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Purpose: We assessed the sensibility, utility, and implementation considerations of the Short-Form HIV Disability Questionnaire (SF-HDQ) in community-based settings. Methods: We conducted a mixed-methods study with adults living with HIV and community providers in seven community sites in Canada. We administered the SF-HDQ, a sensibility questionnaire and conducted semi-structured interviews. The SF-HDQ was sensible if median scores were ≥5/7(adults living with HIV) and ≥4/7(community providers) for ≥80% of the sensibility questionnaire items. Qualitative interview data were analyzed using content analysis. Results: Median sensibility scores were ≥5 for adults living with HIV (n = 44) and ≥4 for community providers (n = 10) for 95% and 100% of items, respectively. The SF-HDQ is comprehensive, represented disability, captured its episodic nature, and was easy to complete. Community utility included: facilitating communication and engagement with community; taking a snapshot of disability and tracking changes over time; guiding referrals; fostering self-reflection; and informing community programs. Considerations for implementation included flexible, person-centered approaches to mode and processes of administration, and communicating scores based on personal preferences among persons living with HIV. Conclusion: The SF-HDQ possesses sensibility and utility for use in community-based settings.

Background. Despite substantial evidence demonstrating clear benefit, rates of preemptive kidney transplantation (PreKTx) remain low in the United States. Our goal was to identify barriers to PreKTx. Methods. Using a telephone-administered questionnaire including questions about barriers, timing of referral, timing of education, we retrospectively studied first living donor kidney transplant recipients (2006-2010) at Mayo Clinic, Rochester, MN. Of 235 patients, 145 (62%) responded to the questionnaire (74 PreKTx and 71 non-PreKTx). We compared categorical data with Fisher exact test and median times with Wilcoxon rank sum test. Results. Polycystic kidney disease (PCKD), longer median time between diagnosis and transplant, and time between education about transplant and transplant correlated with PreKTx (P < 0.01). The presence of at least 1 patient-identified barrier (lack of referral, financial barriers, medical barriers, no identified living donor and donor evaluation delays) was associated with non-PreKTx (0.034) though no single barrier predominated. Age, education level, insurance status and source of referral (primary care, nephrology, and nonphysician referral) were not associated with the rate of PreKTx. Univariate logistic regression identified white race, PCKD, and increased time from diagnosis as factors favoring PreKTx; PCKD and increased time remained significant factors after multivariate analysis. Conclusions. Even among a patient population that is primarily white, educated, and has a spouse or first-degree relative donor, PreKTx rates remain concerningly low. Increased time between diagnosis or education and transplant are predictors of PreKTx. Greater emphasis on transplant education earlier in the stages of chronic kidney disease and community outreach from transplant centers may help to increase the rate of PreKTx.

the article discusses a study to find influence of pelvic vein reflux in prevalence of haemorrhoids in women and which conclude a relationship between internal Iliac vein reflux and haemorrhoids. It states that association of haemorrhoids with pelvic veins was identified. It mentions that symptomatic haemorrhoids may be a result of untreated reflux. It informs foam sclerotherapy and pelvic vein embolisation as treatment for cause resulting in pelvic vein incompetence.

Background: Small saphenous vein (SSV) disconnection and removal are challenging and considered by some authors to have too high a morbidity and failure rate to justify their routine use. Our audited results are at variance with these views.Methods: We describe a reliable, ultrasound guided, minimally invasive technique for ligation and stripping of the SSV with an incision usually <1 cm. From our total series, 50 random patients attended for ultrasound review. The sapheno-popliteal junction (SPJ), strip track and signs of recurrence were assessed and recorded.Results: Since 1999, 627 patients (679 limbs) have undergone surgery for ultrasound proven SSV reflux. Fifty-two limbs (50 patients) were ultrasound assessed post-operatively. Fifty-one had flush ligation of the SPJ with one showing a 'stump' <1 cm. All showed successful SSV removal. Three limbs had minor strip track revascularisation but none had obvious clinical recurrence. Of the whole series, 11/627 (1.8%) developed proven deep vein thrombosis (DVT). There were six superficial wound infections and one strip track abscess. Sural nerve neurapraxia occurred in 13/627 (2.1%); one showing no sign of recovery at four weeks post-operatively.Conclusions: Ultrasound guided SSV is a safe, minimally invasive technique with high success and low recurrence and complication rates [ABSTRACT FROM AUTHOR]

We describe an unusual pattern of venous abnormality and the use of endovenous radiofrequency ablation, using the TRans-Luminal Occlusion of Perforator technique to treat multiple refluxing perforators in a 29-year-old patient with Klippel-Trenaunay syndrome. Klippel-Trenaunay syndrome is a rare congenital anomaly characterised by a triad of features including unilateral limb overgrowth, venous varicosities and capillary malformations of the affected limb. Ultrasound findings demonstrated 22 incompetent perforator veins in the lateral aspect of the patients left leg, communicating with a complex network of large calibre varicosities causing unilateral leg oedema and pain. Staged radiofrequency ablation procedures using the Olympus Celon RFITT (radiofrequency-induced thermotherapy; please see Technical Note) device under local anaesthetic were performed. These procedures were followed with two sessions of foam sclerotherapy. This case report describes the efficacy of this treatment regime and this patient’s significantly improved morbidity 18 months after initial treatment. [ABSTRACT FROM PUBLISHER]

