bluuebunny/crossref_metadata_2025 huggingface dataset:
O59: USE OF DEXTRAN 40 FOLLOWING PANCREAS TRANSPLANT MAY REDUCE EARLY INFLAMMATION AND SIGNIFICANT BLEEDING COMPARED TO A HEPARIN-BASED PROTOCOL
Authors: Innes AH , Tingle SJ , Ibrahim I , Thompson E , Bates L , Manas D , White S , Wilson C
Published: April 2021

Introduction

Dextran 40 (D40) is a synthetic colloid with anticoagulant properties, which is commonly used instead of heparin following pancreas transplantation, however there is a lack of evidence over which is more effective. Graft thrombosis and pancreatitis, which may be mediated through micro or macrothrombosis within the graft, remain significant complications following pancreas transplantation. We hypothesised that D40 reduces inflammation through its antithrombotic pro-microcirculatory effects. We aimed to evaluate D40 compared to a heparin-based protocol by comparing post-operative complications and post-transplant levels of inflammation.

Method

Data were collected retrospectively for pancreas transplant patients between December 2009 and August 2018 – 26 patients had been treated with the pre-Dextran protocol and 37 had received D40. Post-operative complications and inflammatory markers (WCC, CRP and amylase) on post-operative days 1, 2, 3 and 7 were compared between the two groups. Potential confounders were also recorded.

Result

Patients in the D40 group had similar thrombosis rates but were less likely to have had substantial post-operative bleeding compared to the heparin-based protocol. The group who received D40 had significantly lower CRP and WCC on days 2, 3 and 7. The differences on days 3 and 7 remained when the results were adjusted for the significant confounders - cold ischaemic time and donor age.

Conclusion

D40 appears to be as effective as IV heparin at preventing graft thrombosis following pancreas transplant, and to confer a reduced risk of bleeding. It may also reduce post-operative inflammatory processes, leading to reduced graft pancreatitis.

Take-home message

Using Dextran 40 as an anticoagulant after pancreas transplantation is as effective as IV heparin at preventing graft thromboses and has a reduced risk of bleeding.
O60: SURGICAL SITE INFECTION AND ANTIMICROBIAL RESISTANCE FOLLOWING RESECTION AND RECONSTRUCTIVE SURGERY FOR ORAL CANCERS: ARE WE READY FOR THE SUPER BUGS?
Authors: Ravindhran B , AM Hema , Vijaykumar M
Published: April 2021

Introduction

Surgical site infection(SSI) is the most common complication occurring in 19 to 47% of patients undergoing surgery for oral cancers. This study aims to assess the predictive factors of SSIs and antibiotic resistance patterns in patients undergoing surgery for oral cancers.

Method

The Clinico-pathological data of all patients who underwent surgery for oral cancers at our centre between October 2014 and May 2019 were reviewed. The differences between groups were compared by using independent samples t-test or Mann-Whitney U test and categorical data were analysed by Pearson's chi-square test, Fisher's exact or continuity correction. ROC curve was plotted to find the cut-off levels for the various predictors of SSI, using the Youden's index method. A linear regression analysis was done to define the cause-effect relationship of categorical response variables with explanatory variables.

Result

Of the 135 patients in our cohort, 43 patients(31.2%) developed SSI.Univariate and multivariate analysis showed that Diabetes, BMI>25 or <18, Neutrophil-to-Lymphocyte Ratio(NLR)>3.75, Platelet-to-Lymphocyte Ratio(PLR)>137.5, neo-adjuvant chemotherapy or radiotherapy, prolonged operative duration and prolonged anaesthesia exposure may render patients more vulnerable to SSI. On regression analysis, a PLR>137.5, NLR>3.75 and BMI>25 or <18 were found to be highly predictive of SSI. The highly resistant organisms isolated were staphylococcus aureus and enterococcus species.

Conclusion

The identification of these risk factors in patients undergoing surgery for oral cancers can help in identification of patients who may be at a higher risk of developing SSI and therefore help in improving the overall outcome, especially in an LMIC setting.

Take-home message

Identification of risk factors for surgical site infections in patients could help in prompt management of SSI and can also help in reduction of overall morbidity. The awareness and prevention of antibiotic resistance is vital for good outcomes in reconstructive surgery.
O64: GENOMIC PROFILING USING CIRCULATING NUCLEIC ACIDS IN STAGE IV MELANOMA PATIENTS RECEIVING IMMUNOTHERAPY REVEALS A NOVEL GENE AMPLIFICATION LANDSCAPE AND ALLOWS FOR DETECTION OF ACTIONABLE GENE MUTATIONS
Authors: Ita M , Wang JH , O'Leary P , Nolan Y , Toulouse A , Heffron C , Power D , Redmond HP
Published: April 2021

Introduction

Serial monitoring for disease progression and therapeutic efficacy at the molecular level in metastatic melanoma is hampered by a lack of reliable blood borne biomarkers. Molecular profiling of melanoma tumours is almost impractical in metastatic disease due to risks of procedure related morbidity and sampling inefficiency in representing tumour heterogeneity. Cell free DNA allows monitoring of molecular changes in melanoma over the course of immunotherapy. We investigated the utility of somatic mutation and gene amplification analyses in melanoma patients receiving immunotherapy.

