The Royal College of Radiologists National Vulvar Cancer Audit.

AIMS: This audit examined UK vulvar cancer practice from March 2018 to January 2019 and compared it to standards from national and international recommendations. Follow-up data collection in 2020 examined patient outcomes and toxicity. MATERIALS AND METHODS: Audit standards were based on Royal College of Radiologists (RCR) guidance and published literature. A web-based questionnaire was sent to the audit leads at all cancer centres in the UK. Prospective data collection included patient demographics, tumour characteristics, radiotherapy indications, dosimetry, timelines, and follow-up data. The audit targets were 95% compliance with the RCR dose/fractionation schemes in definitive and adjuvant patients, 40% use of intensity modulated radiotherapy (IMRT), 100% of radical patients treated as category 1, and 95% use of gap compensation for category 1 patients. RESULTS: 34/54 UK radiotherapy centres (63%) completed data entry for 152 patients. 23 out of 34 (68%) centres submitted follow-up data for 94 patients. One indicator exceeded the audit target: 98% of radical patients received IMRT. The indicators of RCR dose/fractionation compliance for adjuvant/definitive radiotherapy were achieved by 80%/43% for the primary, 80%/86% for elective lymph nodes, and 21%/21% for pathological lymph nodes. The use of concomitant chemotherapy with radical radiotherapy in suitable patients was achieved by 71%. Other indicators demonstrated that 78% were treated as category 1 and 27% used gap compensation. Acute toxicity was mostly related to skin, gastrointestinal, and genitourinary sites. Grade 3 and Grade 4 toxicities were seen at acceptable rates within the radical and adjuvant groups. Late toxicity was mostly grade 0. CONCLUSION: This audit provides a comprehensive picture of UK practice. IMRT is widely used in the UK, and treatment-related toxicity is moderate. The dose fractionation was very heterogeneous. The designation of vulvar cancer as category 1 was not regularly followed for radical/adjuvant patients, and there was minimal gap compensation during treatment.

Assessment of Quality of Life in Rectal Cancer with Organ-Preservation Treatment: Are We There yet?

Rectal cancer is a common cancer and shows an increased incidence with older age. Although the gold standard treatment is surgical excision, minimally invasive approaches are increasingly used and organ preservation is becoming a reasonable approach. The conservative treatment approach includes local excision, external beam radiotherapy and brachytherapy. However, these all carry a risk of side-effects. It is crucial to provide patients with information to quantify the improvement or detriment in quality of life with their cancer treatment. This can only be done with patient-reported outcome measures (PROMs) as tools within current and future trials. Colorectal cancer has numerous publications with specific PROMs. However, PROMs reporting in rectal cancer is more sparse; PROMs are generally extrapolated from colorectal cancer. Rectal PROMs trials hold small population samples and PROMs as an end point is scarce. We present a review of recent literature based on the PROMs reporting of quality of life for rectal cancer patients and introduce the CITRuS trial as an innovative feasibility study related to electronic PROMs data collection.

Compact laser system for a laser-cooled ytterbium ion microwave frequency standard.

The development of a transportable microwave frequency standard based on the ground-state transition of 171Yb+ at ∼12.6 GHz requires a compact laser system for cooling the ions, clearing out of long-lived states and also for photoionisation. In this paper, we describe the development of a suitable compact laser system based on a 6U height rack-mounted arrangement with overall dimensions 260 × 194 × 335 mm. Laser outputs at 369 nm (for cooling), 399 nm (photoionisation), 935 nm (repumping), and 760 nm (state clearout) are combined in a fiber arrangement for delivery to our linear ion trap and we demonstrate this system by cooling of 171Yb+ ions. Additionally, we demonstrate that the lasers at 935 nm and 760 nm are close in frequency to water vapor and oxygen absorption lines, respectively; specifically, at 760 nm, we show that one 171Yb+ transition is within the pressure broadened profile of an oxygen line. These molecular transitions form convenient wavelength references for the stabilization of lasers for a 171Yb+ frequency standard.