The clinical approvals of KRAS G12C inhibitors have been a revolutionary advance in precision oncology, but response rates are often modest. To improve patient selection, we developed an integrated model to predict KRAS dependency. By integrating molecular profiles of a large panel of cell lines from the DEMETER2 dataset, we built a binary classifier to predict a tumor's KRAS dependency. Monte Carlo cross validation via ElasticNet within the training set was used to compare model performance and to tune parameters α and λ. The final model was then applied to the validation set. We validated the model with genetic depletion assays and an external dataset of lung cancer cells treated with a G12C inhibitor. We then applied the model to several Cancer Genome Atlas (TCGA) datasets. The final "K20" model contains 20 features, including expression of 19 genes and KRAS mutation status. In the validation cohort, K20 had an AUC of 0.94 and accurately predicted KRAS dependency in both mutant and KRAS wild-type cell lines following genetic depletion. It was also highly predictive across an external dataset of lung cancer lines treated with KRAS G12C inhibition. When applied to TCGA datasets, specific subpopulations such as the invasive subtype in colorectal cancer and copy number high pancreatic adenocarcinoma were predicted to have higher KRAS dependency. The K20 model has simple yet robust predictive capabilities that may provide a useful tool to select patients with KRAS mutant tumors that are most likely to respond to direct KRAS inhibitors., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: C.V.P. is the founder of EnFuego Therapeutics, Inc, which is focused on the development of KRAS therapeutics and holds equity in the company. The remaining authors disclose no potential conflicts of interest., (Copyright: © 2023 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Model systems are an essential resource in cancer research. They simulate effects that we can infer into humans, but come at a risk of inaccurately representing human biology. This inaccuracy can lead to inconclusive experiments or misleading results, urging the need for an improved process for translating model system findings into human-relevant data. We present a process for applying joint dimension reduction (jDR) to horizontally integrate gene expression data across model systems and human tumor cohorts. We then use this approach to combine human TCGA gene expression data with data from human cancer cell lines and mouse model tumors. By identifying the aspects of genomic variation joint-acting across cohorts, we demonstrate how predictive modeling and clinical biomarkers from model systems can be improved., (© 2023. The Author(s).)

Activity recognition using wearable sensors has become essential for a variety of applications. Tri-axial accelerometers are the most widely used sensor for activity recognition. Although various features have been used to capture patterns and classify the accelerometer signals to recognise activities, there is no consensus on the best features to choose. Reducing the number of features can reduce the computational cost and complexity and enhance the performance of the classifiers. This paper identifies the signal features that have significant discriminative power between different human activities. It also investigates the effect of sensor placement location, the sampling frequency, and activity complexity on the selected features. A comprehensive list of 193 signal features has been extracted from accelerometer signals of four publicly available datasets, including features that have never been used before for activity recognition. Feature significance was measured using the Joint Mutual Information Maximisation (JMIM) method. Common significant features among all the datasets were identified. The results show that the sensor placement location does not significantly affect recognition performance, nor does it affect the significant sub-set of features. The results also showed that with high sampling frequency, features related to signal repeatability and regularity show high discriminative power.

The response of mangrove (Avicennia marina) seedlings to treated (wet) sludge from a sewage treatment plant (STP) was tested in a randomized block design experiment at a tree nursery on Mubarraz Island in the Arabian Gulf. The growth response of seedlings to half-strength and full-strength STP sludge was monitored over 103 days and compared with the response to freshwater, seawater and half-strength seawater treatments. Sludge treatments resulted in significantly greater plant growth, leaf number, leaf biomass and root biomass than the other treatments did. The positive effect of STP sludge on seedling growth is attributed to enhanced levels of total nitrogen (8.9 ± 0.1 mg l -1 ) and total phosphorus (7.8 ± 0.2 mg l -1 ) in the sludge and its low salinity. These results suggest that sludge from sewage treatment plants may be beneficially used in mangrove nurseries and plantations in this arid region, where soils are nutrient-poor and fresh water is scarce., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Eyewitnesses to crimes sometimes search for a culprit on social media before viewing a police lineup, but it is not known whether this affects subsequent lineup identification accuracy. The present online study was conducted to address this. Two hundred and eighty-five participants viewed a mock crime video, and after a 15-20 min delay either (i) viewed a mock social media site including the culprit, (ii) viewed a mock social media site including a lookalike, or (iii) completed a filler task. A week later, participants made an identification from a photo lineup. It was predicted that searching for a culprit on social media containing the lookalike (rather than the culprit) would reduce lineup identification accuracy. There was a significant association between social media exposure and lineup accuracy for the Target Present lineup (30% more of the participants who saw the lookalike on social media failed to positively identify the culprit than participants in the other conditions), but for the Target Absent lineup (which also included the lookalike) there was no significant association with lineup identification accuracy. The results suggest that if an eyewitness sees a lookalike (where they are expecting to see the culprit) when conducting a self-directed search on social media, they are less likely to subsequently identify the culprit in the formal ID procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elphick, Philpot, Zhang, Stuart, Pike, Strathie, Havard, Walkington, Frumkin, Levine, Price, Bandara and Nuseibeh.)

The E3 ubiquitin ligase Rad18 promotes a damage-tolerant and error-prone mode of DNA replication termed trans-lesion synthesis that is pathologically activated in cancer. However, the impact of vertebrate Rad18 on cancer genomes is not known. To determine how Rad18 affects mutagenesis in vivo , we have developed and implemented a novel computational pipeline to analyze genomes of carcinogen (7, 12-Dimethylbenz[a]anthracene, DMBA)-induced skin tumors from Rad18 +/+ and Rad18 - / - mice. We show that Rad18 mediates specific mutational signatures characterized by high levels of A(T)>T(A) single nucleotide variations (SNVs). In Rad18 - /- tumors, an alternative mutation pattern arises, which is characterized by increased numbers of deletions >4 bp. Comparison with annotated human mutational signatures shows that COSMIC signature 22 predominates in Rad18 +/+ tumors whereas Rad18 - / - tumors are characterized by increased contribution of COSMIC signature 3 (a hallmark of BRCA-mutant tumors). Analysis of The Cancer Genome Atlas shows that RAD18 expression is strongly associated with high SNV burdens, suggesting RAD18 also promotes mutagenesis in human cancers. Taken together, our results show Rad18 promotes mutagenesis in vivo , modulates DNA repair pathway choice in neoplastic cells, and mediates specific mutational signatures that are present in human tumors., (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.)