Method

Cell free DNA was extracted from plasma using a QIAamp Circulating Nucleic Acid Kit (Qiagen). Pathway focused profiling of somatic mutation status was performed by ARMs PCR using QBiomarker Somatic Mutation PCR Arrays (Qiagen). Gene amplification analysis was performed by Real Time Quantitative PCR (Roche) using RT2 Profiler PCR Arrays (Qiagen).

Result

A total of twenty patients with stage IV melanoma receiving immunotherapy were enrolled in this study. The BRAF p.V600E mutation was detected in the cfDNA of 80% of BRAF positive patients. Cell free DNA was also profiled for a total of 84 genes of the cancer inflammation and immunity pathway. There was a significant difference in the copy numbers of several genes (CTLA-4, CXCL12, CXCL5, IDO1, TGFB, IFNG, IL4, PTGS2, AICDA, HLA-A, CCL4, ACKR3, TP53, MYC) between patients with progressive disease and therapeutic response (n=20, p < 0.05).

Conclusion

We postulate that cell free DNA pathway focused somatic mutation and gene amplification analyses may be useful in evaluating disease progression and therapeutic response.

Take-home message

Genomic analysis of circulating nucleic acids may be useful in evaluating disease progression and therapeutic response in metastatic melanoma.
O65: C-MET PROTEIN AS A COLORECTAL CANCER BIOMARKER FOR FLUORESCENCE IMAGE-GUIDED SURGERY
Authors: Armstrong G , Portal C , Khot MI , West NP , Maisey T , Perry S , Tolan D , Jayne DG
Published: April 2021

Introduction

The c-Met transmembrane protein is vital for cell differentiation and migration and is overexpressed in many gastrointestinal cancers. This study aimed to investigate a novel c-Met targeted peptide coupled to a fluorophore (EMI-137, Edinburgh Molecular Imaging Ltd.) for use in fluorescence image-guided colorectal cancer (CRC) surgery.

Method

A high c-Met expressing cell-line, HT29, was identified with temporary RNA suppression and used to develop a mouse xenograph CRC model. Tumours were allowed to grow to 10mm. EMI-137 was injected into the tail vein and biodistribution analysed using the IVIS system.

Nine patients undergoing elective surgery for colon cancer received a single IV dose EMI-137 1-3 hours before surgery. Tumour and LN fluorescence was assessed with a prototype Karl Storz laparoscope. Intraoperative fluorescence was correlated with radiological and pathological TNM stage and tissue c-Met expression using immunohistochemistry.

Result

The HT29 xenograph CRC model demonstrated selective EMI-137 uptake and fluorescence 1- 6 hours post administration. Nine participants aged 67-77 years received EMI-137 106 minutes (S.D±17) before surgery. Marked background fluorescence was observed in all patients. 4/9 (44%) patients showed mild increase in tumour fluorescence over background. 5/9 patients had histological LN disease, but no fluorescent nodes were detected intraoperatively. There was no correlation with T-stage. At histopathological assessment 8/9 participants showed moderate or high tumour c-Met expression. 8/8 malignant LNs demonstrated high c-Met expression.

Conclusion

EMI-137 is specific for human c-Met in 2D and xenograph CRC models. EMI-137 is safe for human use but its utility is limited by insufficient tumour-to-background ratios.

Take-home message

This first-in-man study of a novel fluorescent peptide targeted to the c-Met receptor, found EMI-137 lacked the sensitivity and specificity to accurately map the tumour margins and lymph node burden in laparoscopic colonic cancer resection surgery.
O67: PERFUSATE GLUCOSE REFLECTS TISSUE GLYCOGENATION DURING LIVER PERFUSION
Authors: Matthews L , Irwin E , Ezuma P , Ibrahim I , Bates L , Thompson E , Wright M , Figueiredo R , Bury Y , Wilson C
Published: April 2021

Introduction

Normothermic machine perfusion (NMP) is a method of organ preservation that aims to replicate the physiological environment, achieved by perfusing the livers with a blood-based perfusate at physiological inflow pressures and temperature. NMP also permits viability assessment through evaluation of the perfusate flow rates through the portal vein and hepatic artery. In addition to this, biochemical assessment and perfusate gas analysis can be performed to provide insights into the metabolic activity of the liver.

Method

Discarded human liver grafts (n=6), were perfused for 24 hours. Core biopsies and perfusate samples were taken from each liver at 5 distinct time intervals over 24 hours. Core biopsies were fixed and stained with periodic acid-Schiff and analysed with Leica software to provide a quantitative estimate of the hepatocellular glycogen content.

Result

Hepatic glycogen concentration rose during the first hour, followed by a steady decline thereafter until the end of perfusion. Contrary to our initial hypothesis that glucose concentration within the circuit would show an inverse relationship to glycogen stores in the liver cells, we found that glucose concentration closely followed the same trend.

Conclusion

Change in hepatocyte glycogen content provides an important insight into the synthetic function of a liver destined for transplant. Our research suggests that glucose concentration can be used as a surrogate marker for the synthetic function of a liver on NMP and provides valuable information on the glycogen-synthesising capability of the hepatocytes. In future, this could potentially aid the decision-making process with regards to liver graft transplant viability.

