Residential Care Homes for the Elderly in Hong Kong were selected by stratified single-stage cluster random sampling. All residents aged 65 years or above from the recruited homes were surveyed.

Ophthalmology simulation for undergraduate and postgraduate clinical education.

This is a review education paper on the current ophthalmology simulators utilized worldwide for undergraduate and postgraduate training. At present, various simulators such as the EYE Exam Simulator (Kyoto Kagaku Co. Ltd.

A pairwise likelihood-based approach for changepoint detection in multivariate time series models.

This paper develops a composite likelihood-based approach for multiple changepoint estimation in multivariate time series. We derive a criterion based on pairwise likelihood and minimum description length for estimating the number and locations of changepoints and for performing model selection in each segment. The number and locations of the changepoints can be consistently estimated under mild conditions and the computation can be conducted efficiently with a pruned dynamic programming algorithm.

The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur: a randomised prospective mixed method pilot study.

Aims: We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks.

Patients And Methods: We undertook a pilot study comparing the functional recovery after trochanteric hip fracture in patients 60 years or older, admitted with a trochanteric hip fracture, and potentially eligible to be randomised to either standard care or the administration of subcutaneous PTH for six weeks.