Species-resolved, single-cell respiration rates reveal dominance of sulfate reduction in a deep continental subsurface ecosystem.

Rates of microbial processes are fundamental to understanding the significance of microbial impacts on environmental chemical cycling. However, it is often difficult to quantify rates or to link processes to specific taxa or individual cells, especially in environments where there are few cultured representatives with known physiology. Here, we describe the use of the redox-enzyme-sensitive molecular probe RedoxSensor™ Green to measure rates of anaerobic electron transfer physiology (i.e., sulfate reduction and methanogenesis) in individual cells and link those measurements to genomic sequencing of the same single cells. We used this method to investigate microbial activity in hot, anoxic, low-biomass (~103 cells mL-1) groundwater of the Death Valley Regional Flow System, California. Combining this method with electron donor amendment experiments and metatranscriptomics confirmed that the abundant spore formers including Candidatus Desulforudis audaxviator were actively reducing sulfate in this environment, most likely with acetate and hydrogen as electron donors. Using this approach, we measured environmental sulfate reduction rates at 0.14 to 26.9 fmol cell-1 h-1. Scaled to volume, this equates to a bulk environmental rate of ~103 pmol sulfate L-1 d-1, similar to potential rates determined with radiotracer methods. Despite methane in the system, there was no evidence for active microbial methanogenesis at the time of sampling. Overall, this method is a powerful tool for estimating species-resolved, single-cell rates of anaerobic metabolism in low-biomass environments while simultaneously linking genomes to phenomes at the single-cell level. We reveal active elemental cycling conducted by several species, with a large portion attributable to Ca. Desulforudis audaxviator.

Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian Cancer.

OBJECTIVES: The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era. METHODS: Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval. RESULTS: From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities. CONCLUSION: Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel.

Rates of genetic consultation in high-grade serous ovarian cancer patients in the era of PARP inhibitor therapy: A population-based study.

OBJECTIVE: The American Society of Clinical Oncology recommends all patients with high-grade serous ovarian carcinoma (HGSC) undergo germline genetic testing. Genetic consultation rates in Ontario, Canada, only reached 13.3% in 2011. In 2016, PARP inhibitor maintenance therapy became available in Ontario for BRCA-positive HGSC patients. Given expanding treatment options, we re-examined genetic consultation rates among HGSC patients. METHODS: This retrospective cohort study identified patients diagnosed with HGSC between 2012 and 2019 using population-based administrative data from Ontario. Genetics consultations were identified using Ontario Health Insurance Plan billing codes. Consultation rates over time were analyzed using Cochran-Armitage trend test and segmental regression analysis. Multivariable analysis identified factors associated with attending genetics consultation. RESULTS: This study included 4645 HGSC patients. The mean age was 64.2 years (±SD 12.3); 56.3% had stage 3-4 disease. Overall, approximately 35% attended genetics consultations. The genetic consultation rate per year increased significantly from 21.6% to 42.6% (P < 0.001). Shorter times between diagnosis and genetics consult were observed after PARP inhibitors became available (68.1 vs 34.1 weeks, P < 0.001). Patients treated at designated cancer centers (odds ratio [OR] 2.11, P < 0.001), diagnosed in later years (OR 1.33, P < 0.001), and from higher income groups (P < 0.05) were more likely to attend genetics consultation; older patients were less likely (OR 0.98, P < 0.001). After PARP inhibitors became available, consultation rates plateaued (P < 0.001). CONCLUSIONS: Between 2012 and 2019, genetic consultation rates improved significantly among HGSC patients; however, a large proportion of patients never attended consultation. Further exploration of barriers to care is warranted to improve consultation rates and ensure equitable access to care.

Real-world outcomes associated with use of front-line bevacizumab in ovarian cancer.