Take-home message

Perfusate glucose concentration could provide an insight into the viability of liver transplants
P10: LYMPH NODE YIELD IS NOT A RELIABLE PROGNOSTIC MARKER IN ANTERIOR RESECTION AND ABDOMINOPERINEAL RESECTION FOLLOWING NEOADJUVANT THERAPY FOR RECTAL CANCER
Authors: Harris J , Fleming CA , Ullah MF , McNamara E , Murphy S , Shelly M , Waldron D , Condon E , Coffey JC , Peirce CB
Published: April 2021

Introduction

International guidelines recommend a minimum lymph node yield (LNY) of ≥12 for oncological resection in colorectal cancer (CRC). Neoadjuvant chemoradiotherapy (NACRT) decreases LNY, which questions its ability to provide accurate prognostic information. The consensus of this significance remains undetermined. This study aimed to investigate the significance of LNY on recurrence and survival following anterior resection and abdominoperineal resection with or without NACRT for rectal cancer.

Method

Prospectively collected data on patients diagnosed with rectal cancer in a tertiary referral centre was interrogated retrospectively. Patients were divided into primary surgery and NACRT groups. Univariable analysis was performed using Fisher's exact test, t-test, and x2 test, while multivariable analysis utilised a multiple regression model. Disease recurrence and survival was analysed with logrank test for Kaplan-Meier curves.

Result

148 patients were included [56.1% (n=83) receiving NACRT]. The median LNY of the primary surgery group was 14 [interquartile range (IQR) 11-19] and for the NACRT group was 12 (IQR 8-14) (p <0.001). Disease recurrence was similar in both primary surgery and NACRT groups. There was a significant decrease in overall mortality in NACRT patients (p = 0.03), but there was no significant difference observed in recurrence or mortality amongst LNYs of <8, 8-11, and ≥12.

Conclusion

LNY less than 12 was not a negative prognostic indicator following NACRT and surgery for rectal cancer.

Take-home message

A lymph node yield of less than 12 is not a negative prognostic indicator in rectal cancer patients who receive neoadjuvant chemotherapy.
P16: PHYSICAL THERAPIES FOR DVT PROPHYLAXIS IN SURGICAL PATIENTS: A SYSTEMATIC REVIEW AND EVIDENCE QUALITY APPRAISAL
Authors: Berner JE , Geoghegan L , Kyriazidis I , Nanchahal J , Jain A
Published: April 2021

Introduction

Venous thromboembolism represents a significant clinical and socioeconomic burden. Surgical patients are an inherently high-risk cohort for VTE although traditional prophylactic pharmacological therapies are contraindicated in select cohorts. Novel physical therapies such as calf exercises and electrostimulation have been proposed for such patients. The aim of this systematic review is to appraise the clinical utility of novel physical therapies used for DVT prophylaxis in surgical and trauma patients.

Method

A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to July 2019 was conducted. Abstract screening and data extraction were performed in duplicate. Risk of bias and quality assessments were performed for each study using the GRADE framework.

Result

A total of 272 articles were identified, of which 10 met inclusion criteria. Five studies evaluated the use of calf electrostimulation, the remaining studies evaluated active toe movement, bespoke compression bandages, blood flow restriction exercises, calf massage and a portable compression device. Four randomized controlled trials demonstrated a significant reduction in radiological DVT incidence with electrostimulation, post-operative massage and pneumatic compression versus controls. All included studies had a moderate to high risk of bias.

Conclusion

The role of physical therapies as prophylactic measures in VTE remain equivocal. No study demonstrated a significant reduction in clinically evident DVT. The physical therapies can be beneficial in patients who also received pharmacological therapy, whilst physical therapies alone may be of no benefit. Heterogenous study design and poor methodological quality limit comparison of study findings at present.

Take-home message

Physical therapies as prophylactic measures in venous thromboembolism may offer benefit when combined with pharmacotherapy. When used alone, physical therapies may offer no benefit.
P29: TRANSVERSUS ABDOMINIS PLANE BLOCK IN LAPAROSCOPIC BARIATRIC SURGERY- A SYSTEMATIC REVIEW AND META ANALYSIS OF RANDOMISED CONTROLLED TRIALS
Authors: Aamir A , Sahebally SM , Heneghan HM
Published: April 2021

Introduction

Effective postoperative analgesia is paramount in the management of patients undergoing bariatric surgery, given their increased predisposition to systemic narcotic-induced respiratory depression. Transversus abdominis plane (TAP) block has shown promise in the enhanced recovery pathway for several abdominal procedures. We performed a systematic review and meta-analysis to compare the effectiveness of TAP block in laparoscopic bariatric surgery.

Method

PubMed, EMBASE and Cochrane databases were searched for relevant articles from inception until November 2019. All trials that compared TAP blocks versus none in laparoscopic bariatric procedures were included. The primary outcome measure was narcotic consumption at 24 hours postoperatively, while secondary outcomes included pain scores, time to ambulation, postoperative nausea and vomiting (PONV) and complication rates. Random effects models were used to calculate pooled effect size estimates.

Result

Seven randomised controlled trials were included capturing 617 patients. There was high statistical heterogeneity across studies. On random effects analysis, there were no significant differences in narcotic consumption (Mean difference –18.4 mg, 95% CI=-38.7 to 1.91, p=0.08), pain scores (Mean difference -0.71, 95% CI=-1.93 to 0.50, p=0.25) or complications (OR=0.67, 95% CI=0.11 to 4.23, p=0.67) between TAP and no TAP groups. However, TAP was associated with significantly less time to ambulation (Mean difference -2.22 hours, 95% CI=-3.89 to -0.56, p=0.009), and PONV (OR=0.13, 95% CI=0.05 to 0.35, p<0.0001) rates.