Note: A high-performance, low-cost laser shutter using a piezoelectric cantilever actuator.

We report the design and characterization of an optical shutter based on a piezoelectric cantilever. Compared to conventional electro-magnetic shutters, the device has intrinsically low power and is acoustically quiet. The cantilever position is controlled by a high-voltage op-amp circuit for easy tuning of the range of travel, and mechanical slew rate, which enables a factor of 30 reduction in mechanical noise compared to a rapidly switched device. We achieve shuttering rise and fall times of 11 µs, corresponding to mechanical slew rates of 1.3 ms-1, with a timing jitter of less than 1 µs. When used to create optical pulses, we achieve minimum pulse durations of 250 µs. The reliability of the shutter was investigated by operating continuously for one week at 10 Hz switching rate. After this period, neither the shutter delay or actuation speed had changed by a measurable amount.

Heritability of the spatial distribution and peak density of macular pigment: a classical twin study.

PURPOSE: To elucidate the heritability of peak density and spatial width of macular pigment (MP) using a Classical Twin Study. METHODS: Fundus autofluorescence images were obtained at 488 nm from 86 subjects or 43 twin pairs (21 monozygotic (MZ) and 22 dizygotic (DZ)) (27 male, 59 female) aged from 55 to 76 years (mean 62.2 ± 5.3 years). The relative topographic distribution of MP was measured using a grey scale of intensity (0-255 units) in a 7° eccentricity around the fovea. Relative peak MP density (rPMPD) and relative spatial distribution of MP (rSDMP) were used as the main outcome measure in the statistical analysis. RESULTS: A significantly higher correlation was found within MZ pairs as compared with that within DZ pairs for rPMPD, (r=0.99, 95% confidence interval (95% CI) 0.93 to 1.00) and 0.22, 95% CI -0.34 to 0.71), respectively, suggesting strong heritability of this trait. When rSDMP was compared, there was no significant difference between the correlations within MZ pairs (r=0.48, 95% CI -0.02 to 0.83) and DZ pairs (r=0.63, 95% CI 0.32 to 0.83), thus rSDMP is unlikely to have a considerable heritable component. In addition, there was no difference between any MP parameter when normal maculae were compared with early age-related macular degeneration (AMD) (rPMPD 0.36 vs 0.34, t=1.18 P=0.243, rSDMP 1.75 vs 1.75, t=0.028 P=0.977). CONCLUSIONS: rPMPD is a strongly heritable trait whereas rSDMP has minimal genetic influence and a greater influence by environmental factors. The presence of macular changes associated with early AMD did not appear to influence any of these pigment parameters.

Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.

The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.

The hepatocyte growth factor receptor (MET) gene is not associated with refractive error and ocular biometrics in a Caucasian population.

PURPOSE: The purpose of this study was to determine if genetic variants in the hepatocyte growth factor receptor (MET) gene are associated with refractive error and ocular biometric measures in a Caucasian cohort. METHODS: A case-control association study using 818 Caucasian adults (37.2% male, 62.8% female; average age: 51.21+/-17.17 years) was undertaken. All individuals were genotyped for 16 tag single nucleotide polymorphisms (tSNPs) across the MET gene region. Myopia was defined as -0.5 DS or worse in both eyes and divided into high myopia (

The retinoic acid receptor alpha (RARA) gene is not associated with myopia, hypermetropia, and ocular biometric measures.