BACKGROUND: In the pivotal ICON7 study, addition of bevacizumab to front-line treatment of ovarian cancer (OC) significantly improved overall survival (OS) (p = 0.03) in a high-risk subgroup of patients with suboptimally debulked/unresectable stage III or IV disease, leading to approval in Ontario, Canada in March 2016. Here we describe utilization of bevacizumab for front-line, high-risk OC and determine outcomes in routine clinical practice. METHODS: Provincial administrative databases were utilized to identify all patients treated with front-line bevacizumab following its approval. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. A comparative effectiveness analysis was performed to determine mOS pre- (2006-2016) and post- (2016-2019) approval. RESULTS: From March 2016 to October 2019, 282 patients received bevacizumab. Mean age was 64 years old, and 58% had stage IV disease. Median survival was 29 months and was longer in stage III (37 months) compared to stage IV disease (28 months). In a comparative effectiveness analysis of patients with stage IV serous OC, post-approval uptake of bevacizumab was low (23%). Median OS was similar pre (26 months) and post (27 months) approval (HR 0.92, 0.75-1.12, p = 0.383). CONCLUSIONS: Survival in real-world patients treated with front-line bevacizumab is shorter than in pivotal clinical trials. Survival in stage IV serous patients has not significantly improved post public reimbursement of bevacizumab. This analysis was limited by poor uptake, however mOS was similar in patients who did and did not receive bevacizumab.

Understanding Characteristics, Treatment Patterns, and Clinical Outcomes for Individuals with Advanced or Recurrent Endometrial Cancer in Alberta, Canada: A Retrospective, Population-Based Cohort Study.

Endometrial cancer (EC) incidence has increased in recent decades. However, population-based outcomes data are limited. In this retrospective cohort study, we examined characteristics, treatment patterns, and clinical outcomes, including time to next treatment (TNNT) and overall survival (OS), among advanced/recurrent (A/R) EC patients between 2010 and 2018 in Alberta, Canada. Kaplan-Meier statistics evaluated TTNT and OS, stratified by patient (A/R) and treatment. A total of 1053 patients were included: 620 (58.9%) advanced and 433 (41.1%) recurrent. A total of 713 (67.7%) patients received first-line therapy: 466 (75.2%) advanced and 247 (57.0%) recurrent. Platinum-based chemotherapy (PBCT) was the most common first-line regimen (overall: 78.6%; advanced: 96.1%; recurrent: 45.3%). The median TTNT and OS from first-line therapy were 19.9 months (95% confidence interval [CI]: 17.5-23.5) and 35.9 months (95% CI: 31.5-53.5), respectively. Following first-line PBCT, the median OS from second-line chemotherapy (N = 187) was 10.4 months (95% CI: 8.9-13.3) and higher for those rechallenged with PBCT (N = 72; 38.5%) versus no rechallenge (N = 115; 61.5%) (13.3 months [95% CI: 11.2-20.9] vs. 6.4 months [95% CI: 4.6-10.4; p < 0.001]). The findings highlight poor outcomes in A/R EC, particularly following first-line therapy, and that additional tolerable therapeutic options are needed to improve patient outcomes.

Decoupling of respiration rates and abundance in marine prokaryoplankton.

The ocean-atmosphere exchange of CO2 largely depends on the balance between marine microbial photosynthesis and respiration. Despite vast taxonomic and metabolic diversity among marine planktonic bacteria and archaea (prokaryoplankton)1-3, their respiration usually is measured in bulk and treated as a 'black box' in global biogeochemical models4; this limits the mechanistic understanding of the global carbon cycle. Here, using a technology for integrated phenotype analyses and genomic sequencing of individual microbial cells, we show that cell-specific respiration rates differ by more than 1,000× among prokaryoplankton genera. The majority of respiration was found to be performed by minority members of prokaryoplankton (including the Roseobacter cluster), whereas cells of the most prevalent lineages (including Pelagibacter and SAR86) had extremely low respiration rates. The decoupling of respiration rates from abundance among lineages, elevated counts of proteorhodopsin transcripts in Pelagibacter and SAR86 cells and elevated respiration of SAR86 at night indicate that proteorhodopsin-based phototrophy3,5-7 probably constitutes an important source of energy to prokaryoplankton and may increase growth efficiency. These findings suggest that the dependence of prokaryoplankton on respiration and remineralization of phytoplankton-derived organic carbon into CO2 for its energy demands and growth may be lower than commonly assumed and variable among lineages.