Background: Stress echocardiography is a well-established diagnostic tool for suspected coronary artery disease (CAD). Cardiovascular risk factors are used in the assessment of the probability of CAD. The link between the outcome of stress echocardiography and patients' variables including risk factors, current medication, and anthropometric variables has not been widely investigated., Objective: This study aimed to use machine learning to predict significant CAD defined by positive stress echocardiography results in patients with chest pain based on anthropometrics, cardiovascular risk factors, and medication as variables. This could allow clinical prioritization of patients with likely prediction of CAD, thus saving clinician time and improving outcomes., Methods: A machine learning framework was proposed to automate the prediction of stress echocardiography results. The framework consisted of four stages: feature extraction, preprocessing, feature selection, and classification stage. A mutual information-based feature selection method was used to investigate the amount of information that each feature carried to define the positive outcome of stress echocardiography. Two classification algorithms, support vector machine (SVM) and random forest classifiers, have been deployed. Data from 529 patients were used to train and validate the framework. Patient mean age was 61 (SD 12) years. The data consists of anthropological data and cardiovascular risk factors such as gender, age, weight, family history, diabetes, smoking history, hypertension, hypercholesterolemia, prior diagnosis of CAD, and prescribed medications at the time of the test. There were 82 positive (abnormal) and 447 negative (normal) stress echocardiography results. The framework was evaluated using the whole dataset including cases with prior diagnosis of CAD. Five-fold cross-validation was used to validate the performance of the framework. We also investigated the model in the subset of patients with no prior CAD., Results: The feature selection methods showed that prior diagnosis of CAD, sex, and prescribed medications such as angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were the features that shared the most information about the outcome of stress echocardiography. SVM classifiers showed the best trade-off between sensitivity and specificity and was achieved with three features. Using only these three features, we achieved an accuracy of 67.63% with sensitivity and specificity 72.87% and 66.67% respectively. However, for patients with no prior diagnosis of CAD, only two features (sex and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use) were needed to achieve accuracy of 70.32% with sensitivity and specificity at 70.24%., Conclusions: This study shows that machine learning can predict the outcome of stress echocardiography based on only a few features: patient prior cardiac history, gender, and prescribed medication. Further research recruiting higher number of patients who underwent stress echocardiography could further improve the performance of the proposed algorithm with the potential of facilitating patient selection for early treatment/intervention avoiding unnecessary downstream testing., (©Mohamed Bennasar, Duncan Banks, Blaine A Price, Attila Kardos. Originally published in JMIR Cardio (http://cardio.jmir.org), 29.05.2020.)

Polymerase theta (Pol θ, gene name Polq) is a widely conserved DNA polymerase that mediates a microhomology-mediated, error-prone, double strand break (DSB) repair pathway, referred to as Theta Mediated End Joining (TMEJ). Cells with homologous recombination deficiency are reliant on TMEJ for DSB repair. It is unknown whether deficiencies in other components of the DNA damage response (DDR) also result in Pol θ addiction. Here we use a CRISPR genetic screen to uncover 140 Polq synthetic lethal (PolqSL) genes, the majority of which were previously unknown. Functional analyses indicate that Pol θ/TMEJ addiction is associated with increased levels of replication-associated DSBs, regardless of the initial source of damage. We further demonstrate that approximately 30% of TCGA breast cancers have genetic alterations in PolqSL genes and exhibit genomic scars of Pol θ/TMEJ hyperactivity, thereby substantially expanding the subset of human cancers for which Pol θ inhibition represents a promising therapeutic strategy.

Background: Genomic profiling of colorectal cancer aims to identify actionable somatic mutations but can also discover incidental germline findings., Objective: The purpose of this study was to report the detection of pathogenic germline variants that confer heritable cancer predisposition., Design: This was a retrospective study., Settings: The study was conducted at a tertiary-referral institution., Patients: Between 2012 and 2015, 1000 patients with advanced cancer underwent targeted exome sequencing of a 202-gene panel. The subgroup of 151 patients with advanced colorectal cancer who underwent matched tumor-normal (blood) sequencing formed our study cohort., Interventions: Germline variants in 46 genes associated with hereditary cancer predisposition were classified according to a defined algorithm based on in silico predictions of pathogenicity. Patients with presumed pathogenic variants were examined for type of mutation, as well as clinical, pedigree, and clinical genetic testing data., Main Outcome Measures: We measured detection of pathogenic germline variants., Results: A total of 1910 distinct germline variants were observed in 151 patients. After filtering, 15 pathogenic germline variants (9.9%) were found in 15 patients, arising from 9 genes of varying penetrance for colorectal cancer (APC (n = 2; 13%), ATM (n = 1; 6%), BRCA1 (n = 2; 13%), CDH1 (n = 2; 13%), CHEK2 (n = 4; 27%), MSH2 (n = 1; 7%), MSH6 (n = 1; 7%), NF2 (n = 1; 7%), and TP53 (n = 1; 7%)). Patients with pathogenic variants were diagnosed at a younger age than those without (median, 45 vs 52 y; p = 0.03). Of the 15 patients, 7 patients (46.7%) with variants in low/moderate- penetrant genes for colorectal cancer would likely have not been tested based on clinical and pedigree criteria, where 2 harbored clinically actionable variants (CDH1 and NF2, 28.5% of 7)., Limitations: This study was limited by its small sample size and advanced-stage patients., Conclusions: Tumor-normal sequencing can incidentally discover clinically unsuspected germline variants that confer cancer predisposition in 9.9% of patients with advanced colorectal cancer. Precision medicine should integrate clinical cancer genetics to inform and interpret the actionability of germline variants and to provide follow-up care to mutation carriers. See Video Abstract at http://links.lww.com/DCR/A906.