Conclusion

TAP in laparoscopic bariatric surgery is associated with significantly less PONV and time to ambulation but similar narcotic usage, postoperative pain and complication rates, compared to no TAP.

Take-home message

TAP in laparoscopic bariatric surgery is associated with a shorter time to ambulation and less PONV but similar postoperative pain and narcotic usage, compared to no TAP.
P30: PYY HORMONE UPREGULATES PROXIMAL GLP-1 RELEASE AFTER ROUX EN-Y GASTRIC BYPASS
Authors: Prada-Oliveira JA , Camacho-Ramirez A , Almorza-Gomar D , Ribelles-Garcia A , Carrasco-Molinillo MA , Pérez-Arana G.
Published: April 2021

Introduction

Nowadays Roux-en-Y gastric bypass (RYGB) has provided a powerful treatment for type 2 diabetes mellitus. Nevertheless how anatomical arrangements after RYGB influeces entero-hormonal response and the role of Peptide Tyrosine Tyrosine (PYY) in the restoration of normoglycaemia are still not clear. MATERIAL AND

Method

We demonstrate that PYY plasma levels showed a remarkable peak, around thirty minutes earlier than GLP-1 or GIP, after mixed-meal administration in non obese Goto – Kakizaki RYGB-operated rats . Also, we found that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal.

Result

Histologically the number of GLP-1 positive cells number appeared to increase in the three segments of the small intestine:duodenum jejunum and ileum in GK RYGB-operated rats beyond early presence of nutrient stimulation in the ileum. But nevertheless, PYY positive cell numbers appeared to increased only in the ileum.

Conclusion

Taking together this findings suggest an earlier central role for PYY in gut hormone regulation after RYGB in our model, contributing to GLP-1 and GIP release and support the existence of enteroendocrine communication routes between the distal and proximal small intestine.

Take-home message

Enterohormones release changes after bariatric surgery due to the consequences in nutrients flow. The GLP-1 release is increased and we report its related to the PYY regulation.
P34: PRINTABILITY & CYTOCOMPATIBILITY TESTING OF XANTHAN GUM FOR EXTRUSION-BASED 3D BIOPRINTING IN WOUND HEALING
Authors: Moura F , Malferrari S , Kalaskar D
Published: April 2021

Introduction

Bioprinting facilitates highly-specific deposition of skin cells and biomaterials. Skin bioprinting is still limited by prolonged printing processes, poor mechanical properties and incomplete complexities. An important barrier is identifying an ideal hydrogel for skin bioprinting – one with a good balance between printing viable cells and producing robust scaffolds. Herein, three hydrogels were tested for potential use as bio-inks.

Method

A pneumatic-extrusion Inkredible 3D bioprinter was used. Initially, different concentrations of Alginate (reference), XG and Alginate/XG mixture were quantitatively evaluated for printability by calculating aspect ratio, square printability and cylinder height. The best two printable concentrations of each hydrogel were selected to undergo hDF viability testing to assess the effect of the printing process (Nozzle diameter and viscosity). The best concentration for each hydrogel group with best cell viability then underwent a 14-day hDF cytocompatibility testing period by using Live/dead staining, metabolic activity, dsDNA and collagen quantification.

Result

XG revealed a remarkable ability to build 3D shapes (XG(6%) with 27G nozzle-10.0mm±0.2 cylinder height). XG(6%), Alginate/XG(4%/10%) and Alginate(6%) were identified as the best concentrations to undergo 14-day cytocompatibility testing. XG(6%) and Alginate/XG(4%/10%) had better day 1 hDF viability (87.3%±2.9; 87.6%±1.5, respectively) than Alginate(6%)(74%±2.65). All hydrogels had gradually improving cell viability. Cell proliferation remained comparable amongst all hydrogels. Moreover, collagen production was confirmed in all constructs.

Conclusion

Bioprinted XG is cytocompatible with hDF still further optimisation of XG is required to prolong its degradability to optimise its application as a hydrogel for skin bioprinting.

Abbrev

XG–Xanthan gum; hDF–human Dermal Fibroblasts

Take-home message

There is still no ideal hydrogel identified for the purpose of skin bioprinting. An updated systematic review should be carried out to assess the current best available hydrogels.
P37: THE IMPACT OF TEMPORAL ARTERY BIOPSY AT A UK TERTIARY PLASTIC SURGERY UNIT
Authors: Chew BJW , Khajuria A , Ibanez J
Published: April 2021

Introduction

Guidelines recommend temporal artery biopsy (TAB) for patients suspected of having giant cell arteritis (GCA). We evaluated the impact of TAB on the diagnosis and management of patients with suspected GCA at a tertiary plastic surgery unit.

Method

A retrospective review of all TAB procedures performed at our centre over 7 years was performed. One hundred and one patients were included in the study. Patients were classified into 3 diagnostic groups: confirmed (positive TAB), presumed (negative TAB with high clinical suspicion) and unlikely (negative TAB with low clinical suspicion). The clinical presentation and management for each group were compared.

Result

The average American College of Rheumatology (ACR) score was 3.07. The number of patients with an ACR score of ≥3 before TAB was 72 (71.3%) and remained the same after TAB. The number of patients who remained on steroid therapy was lower in the group with an unlikely diagnosis of GCA compared to the group with a confirmed diagnosis (p<0.05). Conversely, there was no significant difference in steroid therapy between those with a presumed and confirmed diagnosis (p>0.05).