Extramedullary plasmacytoma of the uterine cervix arising in an asymptomatic 46-year-old female.

An extramedullary plasmacytoma is a rare type of plasma cell tumour that can be found in soft tissues throughout the body. The most common location for an extramedullary plasmacytoma is in the head and neck region. Few case reports have previously documented patients with an extramedullary plasmacytoma within the female genital tract. We report a case of a healthy and asymptomatic 46-year-old female who presented to Colposcopy Clinic with a finding of low-grade squamous intraepithelial lesion seen on a routine Pap smear. She was found to have a cervical polyp that was excised. Pathology revealed diffuse sheets of atypical plasma cells with lambda light chain restriction. She was referred to Hematology for extensive work-up as the pathology finding was concerning for a plasma cell neoplasm. Staging investigations, including bone marrow biopsy, skeletal survey, whole body PET-CT scan, serum protein electrophoresis, and serum free light chain testing, were all negative. Surgical resection with a hysterectomy was recommended as the most appropriate course of management. The treatment approach is consistent with guidelines outlined in the literature, whereby extramedullary plasmacytomas, which arise outside of the head and neck region and have clear margins, should undergo surgical resection. Extramedullary plasmacytomas carry a risk of progressing to systemic disease, such as multiple myeloma, making it crucial that these patients be followed with routine surveillance to achieve the most optimal long term survival outcome.

Examining the Diagnostic Yield of Tumour Testing and Qualifying Germline Concordance for Hereditary Cancer Variants in Patients with High-Grade Serous Carcinoma.

Despite advances in treatment, prognosis for most patients with high-grade serous carcinoma (HGSC) remains poor. Genomic alterations in the homologous recombination (HR) pathway are used for cancer risk assessment and render tumours sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARPi), which can be associated with more favourable outcomes. In addition to patients with tumours containing BRCA1 or BRCA2 pathologic variants, there is emerging evidence that patients with tumours harbouring pathologic variants in other HR genes may also benefit from PARPi therapy. The objective of this study is to assess the feasibility of primary-tumour testing by examining the concordance of variant detection between germline and tumour-variant status using a custom hereditary cancer gene panel (HCP). From April 2019 to November 2020, HCP variant testing was performed on 146 HGSC formalin-fixed, paraffin-embedded tissue samples using next-generation sequencing. Of those, 78 patients also underwent HCP germline testing using blood samples. A pathogenic variant was detected in 41.1% (60/146) of tumours tested, with 68.3% (41/60) having either a BRCA1 or BRCA2 variant (n = 36), or BRCA1/2 plus a second variant (n = 5), and 31.2% (19/60) carrying a pathogenic variant in another HCP gene. The overall variant rate among the paired germline and tumour samples was 43.6% (34/78), with the remaining 56% (44/78) having no pathogenic variant detected in the germline or tumour. The overall BRCA1/2 variant rate for paired samples was 33.3% (26/78), with germline variants detected in 11.5% (9/78). A non-BRCA1/2 germline variant in another HCP gene was detected in 9.0% (7/78). All germline variants were detected in the tumour, demonstrating 100% concordance. These data provide evidence supporting the feasibility of primary-tumour testing for detecting germline and somatic variants in HCP genes in patients with HGSC, which can be used to guide clinical decision-making, and may provide opportunity for improving patient triage and clinical genetic referral practices.

Complication Rates after Endometrial Ablation in Ontario: A Cohort Analysis of 76 446 Patients.