Background: The recent proliferation of self-tracking technologies has allowed individuals to generate significant quantities of data about their lifestyle. These data can be used to support health interventions and monitor outcomes. However, these data are often stored and processed by vendors who have commercial motivations, and thus, they may not be treated with the sensitivity with which other medical data are treated. As sensors and apps that enable self-tracking continue to become more sophisticated, the privacy implications become more severe in turn. However, methods for systematically identifying privacy issues in such apps are currently lacking., Objective: The objective of our study was to understand how current mass-market apps perform with respect to privacy. We did this by introducing a set of heuristics for evaluating privacy characteristics of self-tracking services., Methods: Using our heuristics, we conducted an analysis of 64 popular self-tracking services to determine the extent to which the services satisfy various dimensions of privacy. We then used descriptive statistics and statistical models to explore whether any particular categories of an app perform better than others in terms of privacy., Results: We found that the majority of services examined failed to provide users with full access to their own data, did not acquire sufficient consent for the use of the data, or inadequately extended controls over disclosures to third parties. Furthermore, the type of app, in terms of the category of data collected, was not a useful predictor of its privacy. However, we found that apps that collected health-related data (eg, exercise and weight) performed worse for privacy than those designed for other types of self-tracking., Conclusions: Our study draws attention to the poor performance of current self-tracking technologies in terms of privacy, motivating the need for standards that can ensure that future self-tracking apps are stronger with respect to upholding users' privacy. Our heuristic evaluation method supports the retrospective evaluation of privacy in self-tracking apps and can be used as a prescriptive framework to achieve privacy-by-design in future apps., (©Luke Hutton, Blaine A Price, Ryan Kelly, Ciaran McCormick, Arosha K Bandara, Tally Hatzakis, Maureen Meadows, Bashar Nuseibeh. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 22.10.2018.)

Aims To report on great saphenous vein diameter distribution of patients undergoing endovenous laser ablation for lower limb varicose veins and the ablation technique for large diameter veins. Methods We collected retrospective data of 1929 (943 left leg and 986 right leg) clinically incompetent great saphenous vein diameters treated with endovenous laser ablation over five years and six months. The technical success of procedure, complications and occlusion rate at short-term follow-up are reported. Upon compression, larger diameter veins may constrict asymmetrically rather than concentrically around the laser fibre (the 'smile sign'), requiring multiple passes of the laser into each dilated segment to achieve complete ablation. Results Of 1929 great saphenous veins, 334 (17.31%) had a diameter equal to or over 15 mm, which has been recommended as the upper limit for endovenous laser ablation by some clinicians. All were successfully treated and occluded upon short-term follow-up. Conclusion We suggest that incompetent great saphenous veins that need treatment can always be treated with endovenous laser ablation, and open surgery should never be recommended on vein diameter alone.

Background Pelvic venous reflux is often treated with pelvic vein embolisation; however, atypical pelvic venous anatomy may provide therapeutic challenges. Methods We retrospectively reviewed seven patient files and reported symptoms, diagnostic imaging, aberrant anatomy and means by which the interventional radiologist successfully completed the procedure. Any follow-up data were included if available. Results Four anatomical abnormalities were found: internal iliac veins draining into the contralateral common iliac vein, duplicated inferior vena cava, reverse-angle renal veins with atypical left ovarian vein drainage and direct drainage of the internal iliac vein to the inferior vena cava. All patients were successfully treated with pelvic vein embolisation. Conclusion Abnormal embryologic development may cause variable pelvic venous anatomy. Knowledge of this will enable interventional radiologists to successfully treat such patients.

Introduction: Definitive treatment of localised colorectal cancer involves surgical resection of the primary tumour. Short-stay colectomies (eg, 23-hours) would have important implications for optimising the efficiency of inpatient care with reduced resource utilisation while improving the overall recovery experience with earlier return to normalcy. It could permit surgical treatment of colorectal cancer in a wider variety of settings, including hospital-based ambulatory surgery environments. While a few studies have shown that discharge within the first 24 hours after minimally invasive colectomy is possible, the safety, feasibility and patient acceptability of a protocol for short-stay colectomy for colorectal cancer have not previously been evaluated in a prospective randomised study. Moreover, given the potential for some patients to experience a delay in recovery of bowel function after colectomy, close outpatient monitoring may be necessary to ensure safe implementation., Methods and Analysis: In order to address this gap, we propose a prospective randomised trial of accelerated enhanced Recover y following M inimally I nvasive colorectal cancer surgery ( RecoverMI ) that leverages the combination of minimally invasive surgery with enhanced recovery protocols and early coordinated outpatient remote televideo conferencing technology ( TeleRecovery ) to improve postoperative patien-provider communication, enhance postoperative treatment navigation and optimise postdischarge care. We hypothesise that RecoverMI can be safely incorporated into multidisciplinary practice to improve patient outcomes and reduce the overall 30-day duration of hospitalisation while preserving the quality of the patient experience. ETHICS AND DISSEMINATION: RecoverMI has received institutional review board approval and funding from the American Society of Colorectal Surgeons (ASCRS; LPG103). Results from RecoverMI will be published in a peer-reviewed publication and be used to inform a multisite trial., Trial Registration Number: NCT02613728; Pre-results., Competing Interests: Competing interests: TeleRecovery is facilitated by the exceptional service of our midlevel providers, Kelly R. Maldonado , Brianna L. Whitener, Shanae L Ivey and Erika L Schlette. This study protocol and any subsequent manuscripts will be presented in accordance with the SPIRIT guidelines., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: There is increasing interest in nonoperative management (NOM) for rectal cancer with complete clinical response (cCR) after neoadjuvant chemoradiation (nCRT)., Objective: The aim of this systematic review was to summarize the available data on NOM, with the intention of formulating standardized protocols on which to base future investigations., Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. A highly sensitive literature search identified all relevant studies published between January 2004 and December 2016. Data extraction and quality assessment was performed independently by two authors, and resolved by consensus with a third reviewer., Results: In total, 15 studies, including 920 patients, met the inclusion criteria; 575 (62.5%) of these patients underwent NOM after cCR, with the remaining patients forming a surgical control group. The weighted mean follow-up was 39.4 (12.7) months in the NOM group and 39.8 (5.1) months in the surgery group. The pooled regrowth rate in the NOM group was 21.3% at a mean of 15.6 (7.0) months. Surgical salvage was possible and was undertaken in 93.2% of these patients. Overall survival in the NOM group was 91.7%, while disease-free survival was 82.7%. For the comparison proctectomy group, pooled rates of local recurrence, overall survival, and disease-free survival were 8.4, 92.4, and 87.5%, respectively., Conclusion: NOM may be a feasible option for surgically eligible rectal cancer patients with cCR after nCRT. Before such a strategy can be widely implemented, further prospective data are required with standardized definitions, diagnostic criteria, and management protocols, with an emphasis on shared patient-provider decision making and patient-centered outcomes.