Conclusion

This study found a significant difference in steroid treatment between those with confirmed GCA and those where the diagnosis was unlikely showing that TAB may support decisions regarding steroid therapy. However, TAB was inappropriately requested for patients whose pre-TAB ACR score was ≥3 as this score is sufficient for the diagnosis of GCA. Therefore, the use of TAB should be limited to cases of diagnostic uncertainty.

Take-home message

while temporal artery biopsy has a role to play in the diagnosis of GCA, its use should be limited to cases of diagnostic uncertainty and not requested for every patient with a suspicion of Giant Cell Arteritis.
Malassezia restricta:An Underdiagnosed Causative Agent of Blood Culture-Negative Infective Endocarditis
Authors: Houhamdi-Hammou Linda , Benito Yvonne , Boibieux André , Dupont Damien , Delahaye François , Thivolet-Bejui Françoise , Wallon Martine , Vandenesch François , Bouchiat Coralie
Published: April 2021

Background

Infective endocarditis (IE) is a severe disease requiring microbial identification to successfully adapt its treatment. Currently, identification of its etiological microorganism remains unresolved in 5.2% of cases. We aimed to improve IE diagnosis using an ultra-sensitive molecular technique on cardiac samples in microbiologically nondocumented (culture and conventional polymerase chain reaction [PCR]) IE (NDIE) cases.

Methods

Cardiac samples explanted in a tertiary hospital in Lyon, France, from patients with definite IE over a 5-year period were retrospectively analyzed. NDIE was defined as Duke definite-IE associated with negative explorations including cardiac samples culture, bacterial amplification, and serologies. Ultrasensitive molecular diagnosis was achieved using the Universal Microbe Detection kit (Molzym®). Fungal identification was confirmed using 26S-rDNA and internal transcribed spacer amplifications. Fungal infection was confirmed using Grocott-Gromori staining, auto-immunohistochemistry on cardiac samples, and mannan serologies.

Results

Among 88 included patients, microbial DNA was detected in all 16 NDIE cases. Bacterial taxa typical of IE etiologies were detected in 13/16 cases and Malassezia restricta in the 3 other cases. In these 3 cases, histological examination confirmed the presence of fungi pathognomonic of Malassezia that reacted with patient sera in an auto-immunohistochemistry assay and cross-reacted with Candida albicans in an indirect immunofluorescent assay.

Conclusions

M. restricta appears to be an underestimated causative agent of NDIE. Importantly, serological cross-reaction of M. restricta with C. albicans may lead to its misdiagnosis. This is of major concern since M. restricta is intrinsically resistant to echinocandins; the reference treatment for Candida-fungal IE.
Dynamic Effects of Co-Ethnic Networks on Immigrants’ Economic Success
Authors: Battisti Michele , Peri Giovanni , Romiti Agnese
Published: April 2021

In this paper we investigate how co-ethnic networks affect the economic success of immigrants. Using longitudinal data of immigrants in Germany and including a large set of fixed effects and pre-migration controls to address the possible endogeneity of initial location, we find that immigrants in districts with larger co-ethnic networks are more likely to be employed soon after arrival. This advantage fades after four years, as migrants located in places with smaller co-ethnic networks catch up due to greater human capital investments. These effects appear stronger for lower-skilled immigrants, as well as for refugees and ethnic Germans.
The Scar Effects of Unemployment on Electoral Participation: Withdrawal and Mobilization across European Societies
Authors: Azzollini Leo
Published: April 2021

Does unemployment increase or decrease electoral participation? A considerable body of work has examined this classic question, focusing on individual and contextual unemployment. However, this literature has scarcely examined the role of past experiences of unemployment, and not yet addressed their interaction with contextual unemployment. In this article, we extend the framework of unemployment scarring to study electoral behaviour. First, we posit that unemployment scars decrease electoral participation. Second, we formulate competing hypotheses on the macro–micro interactions between unemployment rates and scarring at the country, NUTS1 and 2 levels. We test these hypotheses relying on Rounds 4–8 (2008–2016) of the European Social Survey, for 26 countries. Results from logistic regressions with country and year fixed effects indicate that citizens with long unemployment scars are 9% less likely to vote than the non-scarred. We further find that higher unemployment rates at the sub-national levels slightly increase turnout, while there is no significant effect at the country level. For the sub-national levels, we find that lower unemployment rates exacerbate the individual scarring effect on turnout up to 13%. These findings remark that the framework of the scar effects of unemployment further illuminates the relationship between social stratification and political behaviour.
Short-coupled ventricular fibrillation represents a distinct phenotype among latent causes of unexplained cardiac arrest: a report from the CASPER registry
Authors: Steinberg Christian , Davies Brianna , Mellor Greg , Tadros Rafik , Laksman Zachary W , Roberts Jason D , Green Martin , Alqarawi Wael , Angaran Paul , Healey Jeffrey , Sanatani Shubhayan , Leather Richard , Seifer Colette , Fournier Anne , Duff Henry , Gardner Martin , McIntyre Ciorsti , Hamilton Robert , Simpson Christopher S , Krahn Andrew D
Published: April 2021

Aims 

The term idiopathic ventricular fibrillation (IVF) describes survivors of unexplained cardiac arrest (UCA) without a specific diagnosis after clinical and genetic testing. Previous reports have described a subset of IVF individuals with ventricular arrhythmia initiated by short-coupled trigger premature ventricular contractions (PVCs) for which the term short-coupled ventricular fibrillation (SCVF) has been proposed. The aim of this article is to establish the phenotype and frequency of SCVF in a large cohort of UCA survivors.