PURPOSE: The Retinoic Acid Receptor Alpha (RARA) gene is a potential candidate gene for myopia due to its differential expression in animal models during experimentally induced myopia. To test for whether RARA is associated with myopia we have undertaken a case-control study assessing for associations between RARA and myopia, hypermetropia, and ocular biometric measures. METHODS: A total of 802 Anglo-Celtic individuals were genotyped. Five tag single nucleotide polymorphisms (tSNPs) in RARA with an r(2) of 0.8 and a minor allele frequency greater than 5% were selected for genotyping. Genotype frequencies of these 5 tSNPs were compared between individuals with emmetropia and those with myopia or hypermetropia. A quantitative analysis was also performed to assess associations with ocular biometric measures including axial length, corneal curvature and anterior chamber depth. RESULTS: We did not identify any significant association between tSNPs in RARA with either myopia or hypermetropia as qualitative traits. Neither did we identify any significant associations of these tSNPs with the quantitative traits of axial length, corneal curvature and anterior chamber depth. CONCLUSIONS: This is the first study to assess for associations between RARA and myopia, hypermetropia, and ocular biometric measures. Our findings suggest that variations in the nucleotide sequence of RARA are not associated with myopia, hypermetropia, or ocular biometric measures in our population.

Role of genetic factors in lower- and higher-order aberrations--the genes in myopia twin study.

AIMS: We intended to investigate the relative genetic contribution in wavefront aberrations using a sub-group of twins recruited in the Genes in Myopia twin study, and subsequently provide direction for future studies into the aetiology of mono-chromatic aberrations. To our knowledge, the Genes in Myopia twin study is the first study to explore the role of genetic factors in both lower- and higher-order aberrations in a Caucasian population. METHODS: Each individual completed a general questionnaire and underwent a comprehensive eye examination. Higher-order wavefront aberrations were calculated with Zernike coefficients up to the fourth order. RESULTS: A total of 46 twin pairs with a mean age of 65.3 years were included in the analysis. Monozygotic intra-pair correlations were significantly higher compared to those in dizygotic twin pairs for defocus aberrations (p < 0.05). A trend for a genetic component was identified for higher-order aberrations. CONCLUSION: Genetic studies into refraction typically explore the genetic effects of lower-order aberrations such as myopia and hypermetropia; however, there is little to no research into the genetic basis of higher-order aberrations. The Genes in Myopia twin study indicates a potential genetic role for higher-order aberrations and provides useful insights into the aetiology of refractive error.

The role of birth weight in myopia--the genes in myopia twin study.

OBJECTIVE: It was the aim of this study to assess the role of birth weight in the development of myopia using a large cohort of Caucasian monozygotic (MZ) and dizygotic (DZ) twins that took part in the Genes in Myopia (GEM) twin study. METHODS: The recruitment of all twins in the GEM twin study was facilitated by the Australian Twin Registry. Each twin underwent a standard questionnaire and a comprehensive ocular examination, which included a dilated objective refraction through autorefraction. Myopia was defined as spherical equivalent equal to or worse than -0.50 diopters. Birth weight was determined through self-report as part of the standard questionnaire. RESULTS: A total of 1,224 twins (690 MZ and 534 DZ twins) aged between 18 and 86 years (mean age 52.36 years) were recruited into the GEM study. The mean birth weight was similar between MZ (2.34 kg) and DZ twins (2.46 kg; p > 0.05). Logistic regression showed no significant association with birth weight and myopia for all twins (p = 0.26), as well as for MZ (p = 0.18) and DZ twins (p = 0.70) separately, with no gender effect (p = 0.23). Moreover, there was no significant difference in mean birth weight between discordant (presence/absence) MZ (myopes = 2.33 kg, non-myopes = 2.39 kg) and DZ twin pairs (myopes = 2.39 kg, non-myopes = 2.43 kg; p = 0.91 and 0.95, respectively). CONCLUSION: Birth weight appears to have little to no role in the development of myopia. In addition, birth weight was not a predictor of the discordance of myopia in MZ and DZ twin pairs.

The dot-and-fleck retinopathy of X linked Alport syndrome is independent of complement factor H (CFH) gene polymorphisms.