Objective: We have previously reported strip-tract revascularization 1 year following high saphenous ligation and inversion stripping. This study reports the 5-8 year results in the same cohort., Methods: Between 2000 and 2003, 72 patients presented with primary varicose veins and had undergone high saphenous ligation and inversion stripping plus phlebectomies with or without subfascial endoscopic perforator surgery. Of the 64 patients who had attended for follow-up at 1 year, 35 patients (male:female, 16:19; 39 legs) underwent duplex ultrasonography 5-8 years after surgery (response rate 55%). Duplex ultrasonography was performed and all strip-tract revascularization and reflux and groin neovascularization was documented., Results: Eighty-two percent of legs of patients showed some evidence of strip-tract revascularization and reflux. Full and partial strip-tract revascularization and reflux was seen in 12.8% and 59% of limbs of patients, respectively, and 10.2% limbs of patients had neovascularization only at the saphenofemoral junction only. Seven limbs of patients showed no revascularization., Conclusion: Five to eight years after high saphenous tie and stripping, 82% of legs of patients showed some strip-tract revascularization and reflux and 12% showed total revascularization and reflux of the stripped great saphenous vein., (© The Author(s) 2014.)

For sensitive detection of rare gene repair events in terminally differentiated photoreceptors, we generated a knockin mouse model by replacing one mouse rhodopsin allele with a form of the human rhodopsin gene that causes a severe, early-onset form of retinitis pigmentosa. The human gene contains a premature stop codon at position 344 (Q344X), cDNA encoding the enhanced green fluorescent protein (EGFP) at its 3' end, and a modified 5' untranslated region to reduce translation rate so that the mutant protein does not induce retinal degeneration. Mutations that eliminate the stop codon express a human rhodopsin-EGFP fusion protein (hRho-GFP), which can be readily detected by fluorescence microscopy. Spontaneous mutations were observed at a frequency of about one per retina; in every case, they gave rise to single fluorescent rod cells, indicating that each mutation occurred during or after the last mitotic division. Additionally, the number of fluorescent rods did not increase with age, suggesting that the rhodopsin gene in mature rod cells is less sensitive to mutation than it is in developing rods. Thus, there is a brief developmental window, coinciding with the transcriptional activation of the rhodopsin locus, in which somatic mutations of the rhodopsin gene abruptly begin to appear.

Objectives: This is a retrospective study over 12 years reporting the healing rates of leg ulcers at a specialist vein unit. All patients presented with active chronic venous leg ulcers (clinical,aetiological, anatomical and pathological elements [CEAP]: C6) and had previously been advised elsewhere that their ulcers were amenable to conservative measures only., Method: Seventy-two patients (84 limbs) were treated between March 1999 and June 2011. Patients were contacted in August 2011 by questionnaire and telephone. Of 72 patients,two were deceased and two had moved location at follow-up, so were not contactable. Fifty patients replied and 18 did not (response rate 74%), representing a mean follow-uptime of 3.1 years., Results: Ulcer healing occurred in 85% (44 of 52 limbs) of which 52% (27) limbs were no longer confined to compression. Clinical improvement was achieved in 98% of limbs., Conclusions: This study shows that a significant proportion of ulcers currently managed conservatively can be healed by surgical intervention.

Two outstanding unknowns in the biology of photoreceptors are the molecular determinants of cell size, which is remarkably uniform among mammalian species, and the mechanisms of rod cell death associated with inherited neurodegenerative blinding diseases such as retinitis pigmentosa. We have addressed both questions by performing an in vivo titration with rhodopsin gene copies in genetically engineered mice that express only normal rhodopsin or an autosomal dominant allele, encoding rhodopsin with a disease-causing P23H substitution. The results reveal that the volume of the rod outer segment is proportional to rhodopsin gene expression; that P23H-rhodopsin, the most common rhodopsin gene disease allele, causes cell death via a dominant-negative mechanism; and that long term survival of rod cells carrying P23H-rhodopsin can be achieved by increasing the levels of wild type rhodopsin. These results point to promising directions in gene therapy for autosomal dominant neurodegenerative diseases caused by dominant-negative mutations.