Methods and results 

We performed a multicentre study including consecutive UCA survivors from the CASPER registry. Short-coupled ventricular fibrillation was defined as otherwise unexplained ventricular fibrillation initiated by a trigger PVC with a coupling interval of <350 ms. Among 364 UCA survivors, 24/364 (6.6%) met diagnostic criteria for SCVF. The diagnosis of SCVF was obtained in 19/24 (79%) individuals by documented ventricular fibrillation during follow-up. Ventricular arrhythmia was initiated by a mean PVC coupling interval of 274 ± 32 ms. Electrical storm occurred in 21% of SCVF probands but not in any UCA proband (P < 0.001). The median time to recurrent ventricular arrhythmia in SCVF was 31 months. Recurrent ventricular fibrillation resulted in quinidine administration in 12/24 SCVF (50%) with excellent arrhythmia control.

Conclusion 

Short-coupled ventricular fibrillation is a distinct primary arrhythmia syndrome accounting for at least 6.6% of UCA. As documentation of ventricular fibrillation onset is necessary for the diagnosis, most cases are diagnosed at the time of recurrent arrhythmia, thus the true prevalence of SCVF remains still unknown. Quinidine is effective in SCVF and should be considered as first-line treatment for patients with recurrent episodes.
A Note on Algorithms for Genotype and Allele Elimination in Complex Pedigrees With Incomplete Genotype Data
Authors: Du F-X , Hoeschele I
Published: April 2021

Elimination of genotypes or alleles for each individual or meiosis, which are inconsistent with observed genotypes, is a component of various genetic analyses of complex pedigrees. Computational efficiency of the elimination algorithm is critical in some applications such as genotype sampling via descent graph Markov chains. We present an allele elimination algorithm and two genotype elimination algorithms for complex pedigrees with incomplete genotype data. We modify all three algorithms to incorporate inheritance restrictions imposed by a complete or incomplete descent graph such that every inconsistent complete descent graph is detected in any pedigree, and every inconsistent incomplete descent graph is detected in any pedigree without loops with the genotype elimination algorithms. Allele elimination requires less CPU time and memory, but does not always eliminate all inconsistent alleles, even in pedigrees without loops. The first genotype algorithm produces genotype lists for each individual, which are identical to those obtained from the Lange-Goradia algorithm, but exploits the half-sib structure of some populations and reduces CPU time. The second genotype elimination algorithm deletes more inconsistent genotypes in pedigrees with loops and detects more illegal, incomplete descent graphs in such pedigrees.
logjam Encodes a Predicted EMP24/GP25 Protein That Is Required for Drosophila Oviposition Behavior
Authors: Carney Ginger E , Taylor Barbara J
Published: April 2021

A newly characterized Drosophila melanogaster gene, logjam (loj), functions in female reproduction by modulating oviposition behavior. The locus encodes at least six overlapping transcripts with unique 5′ ends. P-element mutants that express very low levels of loj transcripts are unable to oviposit mature eggs. This phenotype can be rescued by the introduction of a transgene expressing the most abundant loj transcript. As for many genes that specify behavioral outputs, loj is present in the adult central nervous system (CNS). Interestingly, it is also observed in vitellogenic egg chambers, suggesting that there may be multiple functions for this gene in egg-laying behavior. loj encodes a predicted protein with homology to the EMP24/GP25 transmembrane components of cytoplasmic vesicles and likely functions in intracellular trafficking.
A DNA-Damage-Induced Cell Cycle Checkpoint in Arabidopsis
Authors: Preuss S B , Britt A B
Published: April 2021

Although it is well established that plant seeds treated with high doses of gamma radiation arrest development as seedlings, the cause of this arrest is unknown. The uvh1 mutant of Arabidopsis is defective in a homolog of the human repair endonuclease XPF, and uvh1 mutants are sensitive to both the toxic effects of UV and the cytostatic effects of gamma radiation. Here we find that gamma irradiation of uvh1 plants specifically triggers a G2-phase cell cycle arrest. Mutants, termed suppressor of gamma (sog), that suppress this radiation-induced arrest and proceed through the cell cycle unimpeded were recovered in the uvh1 background; the resulting irradiated plants are genetically unstable. The sog mutations fall into two complementation groups. They are second-site suppressors of the uvh1 mutant's sensitivity to gamma radiation but do not affect the susceptibility of the plant to UV radiation. In addition to rendering the plants resistant to the growth inhibitory effects of gamma radiation, the sog1 mutation affects the proper development of the pollen tetrad, suggesting that SOG1 might also play a role in the regulation of cell cycle progression during meiosis.
Power Evaluations for Family-Based Tests of Association With Incomplete Parental Genotypes
Authors: Yang Qiong , Xu Xin , Laird Nan
Published: April 2021