BACKGROUND AND AIMS: X linked Alport syndrome is characterised by renal failure, hearing loss, lenticonus, and a central and peripheral dot-and-fleck retinopathy. complement factor H (CFH) gene variants are strongly associated with retinal drusen in macular degeneration and mesangiocapillary glomerulonephritis, and this study examines their role in the development of the Alport retinopathy. METHODS: Twenty-three males and 27 females from 27 unrelated families were examined and their DNA tested for the CFH risk allele (1277 T>C, h1, Y402H) and protective haplotypes (h2 and h4) using a MALDI-TOF-based method. RESULTS: The prevalence of the CFH risk allele was not increased in males with a central or peripheral retinopathy. Three of the nine (33%) with the central retinopathy had at least one copy of the risk allele, and five of the 14 (36%) without the retinopathy did (NS, OR 0.900, CI 0.154 to 5.259). Four of the 12 (33%) with either retinopathy had the risk allele, and two of the six (33%) with none did (NS OR 1.0, CI 0.125 to 7.996). CONCLUSION: The pathogenesis of the retinal dots and flecks in Alport syndrome is independent of CFH-dependent mechanisms and, like other clinical features, may depend on the nature of the underlying COL4A5 mutations.

Testing protocol and recruitment in the genes in myopia twin study.

PURPOSE: The genes in myopia twin study were established to assess the relative genetic contribution of spherical equivalent using a classical twin model. This manuscript will provide a detailed outline of the methodological design, twin recruitment, and the prevalence of myopia in the genes in myopia twin study. METHODS: All Victorian-based twins registered with the Australian Twin Registry aged 18 years or older were invited to participate genes in myopia twin study. Each subject underwent a general questionnaire, comprehensive eye examination, and a blood sample was collected. Myopia was defined as worse than or equal to -0.50 diopters sphere (in at least one eye). RESULTS: A total of 627 twin pairs out of 4,158 twin pairs consented to participate in the genes in myopia twin study. A total of 345 monozygotic and 267 dizygotic twin pairs aged between 18 and 86 years were examined. The response rate for monozygotic twins (19.8%) was almost double that of dizygotic twins (11.7%). The overall prevalence of myopia was 29.7% for all twins. CONCLUSIONS: The genes in myopia twin study is the first Australian-based twin study to assess refraction in an adult twin population and the largest of its kind in the world. The comprehensive testing protocol used in the in the genes in myopia twin study has provided an extensive twin database for genetic analysis. Participation rate was found to vary according to zygosity, gender, and age.

Single-crystal lead magnesium niobate-lead titanate (PMN/PT) as a broadband high power transduction material.

Two experimental underwater acoustic projectors, a tonpilz array, and a cylindrical line array, were built with single crystal, lead magnesium niobate/lead titanate, a piezoelectric transduction material possessing a large electromechanical coupling factor (k33 = 0.9). The mechanical quality factor, Q(m), and the effective coupling factor, k(eff), determine the frequency band over which high power can be transmitted; k(eff) cannot be greater than the piezoelectric material value, and so a high material coupling factor is a requisite for broadband operation. Stansfield's bandwidth criteria are used to calculate the optimum Q(m) value, Q(opt) approximately 1.2 (1-k(eff)2 1/2/k(eff). The results for the tonpilz projector exhibited k(eff) = 0.730, Q(m) = 1.17 (very near optimal), and a fractional bandwidth of 0.93. For the cylindrical transducer array, k(eff) = 0.867, Q(m) = 0.91 (larger than the optimum value, 0.7), and the bandwidth was 1.16. Although the measured bandwidths were less than optimal, they were accurately predicted by the theory, despite the highly simplified nature of the Van Dyke equivalent circuit, on which the theory is based.

The role of MRI in the diagnosis of proximal femoral fractures in the elderly.