Purpose: To engineer a knockin mouse model that can be used to monitor the effects of treatments on degradation and mislocalization of proline-to-histidine change at codon 23 (P23H) rhodopsin, a common cause of autosomal dominant retinitis pigmentosa (ADRP). The goal was to introduce a gene that expressed rhodopsin at low levels to avoid rapid retinal degeneration, and with a readily visible tag to make it easy to distinguish from wild type rhodopsin., Methods: One copy of the endogenous mouse rhodopsin gene was replaced with a mutant human rhodopsin gene that encodes P23H-rhodopsin fused to enhanced green fluorescent protein (GFP) at its C terminus. The gene includes a LoxP site in the sequence corresponding to the 5'-untranslated region, which greatly reduces translation efficiency. Characterized are the resulting heterozygous and homozygous P23H-hRho-GFP mouse lines for mRNA and protein expression, P23H-rhodopsin localization in rod cells, effects on visual function, and retinal degeneration., Results: The retinas of heterozygous P23H-hRho-GFP mice are morphologically and functionally very similar to those of wild type mice, and they display little cell death over time. P23H-hRho-GFP mice transcribe the knockin gene as efficiently as the endogenous mouse allele, but they contain much less of the protein product than do knockin mice expressing nonmutant hRho-GFP, indicating that substantial degradation of P23H-rRho-GFP occurs in mouse rod cells. The remaining P23H-hRho-GFP mislocalizes to the inner segment and outer nuclear layer, with only approximately 20% in rod outer segments., Conclusions: P23H-hRho-GFP mice provide a valuable tool for evaluating the efficacy of potential therapies for ADRP that influence the levels or localization of P23H-rhodopsin.

Introduction: Deep vein thrombosis (DVT) after varicose vein surgery is well recognised. Less well documented is endovenous heat-induced thrombosis (EHIT), thrombus extension into a deep vein after superficial venous thermoablation. We examined the rates of DVT in our unit after radiofrequency (RFA) and endovenous laser ablation (EVLA) with specific attention to thrombus type., Method: Retrospective analysis of all cases of RFA under general anaesthesia and EVLA under local anaesthesia was performed. Cases of DVT were identified from the unit database and analysed for procedural details., Results: In total, 2470 cases of RFA and 350 of EVLA were performed. Post-RFA, DVT was identified in 17 limbs (0.7%); 4 were EHIT (0.2%). Concomitant small saphenous vein (SSV) ligation and stripping was a risk factor for calf-DVT (OR 3.4, 95%CI 1.2-9.7, P=0.036), possibly due to an older patient group with more severe disease. Post-EVLA, 4 DVTs were identified (1%), of which 3 were EHIT (0.9%)., Conclusion: The DVT rate including EHIT was similar in patients treated with RFA and EVLA and was low. Routine post-operative duplex ultrasound scanning is recommended until the significance of EHIT is better understood, in accordance with consensus guidelines. DVT rates for both techniques compare favourably with those published for saphenous vein stripping., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Early success treating incompetent perforator veins (IPVs) with radiofrequency ablation (RFA) and the trend to move varicose vein surgery into a walk-in walk-out service led to the design of a specific device enabling RFA of IPVs using local anaesthesia (ClosureRFS stylet). Our aim was to assess one-year outcomes of a clinical series of patients undergoing treatment with this device. Truncal reflux, where present, was treated initially, and RFA of IPVs was performed as a secondary procedure., Method: Duplex ultrasound examinations were performed and the presence of IPVs documented. Results were compared with preoperative scans. IPVs were classified as closed, not closed/reopened or de novo., Results: Of the 75 patients invited for follow-up, 53 attended at a median time of 14 months (range 11-25). Sixty-seven limbs were analysed (M:F 1:2.1, median age 62, range 25-81). Of the 124 treated IPVs, 101 were closed (82%). Clinical, aetiological, anatomical and pathological clinical score was improved in 49.3% limbs. IPV closure was reduced in patients with recurrent varicose veins compared with primary varicose veins (72.3% versus 87%, P = 0.056)., Conclusion: These results demonstrate the radiofrequency stylet device to be an effective treatment for IPVs.

The unintended bycatch of long-lived marine species in fishing gear is an important global conservation issue. One suite of management approaches used to address this problem restricts or modifies fishing practices in areas where the probability of bycatch is believed to be high. Information on the distribution and behavior of the bycaught species is a desirable component of any such scheme, but such observations are often lacking. We describe a spatially explicit approach that combines data on the distribution of fishing effort and observations of the distribution of bycatch species derived from satellite telemetry. In a case study, we used a spatially explicit predator-prey model to investigate real-time interactions between three species of sea turtles (Caretta caretta, Chelonia mydas, and Lepidochelys kempii) and the fall large-mesh gill net fishery that targets southern flounder (Paralichthys lethostigma) in Pamlico Sound, North Carolina between 2002 and 2004. The model calculates a spatial overlap index, thereby allowing us to identify which fishing areas have the greatest risk of encountering bycatch. In this study, our telemetry deployments (n = 50) were designed specifically to address existing fisheries conservation measures in Pamlico Sound intended to reduce sea turtle bycatch. We were able to predict the spatial distribution of bycatch and evaluate management measures. This approach offers a powerful tool to managers faced with the need to reduce bycatch.