While a variety of methods have been developed to deal with incomplete parental genotype information in family-based association tests, sampling design issues with incomplete parental genotype data still have not received much attention. In this article, we present simulation studies with four genetic models and various sampling designs and evaluate power in family-based association studies. Efficiency depends heavily on disease prevalence. With rare diseases, sampling affecteds and their parents is preferred, and three sibs will be required to have close power if parents are unavailable. With more common diseases, sampling affecteds and two sibs will generally be more efficient than trios. When parents are unavailable, siblings need not be phenotyped if the disease is rare, but a loss of power will result with common diseases. Finally, for a class of complex traits where other genetic and environmental factors also cause phenotypic correlation among siblings, little loss of efficiency occurs to rare disease, but substantial loss of efficiency occurs to common disease.
A Coalescent Model of Recombination Hotspots
Authors: Wiuf Carsten , Posada David
Published: April 2021

Recent experimental findings suggest that the assumption of a homogeneous recombination rate along the human genome is too naive. These findings point to block-structured recombination rates; certain regions (called hotspots) are more prone than other regions to recombination. In this report a coalescent model incorporating hotspot or block-structured recombination is developed and investigated analytically as well as by simulation. Our main results can be summarized as follows: (1) The expected number of recombination events is much lower in a model with pure hotspot recombination than in a model with pure homogeneous recombination, (2) hotspots give rise to large variation in recombination rates along the genome as well as in the number of historical recombination events, and (3) the size of a (nonrecombining) block in the hotspot model is likely to be overestimated grossly when estimated from SNP data. The results are discussed with reference to the current debate about block-structured recombination and, in addition, the results are compared to genome-wide variation in recombination rates. A number of new analytical results about the model are derived.
Theory of the Effects of Population Structure and Sampling on Patterns of Linkage Disequilibrium Applied to Genomic Data From Humans
Authors: Wakeley John , Lessard Sabin
Published: April 2021

We develop predictions for the correlation of heterozygosity and for linkage disequilibrium between two loci using a simple model of population structure that includes migration among local populations, or demes. We compare the results for a sample of size two from the same deme (a single-deme sample) to those for a sample of size two from two different demes (a scattered sample). The correlation in heterozygosity for a scattered sample is surprisingly insensitive to both the migration rate and the number of demes. In contrast, the correlation in heterozygosity for a single-deme sample is sensitive to both, and the effect of an increase in the number of demes is qualitatively similar to that of a decrease in the migration rate: both increase the correlation in heterozygosity. These same conclusions hold for a commonly used measure of linkage disequilibrium (r2). We compare the predictions of the theory to genomic data from humans and show that subdivision might account for a substantial portion of the genetic associations observed within the human genome, even though migration rates among local populations of humans are relatively large. Because correlations due to subdivision rather than to physical linkage can be large even in a single-deme sample, then if long-term migration has been important in shaping patterns of human polymorphism, the common practice of disease mapping using linkage disequilibrium in “isolated” local populations may be subject to error.
Locus-Specific Genetic Differentiation at Rw Among Warfarin-Resistant Rat (Rattus norvegicus) Populations
Authors: Kohn Michael H , Pelz Hans-Joachim , Wayne Robert K
Published: April 2021

Populations may diverge at fitness-related genes as a result of adaptation to local conditions. The ability to detect this divergence by marker-based genomic scans depends on the relative magnitudes of selection, recombination, and migration. We survey rat (Rattus norvegicus) populations to assess the effect that local selection with anticoagulant rodenticides has had on microsatellite marker variation and differentiation at the warfarin resistance gene (Rw) relative to the effect on the genomic background. Initially, using a small sample of 16 rats, we demonstrate tight linkage of microsatellite D1Rat219 to Rw by association mapping of genotypes expressing an anticoagulant-rodenticide-insensitive vitamin K 2,3-epoxide reductase (VKOR). Then, using allele frequencies at D1Rat219, we show that predicted and observed resistance levels in 27 populations correspond, suggesting intense and recent selection for resistance. A contrast of FST values between D1Rat219 and the genomic background revealed that rodenticide selection has overwhelmed drift-mediated population structure only at Rw. A case-controlled design distinguished these locus-specific effects of selection at Rw from background levels of differentiation more effectively than a population-controlled approach. Our results support the notion that an analysis of locus-specific population genetic structure may assist the discovery and mapping of novel candidate loci that are the object of selection or may provide supporting evidence for previously identified loci.
Identification of a Topoisomerase I Mutant, scsA1, as an Extragenic Suppressor of a Mutation in scaANBS1, the Apparent Homolog of Human Nibrin in Aspergillus nidulans
Authors: Fagundes Marcia R Z Kress , Fernandes Larissa , Savoldi Marcela , Harris Steven D , Goldman Maria H S , Goldman Gustavo H
Published: April 2021

The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. Mutations in scaANBS1, which encodes the apparent homolog of human nibrin in Aspergillus nidulans, inhibit growth in the presence of the antitopoisomerase I drug camptothecin. This article describes the selection and characterization of extragenic suppressors of the scaA1 mutation, with the aim of identifying other proteins that interfere with the pathway or complex in which the ScaA would normally be involved. Fifteen extragenic suppressors of the scaA1 mutation were isolated. The topoisomerase I gene can complement one of these suppressors. Synergistic interaction between the scaANBS1 and scsATOP1 genes in the presence of DNA-damaging agents was observed. Overexpression of topoisomerase I in the scaA1 mutant causes increased sensitivity to DNA-damaging agents. The scsATOP1 and the scaANBS1 gene products could functionally interact in pathways that either monitor or repair DNA double-strand breaks.
Rapid, Selective Digestion of Mitochondrial DNA in Accordance With the matA Hierarchy of Multiallelic Mating Types in the Mitochondrial Inheritance of Physarum polycephalum
Authors: Moriyama Y , Kawano S
Published: April 2021