The diagnosis of an undisplaced hip fracture cannot always be made on plain radiographs alone. The use of MRI scanning in detecting occult hip fractures is well documented. However, no previous studies have suggested which specific patient group would benefit most from this investigation. Thirty-five patients with hip pain and normal plain radiographs underwent MRI scanning. Pathology was detected in 29 of the patients, of which 21 involved a neck of femur fracture. Patients were divided into two groups based on age. In patients over 70 years, pathology detected resulted in surgical intervention in 13 cases. This is in contrast with those below the age of 70 years, in whom no neck of femur fractures were found and no surgical intervention was indicated (p<0.001). We recommend that an MRI scan be performed on such patients, above 70 years of age. These are the patients in whom management is significantly altered due to the imaging process used.

Analysis of the EFEMP1 gene in individuals and families with early onset drusen.

AIMS: Age-related macular degeneration (AMD) is considered a complex genetic disease, although the genetic influences are not yet fully understood. Genetic analysis is hampered by the late onset of disease and the difficulty in obtaining multigenerational families. To investigate this problem further we studied our population of early onset drusen cases. The Arg345Trp mutation on exon 10 of the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene causes two clinical phenotypes of early onset drusen (Doyne honeycomb retinal dystrophy and Malattia Leventinese), yet does not appear to be involved in other early onset drusen phenotypes or typical AMD. We wished to ascertain the involvement of the EFEMP1 gene in our population of sporadic and familial subjects presenting with early onset drusen and their affected relatives. METHODS: Individuals presenting with drusen/end-stage maculopathy at 60 years or under were identified from retinal clinics in Melbourne. All available first- and second-degree relatives were also examined. In all, 116 ethnically matched controls were collected from the same community for comparison. RESULTS: Single stranded conformational polymorphism (SSCP) analysis and subsequent sequencing revealed four previously described and three novel sequence variations. Most occurred at similar frequencies in the case and control populations and were not thought to be disease associated. CONCLUSION: The term early onset drusen encompasses a wide range of phenotypes and our findings indicate that it is likely that more than one gene is involved in its causation. It is essential that these clinical phenotypes are well described and categorised to allow greater possibility of success in the search for other disease genes.

Nerve growth factor expression and innervation of the painful intervertebral disc.

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.

Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs.

AIMS: To investigate the phenotype of cells in normal and degenerate intervertebral discs by studying the expression of molecules characteristic of chondrocytes in situ. METHODS: Human intervertebral discs taken at surgery were graded histologically, and classified on this basis as normal or degenerate. Eighteen of each type were selected, and in situ hybridisation was performed for the chondrocytic markers Sox9 and collagen II using (35)S labelled cDNA probes. Aggrecan was located by immunohistochemistry, using the monoclonal antibody HAG7E1, and visualised with an avidin-biotin peroxidase system. RESULTS: In the normal discs, strong signals for Sox9 and collagen II mRNA, and strong staining for the aggrecan protein were seen for the cells of the nucleus pulposus (NP), but reactions were weak or absent over the cells of the annulus fibrosus (AF). In degenerate discs, the Sox9 and collagen II mRNA signals remained visible over the cells of the NP and were again absent in the AF. Aggrecan staining was not visible in the NP cells, and was again absent in the AF. CONCLUSIONS: Cells of the normal NP showed expression of all three markers, clearly indicating a chondrocytic phenotype. In degeneration, there was evidence of a loss of aggrecan synthesis, which may contribute to the pathogenesis of disc degeneration. AF cells showed no evidence of a chondrocytic phenotype in either normal or degenerate discs.

Generating mouse models of retinal disease using ENU mutagenesis.

We used the chemical mutagen, N-ethyl-N-nitrosourea, to induce random point mutations in the germline of the mouse strain C57BL/6 in order to generate models of retinal diseases. 1163 mutagenised first generation mice produced using this approach were examined for eye abnormalities. Approximately one-third (412) presented with some form of ocular abnormality. Most changes were unilateral and confined to the anterior segment of the eye. Less than 10% (44) of identified changes affected the posterior segment of the eye. 21 mice with varying ocular abnormalities, including 17 with retinal changes, were bred to produce second generation mice to confirm genetic inheritance. Genetic inheritance was confirmed in several of these lines including three with retinal changes.