Factors affecting quality of life in rectal cancer survivors who have undergone laparoscopic surgery: patient-reported outcomes over 10 years at a single institution.

INTRODUCTION: Colorectal cancer survivors have many problems affecting their quality of life (QOL). Traditional follow-up focuses on the detection of recurrence rather than QOL. Efforts are being made to assess patient-reported outcomes (PROMS) more formally. Such changes may enable patients to consider QOL factors when deciding on treatment. METHODS: Patients who underwent laparoscopic surgery for rectal cancer between 2005 and 2015 at a single institution were identified and sent European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR29 QOL questionnaires. QOL and the impact of radiotherapy, chemotherapy and formation of end colostomy were assessed. RESULTS: Some 141 patients were identified: 12 died and 118 (83.7%) responded, of whom 101 completed the questionnaires and 17 declined to participate; 11 were lost to follow-up. Mean age was 67 years, median follow-up was 58 months. Median QOL score was 6 (maximum 7) and 4.5% of patients reported a poor QOL score (<4). Significant rectal/perianal pain, sexual dysfunction and urinary symptoms were reported in 3.6%, 10.9% and 2.7% of respondents, respectively. Significant differences between treatment groups were uncommon. All cohorts reported similar QOL, functional and symptom scores. CONCLUSIONS: These results compare favourably with the published data. Future studies may benefit from baseline assessment to better assess treatment impact, prescient in an increasingly elderly and comorbid population. This paper establishes that good PROMs are achievable with laparoscopic surgery for rectal cancer. It identifies limited differences in QOL between treatment modalities. Restoration of intestinal continuity and end colostomy result in similar QOL. This may address common concerns regarding stomata, sexual function and low anterior resection syndrome in this cohort.

Negative pressure therapy for stoma closure sites-a nonrandomised case control study.

AIM: The PICO (Smith & Nephew, UK) dressing is a single use negative pressure wound therapy (NPWT) system that is designed to be used for up to 7 days for closed wounds. We aimed to assess its use for stoma closure wounds. METHOD: We conducted a retrospective analysis of stoma reversal wounds from April 2018 to June 2019. The wound was partially closed with an absorbable subcutaneous suture in a purse-string fashion. A 15 cm × 15 cm PICO dressing was applied directly over this wound. A control group who had received partial purse string closure with packing over the same time period was identified. Patients were contacted and information collected using a questionnaire. The primary outcome measure was the number of visits for dressing changes in the community. Further information was collected about length of stay, time to resolution of pain and return to work. RESULTS: On average, the patients with PICO dressings attended the community nurses 1.9 times. The patients in the PICO group stated it took 1-2 weeks to return to full work/daily activities. The control group averaged attending the community nurse 11.9 times, and 33% had not returned to work/daily activities in 1-2 weeks. CONCLUSION: Those who had a PICO dressing required fewer visits to the community nurse and the majority were able to return to work or resume usual activities within 1 to 2 weeks. This pilot study suggests that negative pressure dressings may be a useful aid for stoma closure site wounds.

A novel Alzheimer disease locus located near the gene encoding tau protein.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Laser system for high resolution Thomson scattering diagnostics on the COMPASS tokamak.

A new Thomson scattering diagnostic has been designed and is currently being installed on the COMPASS tokamak in IPP Prague in the Czech Republic. The requirements for this system are very stringent with approximately 3 mm spatial resolution at the plasma edge. A critical part of this diagnostic is the laser source. To achieve the specified parameters, a multilaser solution is utilized. Two 30 Hz 1.5 J Nd:YAG laser systems, used at the fundamental wavelength of 1064 nm, are located outside the tokamak area at a distance of 20 m from the tokamak. The design of the laser beam transport path is presented. The approach leading to a final choice of optimal focusing optics is given. As well as the beam path to the tokamak, a test path of the same optical length was built. Performance tests of the laser system carried out using the test path are described.

A 130 point Nd:YAG Thomson scattering diagnostic on MAST.

A Thomson scattering diagnostic designed to measure both edge and core physics has been implemented on MAST. The system uses eight Nd:YAG lasers, each with a repetition rate of 30 Hz. The relative and absolute timing of the lasers may be set arbitrarily to produce fast bursts of measurements to suit the time evolution of the physics being studied. The scattered light is collected at F/6 by a 100 kg six element lens system with an aperture stop of 290 mm. The collected light is then transferred to 130 polychromators by 130 independent fiber bundles. The data acquisition and processing are based on a distributed computer system of dual core processors embedded in 26 chassis. Each chassis is standalone and performs data acquisition and processing for five polychromators. This system allows data to be available quickly after the MAST shot and has potential for real-time operations.