Although mitochondria are inherited uniparentally in nearly all eukaryotes, the mechanism for this is unclear. When zygotes of the isogamous protist Physarum polycephalum were stained with DAPI, the fluorescence of mtDNA in half of the mitochondria decreased simultaneously to give small spots and then disappeared completely ∼1.5 hr after nuclear fusion, while the other mitochondrial nucleoids and all of the mitochondrial sheaths remained unchanged. PCR analysis of single zygote cells confirmed that the loss was limited to mtDNA from one parent. The vacant mitochondrial sheaths were gradually eliminated by 60 hr after mating. Using six mating types, the transmission patterns of mtDNA were examined in all possible crosses. In 39 of 60 crosses, strict uniparental inheritance was confirmed in accordance with a hierarchy of relative sexuality. In the other crosses, however, mtDNA from both parents was transmitted to plasmodia. The ratio of parental mtDNA was estimated to be from 1:1 to 1:10-4. Nevertheless, the matA hierarchy was followed. In these crosses, the mtDNA was incompletely digested, and mtDNA replicated during subsequent plasmodial development. We conclude that the rapid, selective digestion of mtDNA promotes the uniparental inheritance of mitochondria; when this fails, biparental inheritance occurs.
Molecular Markers for Rapidly Identifying Candidate Genes in Chlamydomonas reinhardtii: ERY1 and ERY2 Encode Chloroplast Ribosomal Proteins
Authors: Bowers Amber K , Keller Jennifer A , Dutcher Susan K
Published: April 2021

To take advantage of available expressed sequence tags and genomic sequence, we have developed 64 PCR-based molecular markers in Chlamydomonas reinhardtii that map to the 17 linkage groups. These markers will allow the rapid association of a candidate gene sequence with previously identified mutations. As proof of principle, we have identified the genes encoded by the ERY1 and ERY2 loci. Mendelian mutations that confer resistance to erythromycin define three unlinked nuclear loci in C. reinhardtii. Candidate genes ribosomal protein L4 (RPL4) and L22 (RPL22) are tightly linked to the ERY1 locus and ERY2 locus, respectively. Genomic DNA for RPL4 from wild type and five mutant ery1 alleles was amplified and sequenced and three different point mutations were found. Two different glycine residues (G102 and G112) are replaced by aspartic acid and both are in the unstructured region of RPL4 that lines the peptide exit tunnel of the chloroplast ribosome. The other two alleles change a splice site acceptor site. Genomic DNA for RPL22 from wild type and three mutant ery2 alleles was amplified and sequenced and revealed three different point mutations. Two alleles have premature stop codons and one allele changes a splice site acceptor site.
DNA Variation in a Conifer, Cryptomeria japonica (Cupressaceae sensu lato)
Authors: Kado Tomoyuki , Yoshimaru Hiroshi , Tsumura Yoshihiko , Tachida Hidenori
Published: April 2021

We investigated the nucleotide variation of a conifer, Cryptomeria japonica, and the divergence between this species and its closest relative, Taxodium distichum, at seven nuclear loci (Acl5, Chi1, Ferr, GapC, HemA, Lcyb, and Pat). Samples of C. japonica were collected from three areas, Kantou-Toukai, Hokuriku, and Iwate. No apparent geographic differentiation was found among these samples. However, the frequency spectrum of the nucleotide polymorphism revealed excesses of intermediate-frequency variants, which suggests that the population was not panmictic and a constant size in the past. The average nucleotide diversity, π, for silent sites was 0.00383. However, values of π for silent sites vary among loci. Comparisons of polymorphism to divergence among loci (the HKA test) showed that the polymorphism at the Acl5 locus was significantly lower. We also observed a nearly significant excess of replacement polymorphisms at the Lcyb locus. These results suggested possibilities of natural selection acting at some of the loci. Intragenic recombination was detected only once at the Chi1 locus and was not detected at the other loci. The low level of population recombination rate, 4Nr, seemed to be due to both low level of recombination, r, and small population size, N.
Combining Gene Expression and Molecular Marker Information for Mapping Complex Trait Genes: A Simulation Study
Authors: Pérez-Enciso Miguel , Toro Miguel A , Tenenhaus Michel , Gianola Daniel
Published: April 2021

A method for mapping complex trait genes using cDNA microarray and molecular marker data jointly is presented and illustrated via simulation. We introduce a novel approach for simulating phenotypes and genotypes conditionally on real, publicly available, microarray data. The model assumes an underlying continuous latent variable (liability) related to some measured cDNA expression levels. Partial least-squares logistic regression is used to estimate the liability under several scenarios where the level of gene interaction, the gene effect, and the number of cDNA levels affecting liability are varied. The results suggest that: (1) the usefulness of microarray data for gene mapping increases when both the number of cDNA levels in the underlying liability and the QTL effect decrease and when genes are coexpressed; (2) the correlation between estimated and true liability is large, at least under our simulation settings; (3) it is unlikely that cDNA clones identified as significant with partial least squares (or with some other technique) are the true responsible cDNAs, especially as the number of clones in the liability increases; (4) the number of putatively significant cDNA levels increases critically if cDNAs are coexpressed in a cluster (however, the proportion of true causal cDNAs within the significant ones is similar to that in a no-coexpression scenario); and (5) data reduction is needed to smooth out the variability encountered in expression levels when these are analyzed individually.