Objectives: Mounting evidence suggests that pelvic vein reflux is an important contributing factor to recurrent varicose veins. We compared the incidence in our specialist private unit (Unit A) with that of a District General Hospital (Unit B)., Methods: Results of all female patient lower limb duplex ultrasound (LLDUS) and transvaginal pelvic ultrasound (TVUS) scans performed over a one-year period were retrospectively reviewed. Patients with refluxing veins emanating from the abdomen or pelvis on LLDUS (non-saphenous reflux) routinely proceeded to TVUS in Unit A., Results: In Unit A, non-saphenous reflux on LLDUS was present in 90-462 female patients (19.5%). In 81.1% of these, TVUS confirmed reflux in truncal pelvic veins (incidence 15.8%). In Unit B, non-saphenous reflux was present in 60-279 female patients (21.5%)., Conclusion: One in five women presenting with varicose veins have reflux of non-saphenous origin. This is the case in specialist and non-specialist units. One in six has associated pelvic vein reflux.

Unlabelled: In 2000, we developed a percutaneous method of treating incompetent perforator veins (IPV) using ultrasound-guided radiofrequency ablation (RFA), which we termed TRansluminal Occlusion of Perforator (TRLOP)., Objective: To audit the five-year outcome of the TRLOP technique as indicated by the rate of IPV closure on duplex ultrasound (DUS)., Methods: Patients underwent DUS five years post-TRLOP. Experienced vascular technologists documented the presence of IPVs using a two co-ordinate system, blinded to previous results. Results were then compared with preoperative scans. IPVs were classified as: closed; not closed/reopened; or de novo. Closed IPVs were defined as the absence of any IPV at or within 5 cm of a previous IPV in the vertical and horizontal plane. Any IPVs found outside the delineated area were defined as de novo IPVs., Results: Of 67 patients invited, 37 attended DUS (55% participation rate; men to women ratio of 14:23, age 40-84; mean 64). Preoperative clinical, aetiological, anatomical and pathological classification: C2, 36.2%; C3, 27.6%; C4, 34.5%; C6, 1.7%. From 125 IPVs analysed, 101 were closed (81%), 24 were not closed/reopened (19%) and 14 de novo IPVs were found., Discussion: Despite these results representing our learning curve for the procedure, we found TRLOP to be an effective treatment for IPVs. The closure rates described are comparable with the published clinical series data for subfascial endoscopic perforator surgery.

Aim: End-stage renal disease (ESRD) is often complicated by chronic inflammation and malnutrition. We tested whether serum tartrate-resistant acid phosphatase (TRACP) isoform 5a relates to other markers of inflammation in ESRD., Material: Predialysis serum was collected from 99 ESRD patients (51 male, 48 female) aged 55 +/- 15 years and a control group of 36 healthy subjects (8 male, 28 female) aged 43.2 +/- 10.5 years., Methods: Serum TRACP 5a activity and protein, TRACP 5b activity and C-reactive protein (CRP) were estimated by in-house immunoassays. Commercial kits were used for serum bone-specific alkaline phosphatase, Ntelopeptides of Type I collagen, interleukin-6 (IL-6) and fetuin-A. Intact parathyroid hormone was determined by chemiluminescent assay. Albumin, cholesterol, triglycerides, ferritin and hemoglobin were compared to the hospital reference ranges. Bone mineral density (BMD) was measured at the heel in 69 patients and all control subjects and expressed as g/cm2 and age-corrected T-score., Results: Mean (median) levels of all serum markers were significantly elevated in ESRD except fetuin-A, which was significantly reduced. Mean BMD (g/cm2) was not different than control, but mean T-score was significantly reduced. TRACP 5a protein correlated with CRP, triglycerides and ferritin, but not with IL-6 or any other nutritional or bone markers or BMD. TRACP 5b activity correlated with all bone markers and BMD, but not with inflammation or nutritional markers., Conclusion: Our findings suggest that TRACP 5a may be a useful marker to estimate the degree of inflammation in ESRD patients on chronic hemodialysis.

Aims: To establish a possible mechanism of damage to a laser fibre significant enough to cause a retained segment within a patient., Methods: A 21 G needle was used to pierce a VARILASE 810 nm Laser Fibre inserted within a 4F sheath. A tiny pin source of light from the aiming beam emerged from the needle hole in the sheath. Using laser protection protocol, the generator was fired for one minute at 14 Watts (W) continuous wave. The sheath and fibre were then examined. In a control experiment, we were unable manually to break a fibre where the coating had been damaged prior to the laser being fired., Results: The aiming beam was noted to be concentrated at the side of the catheter at the point of needle damage rather than at the fibre tip. When the fibre was removed from the sheath the distal length, from the point of damage to the tip, was retained within the sheath. Longer firing with the sheath surrounded by a wet towel or a pork loin resulted in complete severance of the sheath and fibre., Conclusion: There are no firm manufacturer's guidelines on whether Tumescent Anaesthesia should be delivered before or after the laser fibre has been inserted into the patient. Some units performing EVLA prefer to do this with the laser fibre in situ as it is easier to image on ultrasound than the sheath alone. The results of this in-vitro experiment would suggest it is possible to cause sufficient needle damage to fracture a laser fibre when fired. In the interests of safety we would recommend administration of tumescent anaesthesia should always be carried out before introduction of the laser fibre.

Pelvic venous embolization is performed for pelvic congestion syndrome and prior to lower limb varicose vein surgery in females with associated pelvic venous insufficiency. The procedure is analogous to varicocele embolization in males, although refluxing internal iliac vein tributaries may also be embolized. We report a case of inadvertent coil placement in the common femoral vein while embolizing the obturator vein, during pelvic vein embolization for recurrent lower limb varicose veins. There were no clinical consequences and the coil was left in situ. We advise caution when embolizing internal iliac vein tributaries where there is clinically significant communication with veins of the lower limb.