MAST YAG Thomson scattering upgrade alignment system.

The recent upgrade to the MAST YAG Thomson scattering while enhancing the diagnostic capabilities increased the complexity of the system. There are eight YAG lasers now operational, doubling the number from the previous setup. This means alignment between each laser individually and reference points is essential to guarantee data quality and diagnostic reliability. To address this issue an alignment system was recently installed. It mimics the beams alignment in MAST by sampling 1% of the laser beam that is sent into a telescope which demagnifies by a factor of 8. The demagnified beam is viewed with a CCD camera. By scanning the camera the profile and position of the beams in the scattering zone and in a range of several meters inside MAST can be determined. Therefore alignment is checked along the beam path without having to sample it inside the vessel. The experimental apparatus and test procedures are described.

Design and implementation of a full profile sub-cm ruby laser based Thomson scattering system for MAST.

A major upgrade to the ruby Thomson scattering (TS) system has been designed and implemented on the Mega-ampere spherical tokamak (MAST). MAST is equipped with two TS systems, a Nd:YAG laser system and a ruby laser system. Apart from common collection optics each system provides independent measurements of the electron temperature and density profile. This paper focuses on the recent upgrades to the ruby TS system. The upgraded ruby TS system measures 512 points across the major radius of the MAST vessel. The ruby laser can deliver one 10 J 40 ns pulse at 1 Hz or two 5 J pulses separated by 100-800 µs. The Thomson scattered light is collected at F/15 over 1.4 m. This system can resolve small (7 mm) structures at 200 points in both the electron temperature and density channels at high optical contrast; ∼50% modulated transfer function. The system is fully automated for each MAST discharge and requires little adjustment. The estimated measurement error for a 7 mm radial point is <4% of T(e) and <3% of n(e) in the range of 40 eV to 2 keV, for a density of n(e)=2×10(19) m(-3). The photon statistics at lower density can be increased by binning in the radial direction as desired. A new intensified CCD camera design allows the ruby TS system to take two snapshots separated with a minimum time of 230 µs. This is exploited to measure two density and temperature profiles or to measure the plasma background light.

Design of a new Nd:YAG Thomson scattering system for MAST.

A new infrared Thomson scattering system has been designed for the MAST tokamak. The system will measure at 120 spatial points with approximately 10 mm resolution across the plasma. Eight 30 Hz 1.6 J Nd:YAG lasers will be combined to produce a sampling rate of 240 Hz. The lasers will follow separate parallel beam paths to the MAST vessel. Scattered light will be collected at approximately f/6 over scattering angles ranging from 80 degrees to 120 degrees. The laser energy and lens size, relative to an existing 1.2 J f/12 system, greatly increases the number of scattered photons collected per unit length of laser beam. This is the third generation of this polychromator to be built and a number of modifications have been made to facilitate mass production and to improve performance. Detected scattered signals will be digitized at a rate of 1 GS/s by 8 bit analog to digital converters (ADCs.) Data may be read out from the ADCs between laser pulses to allow for real-time analysis.

Clinical and genetic heterogeneity in peroneal muscular atrophy associated with vocal cord weakness.

BACKGROUND: The peroneal muscular atrophy syndrome is the most common inherited disorder of the peripheral nervous system and has extensive clinical and genetic heterogeneity. Cranial nerve involvement is rare, though there are distinct peroneal muscular atrophy syndromes in which vocal cord paralysis is a characteristic feature. Among these dHMN-VII and HMSN-IIC are clinically similar but are differentiated by sensory involvement in HMSN-IIC. The gene for dHMN-VII, designated DHMNVP, has been localised to chromosome 2q14, but the location of the gene for HMSN-IIC is currently unknown. It has been suggested that dHMN-VII and HMSN II-C are allelic disorders. OBJECTIVE: To assess the contribution of the dHMN-VII predisposition gene to peroneal muscular atrophy syndromes associated with vocal cord weakness. METHODS: Linkage analysis of microsatellite markers at chromosome 2q14 was undertaken on two families, one affected by HMSN-IIC and a second manifesting vocal cord paralysis and sensorineural deafness in addition to distal muscular atrophy. RESULTS: Two-point LOD scores at chromosome 2q14 markers encompassing the DHMNVP gene were negative in both families. CONCLUSIONS: These results suggest that at least one further gene predisposing to distal muscular weakness in association with vocal cord paralysis is likely to exist, and that dHMN-VII and HMSN-IIC are unlikely to be allelic disorders. Analyses of further HMSN-IIC families are required to confirm this.