STUDY OBJECTIVES: Endometrial ablation (EA) is an alternative to hysterectomy for the management of heavy menstrual bleeding; however, EA is not without risk. Our objective was to determine complication rates in women undergoing EA in the province of Ontario over a 15-year time period. The primary outcome was a composite of multiple complications within 30 to 180 days of surgery. The secondary outcomes included mortality, length of hospital stay, hospital readmission, and emergency department visit within 30 days of discharge. DESIGN: Retrospective cohort study using Cochran-Armitage test for trend. SETTING: Administrative data from the Canadian province of Ontario, assessing patients undergoing surgery in a publicly funded healthcare system. PATIENTS: Women in Ontario undergoing a primary EA over a 15-year time period. INTERVENTIONS: The intervention was a primary EA. MEASUREMENTS AND MAIN RESULTS: We assessed for genitourinary complication, fistula, gastrointestinal complication, pain, control of bleeding, blood transfusion, infectious complication, venous thromboembolism, fluid overload, thermal injury, and other injuries related to surgery. The secondary outcomes included 1-month and 6-month mortality, length of hospital stay, hospital readmission, and emergency department visit within 30 days of discharge. A total of 76 446 primary EAs were evaluated from 2002 to 2017, with the number of EAs per year increasing over the study period by 47%. Complications were seen in 4.8% of the cohort, with the complication rate being relatively stable over time. Although 6.2% of the cohort re-presented to the emergency department, <1% required readmission, and <0.05% died within 180 days. On multivariable analysis, the risk of complications increased with a preoperative diagnosis of other than bleeding (odds ratio [OR] 2.89; 95% confidence interval [CI], 2.61-3.21; p <.001), previous abdominal surgery (OR 1.42; 95% CI, 1.28-1.56; p <.001), and American Society of Anesthesiologists score 3+ (OR 1.37; 95% CI, 1.27-1.48; p <.001). CONCLUSION: Primary EA is associated with complications in <5% of the patients, with serious complications infrequent.

Real-World Treatment Patterns, Survival, and Costs for Ovarian Cancer in Canada: A Retrospective Cohort Study Using Provincial Administrative Data.

Background: In 2020, approximately 3100 Canadian women were diagnosed with ovarian cancer (OC), with 1950 women dying of this disease. Prognosis for OC remains poor, with 70% to 75% of cases diagnosed at an advanced stage and an overall 5-year survival of 46%. Current standard of care in Canada involves a combination of cytoreductive surgery and platinum-based chemotherapy. Objective: There are few studies reporting current OC costs. This study sought to determine patient characteristics and costs to the health system for OC in Ontario, Canada. Methods: Women diagnosed with OC in Ontario between 2010 and 2017 were identified. The cohort was linked to provincial administrative databases to capture treatment patterns, survival, and costs. Overall total and mean cost per patient (unadjusted) were reported in 2017 Canadian dollars, using a macro-based costing methodology called GETCOST. It is programmed to determine the costs of short-term and long-term episodes of health-care resources utilized. Results: Of the 2539 OC patients included in the study, the mean age at diagnosis was 60.4±11.35 years. The majority were diagnosed with stage III disease (n=1247). The only treatment required for 74% of stage I patients and 54% of stage II patients was first-line (1L) platinum chemotherapy; in advanced stages (III/IV) 24% and 20%, respectively, did not receive further treatment after 1L therapy. The median overall survival (mOS) for the whole cohort was 5.13 years. Survival was highest in earlier stage disease (mOS not reached in stage I/II), and dropped significantly in advanced stage patients (stage III: mOS=4.09 years; stage IV: mOS=3.47 years). Overall mean costs in patients stage I were CAD $58 099 compared to CAD $124 202 in stage IV. Discussion: The majority of OC patients continue to be diagnosed with advanced disease, which is associated with poor survival and increased treatment costs. Increased awareness and screening could facilitate diagnosis of earlier stage disease and reduce high downstream costs for advanced disease. Conclusion: Advanced OC is associated with poor survival and increased costs, mainly driven by hospitalizations or cancer clinic visits. The introduction of new targeted therapies such as olaparib could impact health system costs, by offsetting higher downstream costs while also improving survival.