Trinucleotide repeat instability is intrinsic to a family of human neurodegenerative diseases. The mechanism leading to repeat length variation is unclear. We previously showed that treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) dramatically increases triplet repeat instability in mammalian cells. Based on previous reports that demethylation increases homologous recombination (HR), and our own observations that HR destabilizes triplet repeats, we hypothesized that demethylation alters repeat stability by stimulating HR. Here, we test that hypothesis at the adenosine phosphoribosyl transferase (Aprt) locus in CHO cells, where CpG demethylation and HR have both been shown to increase CAG repeat instability. We find that the rate of HR at the Aprt locus is not altered by demethylation. The spectrum of recombinants, however, was shifted from the usual 6:1 ratio of conversions to crossovers to more equal proportions in 5-aza-CdR-treated cells. The subtle influences of demethylation on HR at the Aprt locus are not sufficient to account for its dramatic effects on repeat instability. We conclude that 5-aza-CdR promotes triplet repeat instability independently of HR.

The scleraxis (Scx) gene, encoding a bHLH transcription factor, is expressed in the progenitors and cells of all tendon tissues. To determine Scx function, we produced a mutant null allele. Scx-/- mice were viable, but showed severe tendon defects, which manifested in a drastically limited use of all paws and back muscles and a complete inability to move the tail. Interestingly, although the differentiation of all force-transmitting and intermuscular tendons was disrupted, other categories of tendons, the function of which is mainly to anchor muscles to the skeleton, were less affected and remained functional, enabling the viability of Scx-/- mutants. The force-transmitting tendons of the limbs and tail varied in the severity to which they were affected, ranging from dramatic failure of progenitor differentiation resulting in the loss of segments or complete tendons, to the formation of small and poorly organized tendons. Tendon progenitors appeared normal in Scx-/- embryos and a phenotype resulting from a failure in the condensation of tendon progenitors to give rise to distinct tendons was first detected at embryonic day (E)13.5. In the tendons that persisted in Scx-/- mutants, we found a reduced and less organized tendon matrix and disorganization at the cellular level that led to intermixing of tenocytes and endotenon cells. The phenotype of Scx-/- mutants emphasizes the diversity of tendon tissues and represents the first molecular insight into the important process of tendon differentiation.

Background: Varicose veins that recur after standard high tie and strip are often associated with venous reflux in the thigh, as shown by duplex ultrasonography. The aim of this study was to look for evidence of revascularization in the strip track after great saphenous vein (GSV) stripping., Methods: A consecutive series of patients with duplex-proven great saphenous varicose veins underwent saphenofemoral ligation with intraoperative confirmation of successful stripping. Duplex ultrasonography was performed 1 week and 1 year after surgery. The presence and extent of haematoma was noted, as was any venous reflux within the strip track., Results: At 1 year, four (6 per cent) of 70 patients had complete revascularization of the strip track and 12 (17 per cent) had partial revascularization, all with duplex-proven reflux. Partial revascularization was in the distal third of the track in six legs (9 per cent of the 70 patients), in the distal half in five (7 per cent) and was almost complete in one leg (1 per cent). All patients with revascularization had a significant strip-track haematoma at 1 week after surgery., Conclusion: Revascularization of the GSV strip track after stripping was found in 23 per cent of patients after 1 year; all of these had a postoperative haematoma in the track., (Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

We report the case of a 19 year old man who received a gunshot wound to the soft tissues of his left elbow. He presented with an ischaemic hand due to transection of the brachial artery bifurcation anterior to the elbow joint. He was spared an associated median nerve injury by an anomalous course of the nerve through the antecubital fossa.

Interventional radiology has resulted in a reduced need for bypass procedures for aorto-occlusive disease. However, there are still indications for surgery of this type, which carries with it a small but significant morbidity and mortality. False aneurysms are well described following such procedures but with the development of inert, strong and non-absorbable materials they are becoming less common. This paper describes the acute presentation of a false aneurysm of the aorta following an aorto-iliac bypass where true aneurysmal change had taken place in the area of the anastomosis.

Surgical attention to major blood vessels has been necessary for as long as man has been involved in armed combat. A brief resume of the history of vascular surgery is outlined with special reference to the contribution made by the military surgeon in battle. The role of modern specialist techniques in vascular injuries in present day operations will be briefly discussed.

There are many different antennal morphologies for insects, yet they all have the same functional role in olfaction. Chemical signals are dispersed through two physical forces; diffusion and fluid flow. The interaction between antennal morphology and fluid flow generates a region of changing flow velocity called the boundary layer. The boundary layer determines signal dispersion dynamics and therefore influences the signal structure and information that arrives at the receptor cells. To investigate how the boundary layer changes the information in the signals arriving at receptor cells, we measured chemical dynamics within the boundary layer around the bee antennae using microelectrodes. We used two types of chemical signals: pulsed and continuous. The results showed that the boundary layer increased the decay time of the chemical signal for the pulsatile stimuli and increased the peak height for the continuous data. Spectral analysis of continuous signals showed that the temporal aspects of the chemical signal are changed by the boundary layer. Particularly the temporal dynamics of the signal are dampened at the slowest flow speed and amplified at the intermediate and fast flow speeds. By altering the structure of the chemical signal, the morphology will function as a sensory filter.

An overgrowth of pathogenic organisms occurs following rat heterotopic small bowel transplantation. This study assessed whether the bacterial microflora return to normal following subsequent orthotopic transposition of the graft. After 14 days the heterotopic graft was placed into continuity following resection of 15 cm of the host midintestinal loop. Quantitative and qualitative analyses of the intraluminal bacteria were performed studying the resected host intestine, the heterotopic graft at 14 days, and the graft 14 days after transposition. A group of normal rats were used as controls. An overgrowth of Staphylococcus epidermidis evident in the heterotopic graft at 14 days returned to a more normal bacterial profile following orthotopic transposition. These findings suggest that early interposition of a small bowel graft into an orthotopic position may prevent an alteration in the small bowel ecology toward potentially pathogenic organisms capable of translocation.