Localization of the gene for distal hereditary motor neuronopathy VII (dHMN-VII) to chromosome 2q14.

Distal hereditary motor neuronopathy type VII (dHMN-VII) is an autosomal dominant disorder characterized by distal muscular atrophy and vocal cord paralysis. We performed a genomewide linkage search in a large Welsh pedigree with dHMN-VII and established linkage to chromosome 2q14. Analyses of a second family with dHMN-VII confirmed the location of the gene and provided evidence for a founder mutation segregating in both pedigrees. The maximum three-point LOD score in the combined pedigree was 7.49 at D2S274. Expansion of a polyalanine tract in Engrailed-1, a transcription factor strongly expressed in the spinal cord, was excluded as the cause of dHMN-VII.

Detection of herpes simplex virus mRNA in latently infected trigeminal ganglion neurons by in situ hybridization.

Latent infection of the trigeminal ganglion with herpes simplex virus type 2 (HSV-2) was studied in guinea pigs by in situ DNA hybridization. Frozen ganglion sections from animals killed during the period of latent virus infection were studied under nondenaturing conditions. Some sections were treated with deoxyribonuclease (DNase) or ribonuclease (RNase) before incubation with HSV DNA probes. HSV probes consisted of viral DNA nick translated and labeled in vitro with tritiated nucleotides. Bacteriophage lambda DNA, similarly prepared, was used as a control probe. The lambda probe was negative in all situations, including HSV-2-infected monolayer cells in cell culture. HSV-2 probes produced heavy label and, therefore, evidence of hybridization with HSV-2-infected monolayer cells. When HSV-2 probes were incubated with latently infected ganglion sections, hybridization was detected in 71% of guinea pigs and 46% of ganglia. Label was seen only in neurons, and in positive ganglia 0.3 to 5% of neurons were labeled. The amount of label was markedly decreased by pretreatment of ganglion sections with RNase but not DNase, indicating that the DNA probes hybridized to HSV messenger RNA in the latently infected ganglia.

Mechanisms of herpes simplex virus infectivity enhanced by ultracentrifugal inoculation.

Ultracentrifugation of very dilute suspensions of herpes simplex virus directly onto monolayer cells grown in centrifuge tubes was studied. Enhanced infectivity by ultracentrifugation was similar at 4 degrees C and at 35 to 37 degrees C. The high infectivity levels of cultures centrifuged at 4 degrees C were further examined by infectious center assays. At 4 degrees C, the numbers of infectious centers in control (noncentrifuged) cultures were almost 100-fold fewer than in control cultures at 37 degrees C. However, the numbers of infectious centers in cultures ultracentrifuged at 4 degrees C were similar to those ultracentrifuged at 37 degrees C. The great difference in the numbers of infectious centers between 4 and 37 degrees C control cultures, in contrast to the similarity between 4 and 37 degrees C ultracentrifuged cultures, indicated that ultracentrifugation at 4 degrees C enhanced infectivity possibly by facilitation of herpes simplex virus penetration into monolayer cells.

The final F.F.A.R.A.C.S. examination.

The development of the Final Examination of Fellowship of the Faculty of Anaesthetists of the Royal Australasian College of Surgeons is described from its inception in 1956 to the present. A statistical analysis was made of the examinations in 1969 and 1970. The correlations between marks for essay questions, within the multiple choice examination and between clinical examinations were low, suggesting that the reliability of these tests was unsatisfactory. At this same time, applied anatomy was added to the subjects in this examination. The examination was restructured with more emphasis on the oral and multiple choice examination and the marking system was revised. Continuing analysis has shown higher correlations between and within most parts of the examination. The correlations for the essay marks have remained lower, but essays have been retained in an attempt to assess and encourage the skills involved. Feedback of teaching and learning information obtained from analysis of the examination is provided to Regional Education Officers and Supervisors of Training.