A Case of Synchronous Malignant and Benign Granular Cell Tumor of the Vulva.

Granular cell tumors (GCT) are rare soft tissue neoplasms, which seldom occur in the vulva. They are more commonly benign, but malignant GCT do occur. We report a case of a 50-yr-old postmenopausal woman who presented with a vulvar lesion that was diagnosed as GCT on biopsy. Imaging and clinical examination revealed an enlarged, likely positive lymph node. Pathology of the subsequently resected total deep vulvectomy specimen showed 2 histologically distinct GCTs. The larger lesion met criteria for malignancy and histologically corresponded to metastatic deposits seen in the pelvic lymph nodes. The separate smaller lesion was histologically benign. This case illustrates a malignant GCT with a synchronous, likely benign GCT both occurring in the vulva. Our case demonstrates the application of histologic criteria in the diagnosis of malignant and benign GCT with discussion on the diagnosis and treatment of this rare tumor.

Persistent complete hydatidiform molar pregnancy following assisted reproductive technology in a gestational carrier: Case report.

A hydatidiform mole is a rare pathology associated with pregnancy, attributed to abnormal gametogenesis and fertilization. When assisted reproduction techniques (ART) are used, the incidence of molar pregnancy is significantly lower however not eliminated. We report a case of a patient serving as a gestational carrier who developed a complete molar pregnancy, with features indicating persistent trophoblastic disease. This 33-year-old G4T3P0A1L3 woman presented with bleeding at 8 weeks gestational age, after in vitro fertilization and frozen embryo transfer. Ultrasound findings and beta-HCG levels were consistent with molar pregnancy. Pathology specimen from D&C confirmed a complete hydatidiform mole. Despite surgical treatment, beta-HCG remained elevated and multiple pulmonary nodules and enlarged lymph nodes were noted on imaging. Methotrexate was considered but was deemed unnecessary because beta-HCG levels returned to normal over time and nodules resolved. Because molar pregnancy carries a risk of malignant transformation, albeit low, individuals undergoing ART should be counselled.

Genetic and epigenetic profiling of BRCA1/2 in ovarian tumors reveals additive diagnostic yield and evidence of a genomic BRCA1/2 DNA methylation signature.

Poly-ADP-ribose-polymerase inhibitor (PARPi) treatment is indicated for advanced-stage ovarian tumors with BRCA1/2 deficiency. The "BRCAness" status is thought to be attributed to a tumor phenotype associated with a specific epigenomic DNA methylation profile. Here, we examined the diagnostic impact of combined BRCA1/2 sequence, copy number, and promoter DNA methylation analysis, and evaluated whether genomic DNA methylation patterns can predict the BRCAness in ovarian tumors. DNA sequencing of 172 human tissue samples of advanced-stage ovarian adenocarcinoma identified 36 samples with a clinically significant tier 1/2 sequence variants (point mutations and in/dels) and 9 samples with a CNV causing a loss of function in BRCA1/2. DNA methylation analysis of the promoter of BRCA1/2 identified promoter hypermethylation of BRCA1 in two mutation-negative samples. Computational modeling of genome-wide methylation markers, measured using Infinium EPIC arrays, resulted in a total accuracy of 0.75, sensitivity: 0.83, specificity: 0.64, positive predictive value: 0.76, negative predictive value: 0.74, and area under the receiver's operating curve (AUC): 0.77, in classifying tumors harboring a BRCA1/2 defect from the rest. These findings indicate that the assessment of CNV and promoter DNA methylation in BRCA1/2 increases the cumulative diagnostic yield by 10%, compared with the 20% yield achieved by sequence variant analysis alone. Genomic DNA methylation data can partially predict BRCAness in ovarian tumors; however, further investigation in expanded BRCA1/2 cohorts is needed, and the effect of other double strand DNA repair gene defects in these tumors warrants further investigations.

