Evaluation of monte carlo to support commissioning of the treatment planning system of new pencil beam scanning proton therapy facilities.

. To demonstrate the potential of Monte Carlo (MC) to support the resource-intensive measurements that comprise the commissioning of the treatment planning system (TPS) of new proton therapy facilities..

Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies.

Retinoblastoma, the most common childhood eye cancer, presents in two forms: heritable or sporadic. Heritable retinoblastoma is caused by a germline mutation in the gene. Early diagnosis of children at risk of inheriting an mutation is crucial to achieve optimal clinical outcome.

Clinical Service Delivery of Noninvasive Prenatal Diagnosis by Relative Haplotype Dosage for Single-Gene Disorders.

A relative haplotype dosage (RHDO)-based method was developed and implemented into routine clinical practice for noninvasive prenatal diagnosis (NIPD) of multiple single-gene disorders: spinal muscular atrophy, Duchenne and Becker muscular dystrophies, and cystic fibrosis. This article describes the experiences of the first 152 pregnancies to have NIPD by RHDO as part of a routine clinical service. Provision of results within a clinically useful time frame (mean, 11 calendar days) was shown to be possible, with a very low failure rate (4%), none being due to a technical failure.

Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma.

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types.

Short-Term Clinical Outcomes of a Novel Corneal Prosthetic Device in a Rabbit Model.

Purpose: To evaluate the clinical performance and biocompatibility of a novel synthetic corneal device.

Methods: Synthetic, single-piece, foldable, suturable, optic-and-skirt design prototype devices were fabricated using expanded polytetrafluoroethylene. A combination of intralamellar and full-thickness penetrating techniques was used for implantation.

Implementation of cell-free DNA-based non-invasive prenatal testing in a National Health Service Regional Genetics Laboratory.

Background: Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory.

Geometric and dosimetric evaluation of the differences between rigid and deformable registration to assess interfraction motion during pelvic radiotherapy.

Background And Purpose: Appropriate internal margins are essential to avoid a geographical miss in intensity-modulated radiation therapy (IMRT) for endometrial cancer (EC). This study evaluated interfraction target motion using rigid and non-rigid approximation strategies and calculated internal margins based on random and systematic errors using traditional rigid margin recipes. Dosimetric impact of target motion was also investigated.

Non-invasive prenatal diagnosis of spinal muscular atrophy by relative haplotype dosage.

Although technically possible, few clinical laboratories across the world have implemented non-invasive prenatal diagnosis (NIPD) for selected single-gene disorders, mostly owing to the elevated costs incurred. Having previously proven that NIPD for X-linked disorders can be feasibly implemented in clinical practice, we have now developed a test for the NIPD of an autosomal-recessive disorder, spinal muscular atrophy (SMA). Cell-free DNA was extracted from maternal blood and prepared for massively parallel sequencing on an Illumina MiSeq by targeted capture enrichment of single-nucleotide polymorphisms across a 6 Mb genomic window on chromosome 5 containing the SMN1 gene.

Lower glycolysis carries a higher flux than any biochemically possible alternative.

The universality of many pathways of core metabolism suggests a strong role for evolutionary selection, but it remains unclear whether existing pathways have been selected from a large or small set of biochemical possibilities. To address this question, we construct in silico all possible biochemically feasible alternatives to the trunk pathway of glycolysis and gluconeogenesis, one of the most highly conserved pathways in metabolism. We show that, even though a large number of alternative pathways exist, the alternatives carry lower flux than the real pathway under typical physiological conditions.

[Pigmented villonodular synovitis].

Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumour is an articular pathology that occurs predominantly in young adults and is caused by an abnormal proliferation of the synovial membrane. The clinical presentation includes pain and joint swelling. MRI represents the best imaging modality to investigate this disease but the histopathology of synovial tissue provides the definitive diagnosis.

A review of smoking cessation services in women attending colposcopy clinics in Scotland.

The most common reason for women being referred to colposcopy clinics is an abnormal smear suggesting pre-cancerous change within the cervix. It has been demonstrated that in women with low-grade lesions, smoking cessation led to a reduction in size of the cervical lesion over a 6-month period. Smoking is also recognised as an independent risk factor for treatment failure of cervical intraepithelial neoplasia.

Space-time clustering analyses of type 1 diabetes in children from north-east England: support for an infectious aetiology?

Background: The aetiology of type 1 diabetes in children is uncertain. A number of recent studies have suggested an infectious aetiology. It has been postulated that an infectious agent may be involved.

Assessment of pelvic floor movement using transabdominal and transperineal ultrasound.

The aims of the study were (1) to assess the reliability of transabdominal (TA) and transperineal (TP) ultrasound during a pelvic floor muscle (PFM) contraction and Valsalva manoeuvre and (2) to compare TA ultrasound with TP ultrasound for predicting the direction and magnitude of bladder neck movement in a mixed subject population. A qualified sonographer assessed 120 women using both TA and TP ultrasound. Ten women were tested on two occasions for reliability.

Prevalence of Chlamydia trachomatis infection in small rural town family planning clinics in the central belt of Scotland.

Objective: To estimate the prevalence of chlamydia infection in women under 25 attending community-based family planning/sexual health clinics in West Lothian.

Design: Two hundred and three women under 25 attending over a six month period were offered a urine test for chlamydia trachomatis. The tests were performed using the ligase chain reaction method.

Intra-uterine death resulting from placental metastases in adenocarcinoma of unknown primary.

A thirty-five year old woman presented with bilateral neck, chest wall and back masses. She was 16 weeks pregnant. Lymph node excision revealed metastatic poorly differentiated adenocarcinoma of unknown primary.

Two brothers with varying combinations of severe developmental delay, epilepsy, microcephaly, tetralogy of Fallot and hydronephrosis.

We report on a sib pair who manifest a pattern of anomalies which appears to be unique and for which we are unable to provide a cytogenetic or molecular genetic explanation. While a number of their physical features are distinct, their overall appearance and pattern of neurological impairment suggest they suffer from the same genetic disorder.

Gene-directed enzyme prodrug therapy: quantitative bystander cytotoxicity and DNA damage induced by CB1954 in cells expressing bacterial nitroreductase.

Clones of human colon carcinoma (WiDr), ovarian carcinoma (SK-OV-3), and Chinese hamster V79 cells expressing the nitroreductase enzyme (NR) from E. coli B were 52-, 225- and 177-fold respectively more sensitive to a 24-h incubation with the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) than the parent lines. The IC50s of non-NR-expressing bystander cells were measured in the presence of differing proportions of NR-expressing cells.