Kindergarten to 12th Grade School-Based Nutrition Interventions: Putting Past Recommendations Into Practice.

School-based nutrition interventions are used to improve dietary habits of schoolchildren and reverse trends on obesity. This article reports on kindergarten through 12th grade nutrition interventions published between 2009 and 2018 compared with interventions published between 2000 and 2008 based on (1) behaviorally focused, (2) multicomponent, (3) healthful food/school environment (4) family involvement, (5) self-assessments, (6) quantitative evaluation, (7) community involvement, (8) ethnic/heterogeneous groups, (9) multimedia technology, and (10) sequential and sufficient duration. These 10 recommendations help guide educators, researchers, and nutritionists on more effective nutrition interventions. Future use of implementation science to determine potential drivers of adoption, nonadoption, and effectiveness of the recommendations is encouraged.

Discovery and Characterization of Thermoproteus Spherical Piliferous Virus 1: a Spherical Archaeal Virus Decorated with Unusual Filaments.

We describe the discovery of an archaeal virus, one that infects archaea, tentatively named Thermoproteus spherical piliferous virus 1 (TSPV1), which was purified from a Thermoproteales host isolated from a hot spring in Yellowstone National Park (USA). TSPV1 packages an 18.65-kb linear double-stranded DNA (dsDNA) genome with 31 open reading frames (ORFs), whose predicted gene products show little homology to proteins with known functions. A comparison of virus particle morphologies and gene content demonstrates that TSPV1 is a new member of the Globuloviridae family of archaeal viruses. However, unlike other Globuloviridae members, TSPV1 has numerous highly unusual filaments decorating its surface, which can extend hundreds of nanometers from the virion. To our knowledge, similar filaments have not been observed in any other archaeal virus. The filaments are remarkably stable, remaining intact across a broad range of temperature and pH values, and they are resistant to chemical denaturation and proteolysis. A major component of the filaments is a glycosylated 35-kDa TSPV1 protein (TSPV1 GP24). The filament protein lacks detectable homology to structurally or functionally characterized proteins. We propose, given the low host cell densities of hot spring environments, that the TSPV1 filaments serve to increase the probability of virus attachment and entry into host cells.IMPORTANCE High-temperature environments have proven to be an important source for the discovery of new archaeal viruses with unusual particle morphologies and gene content. Our isolation of Thermoproteus spherical piliferous virus 1 (TSPV1), with numerous filaments extending from the virion surface, expands our understanding of viral diversity and provides new insight into viral replication in high-temperature environments.

An Uncultivated Virus Infecting a Nanoarchaeal Parasite in the Hot Springs of Yellowstone National Park.

The Nanoarchaeota are small cells with reduced genomes that are found attached to and dependent on a second archaeal cell for their growth and replication. Initially found in marine hydrothermal environments and subsequently in terrestrial geothermal hot springs, the Nanoarchaeota species that have been described are obligate ectobionts, each with a different host species. However, no viruses had been described that infect the Nanoarchaeota. Here, we identify a virus infecting Nanoarchaeota by the use of a combination of viral metagenomic and bioinformatic approaches. This virus, tentatively named Nanoarchaeota Virus 1 (NAV1), consists of a 35.6-kb circular DNA genome coding for 52 proteins. We further demonstrate that this virus is broadly distributed among Yellowstone National Park hot springs. NAV1 is one of the first examples of a virus infecting a single-celled organism that is itself an ectobiont of another single-celled organism.IMPORTANCE Here, we present evidence of the first virus found to infect Nanoarchaeota, a symbiotic archaean found in acidic hot springs of Yellowstone National Park, USA. Using culture-independent techniques, we provide the genome sequence and identify the archaeal host species of a novel virus, NAV1. NAV1 is the first example of a virus infecting an archaeal species that is itself an obligate symbiont and dependent on a second host organism for growth and cellular replication. On the basis of annotation of the NAV1 genome, we propose that this virus is the founding member of a new viral family, further demonstrating the remarkable genetic diversity of archaeal viruses.

Resident Trainees Increase Surgical Time: A Comparison of Obstetric and Gynaecologic Procedures in Academic Versus Community Hospitals.

OBJECTIVE: The impact of resident involvement in the operating room for common procedures in obstetrics and gynaecology can shed light on the resource demands of teaching. The objective of this study was to quantify the increased surgical time associated with teaching obstetrics and gynaecology resident trainees across a range of procedures known to require surgical assistance. METHODS: This population-based retrospective cohort study compared surgical duration between academic (teaching) hospitals and community (non-teaching) hospitals. The cohort was made up of adult residents of Ontario between fiscal years 2002 and 2013 who were undergoing commonly performed obstetrics and gynaecologic procedures. The most commonly billed procedures requiring surgical assistance were included: cesarean section, anterior or posterior repair, anterior and posterior repair, salpingo-oophorectomy, myomectomy, ectopic pregnancy, total or subtotal hysterectomy, vaginal hysterectomy, and laparoscopic hysterectomy. Linked administrative databases held at the Institute of Clinical Evaluative Sciences (ICES) were used to define patient-, surgeon-, institution-, and procedure-related variables to limit confounding. Surgical duration, determined by anaesthetic billing records, was analyzed using a negative binomial regression. RESULTS: The total cohort included 337 389 surgical procedures. Of these procedures, 28% (94 203 procedures) were conducted in academic settings. The mean surgical duration of the procedures of interest (excluding vaginal hysterectomy) was significantly longer in academic hospitals compared with community hospitals. With many controls for case variability, this time differential reflects the burden of teaching resident trainees and other learners in the academic environment. The operating time increased between 6% and 20% for cases completed in academic centres versus in the community. As an example, the mean surgical duration of cesarean sections was 20.6 minutes (19%) longer in academic centres. Furthermore, the data highlighted a trend of increased teaching time for laparoscopic procedures compared with open procedures. The time ratio was the greatest for salpingo-oophortectomy and surgical management of ectopic pregnancies. The additional cost of carrying out these nine procedures in academic centres during the study period was $16.3 million. CONCLUSION: The cost of teaching resident trainees is increased operative time. This increased surgical cost in a publicly funded system must be considered as funding models evolve.

The Molecular Mechanism of Cellular Attachment for an Archaeal Virus.

Sulfolobus turreted icosahedral virus (STIV) is a model archaeal virus and member of the PRD1-adenovirus lineage. Although STIV employs pyramidal lysis structures to exit the host, knowledge of the viral entry process is lacking. We therefore initiated studies on STIV attachment and entry. Negative stain and cryoelectron micrographs showed virion attachment to pili-like structures emanating from the Sulfolobus host. Tomographic reconstruction and sub-tomogram averaging revealed pili recognition by the STIV C381 turret protein. Specifically, the triple jelly roll structure of C381 determined by X-ray crystallography shows that pilus recognition is mediated by conserved surface residues in the second and third domains. In addition, the STIV petal protein (C557), when present, occludes the pili binding site, suggesting that it functions as a maturation protein. Combined, these results demonstrate a role for the namesake STIV turrets in initial cellular attachment and provide the first molecular model for viral attachment in the archaeal domain of life.

Survey of high-resolution archaeal virus structures.

Archaeal viruses exhibit diverse morphologies whose structures are just beginning to be explored at high-resolution. In this review, we update recent findings on archaeal structural proteins and virion architectures and place them in the biological context in which these viruses replicate. We conclude that many of the unusual structural features and dynamics of archaeal viruses aid their replication and survival in the chemically harsh environments, in which they replicate. Furthermore, we should expect to find more novel features from examining the high-resolution structures of additional archaeal viruses.