Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity. PATIENTS AND METHODS: Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction. RESULTS: The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS (P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase. CONCLUSION: Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

Molecular responses of sponge larvae exposed to partially weathered condensate oil.

Anthropogenic inputs of petroleum hydrocarbons into the marine environment can have long lasting impacts on benthic communities. Sponges form an abundant and diverse component of benthic habitats, contributing a variety of important functional roles; however, their responses to petroleum hydrocarbons are largely unknown. This study combined a traditional ecotoxicological experimental design and endpoint with global gene expression profiling and microbial indicator species analysis to examine the effects of a water accommodated fraction (WAF) of condensate oil on a common Indo-Pacific sponge, Phyllospongia foliascens. A no significant effect concentration (N(S)EC) of 2.1 % WAF was obtained for larval settlement, while gene-specific (N(S)EC) thresholds ranged from 3.4 % to 8.8 % WAF. Significant shifts in global gene expression were identified at WAF treatments ≥20 %, with larvae exposed to 100 % WAF most responsive. Results from this study provide an example on the incorporation of non-conventional molecular and microbiological responses into ecotoxicological studies on petroleum hydrocarbons.

Effects of aromatic hydrocarbons and evaluation of oil toxicity modelling for larvae of a tropical coral.

Application of oil toxicity modelling for assessing the risk of spills to coral reefs remains uncertain due to a lack of data for key tropical species and environmental conditions. In this study, larvae of the coral Acropora millepora were exposed to six aromatic hydrocarbons individually to generate critical target lipid body burdens (CTLBBs). Larval metamorphosis was inhibited by all six aromatic hydrocarbons, while larval survival was only affected at concentrations >2000 µg L-1. The derived metamorphosis CTLBB of 9.7 µmol g-1 octanol indicates larvae are more sensitive than adult corals, and places A. millepora larvae among the most sensitive organisms in the target lipid model (TLM) databases. Larvae were also more sensitive to anthracene and pyrene when co-exposed to ecologically relevant levels of ultraviolet radiation. The results suggest that the application of the phototoxic TLM would be protective of A. millepora larvae, provided adequate chemical and light data are available.

Sexual harassment, sexual assault and rape by colleagues in the surgical workforce, and how women and men are living different realities: observational study using NHS population-derived weights.

BACKGROUND: This observational study, paired with National Health Service (NHS) workforce population data, examined gender differences in surgical workforce members' experiences with sexual misconduct (sexual harassment, sexual assault, rape) among colleagues in the past 5 years, and their views of the adequacy of accountable organizations in dealing with this issue. METHODS: This was a survey of UK surgical workforce members, recruited via surgical organizations. RESULTS: Some 1704 individuals participated, with 1434 (51.5 per cent women) eligible for primary unweighted analyses. Weighted analyses, grounded in NHS England surgical workforce population data, used 756 NHS England participants. Weighted and unweighted analyses showed that, compared with men, women were significantly more likely to report witnessing, and be a target of, sexual misconduct. Among women, 63.3 per cent reported being the target of sexual harassment versus 23.7 per cent of men (89.5 per cent witnessing versus 81.0 per cent of men). Additionally, 29.9 per cent of women had been sexually assaulted versus 6.9 per cent of men (35.9 per cent witnessing versus 17.1 per cent of men), with 10.9 per cent of women experiencing forced physical contact for career opportunities (a form of sexual assault) versus 0.7 per cent of men. Being raped by a colleague was reported by 0.8 per cent of women versus 0.1 per cent of men (1.9 per cent witnessing versus 0.6 per cent of men). Evaluations of organizations' adequacy in handling sexual misconduct were significantly lower among women than men, ranging from a low of 15.1 per cent for the General Medical Council to a high of 31.1 per cent for the Royal Colleges (men's evaluations: 48.6 and 60.2 per cent respectively). CONCLUSION: Sexual misconduct in the past 5 years has been experienced widely, with women affected disproportionately. Accountable organizations are not regarded as dealing adequately with this issue.

This research examined sexual misconduct occurring in surgery in the UK, so that more informed and targeted actions can be taken to make healthcare safer for staff and patients. A survey assessed individuals' experiences with being sexually harassed, sexually assaulted, and raped by work colleagues. Individuals were also asked whether they had seen this happen to others at work. Compared with men, women were much more likely to have seen sexual misconduct happening to others, and to have it happen to them. For example, most women (63.3 per cent) experienced being sexually harassed by colleagues, as did some men (23.7 per cent). Women also experienced being sexual assaulted by colleagues far more often than men (29.9 per cent of women, 6.9 per cent of men). These findings show that women and men in the surgical workforce are living different realities. For women, being around colleagues is more often going to mean witnessing, and being a target of, sexual misconduct. Individuals were also asked whether they thought healthcare-related organizations were handling issues of sexual misconduct adequately; most did not think they were. The General Medical Council (GMC) received the lowest evaluations. Only 15.1 per cent of women regarded the GMC as adequate in their handling of sexual misconduct. Men's evaluations were higher, although the GMC was still regarded as adequate by less than half of men (48.6 per cent). Evaluations of National Health Service Trusts were rated similarly low. Only 15.8 per cent of women evaluated them as adequate (44.9 per cent of men). The results of this study have implications for all stakeholders, including patients. Sexual misconduct was commonly experienced by respondents, representing a serious issue for the profession. There is a widespread lack of faith in the UK organizations responsible for dealing with this issue. Those organizations have a duty to protect the workforce, and to protect patients.

The Successful Implementation of a Laparoscopic Simulation Training Program in the Dominican Republic.

INTRODUCTION: Mount Sinai Hospital in New York introduced a laparoscopic surgery simulation center to a public hospital in Santiago, Dominican Republic to determine the feasibility of training programs in low-and-middle income countries (LMICs). METHODS: In August 2018, recruitment and preliminary data were collected at the Hospital Jose Maria Cabral y Báez in Santiago, Dominican Republic. The simulation room consists of three simulation stations. Residents were required to practice 1 h/wk guided by a general surgery postgraduate year 3 (PGY3) Mount Sinai resident. Number of hours practiced was self-reported and follow-up data was collected in June 2019. The study endpoints include times on three simulated laparoscopic tasks including peg-transfer, precision cutting, and intracorporeal knot tying. Wilcoxon-signed rank tests were used for statistical analysis. RESULTS: The partnership between hospitals allowed for successful integration into the Dominican general surgery training. Over 10 mo, residents averaged 25 h of practice (range: 8-35 h; SD 9.95 h). In total, 85% of the residents participated in the study (5 postgraduate year 1 [PGY1], 2 postgraduate year 2 [PGY2], and 4 postgraduate year 3 [PGY3]). Resident median simulation times significantly improved for precision cutting (3:49 min versus 2:09 min, P = 0.002) and intracorporeal knot tying (5:20 min versus 2:47 min, P = 0.037). There was neither significant difference in peg-transfer times nor performance between resident years (P = 0.12). CONCLUSIONS: This study demonstrates the successful integration of a laparoscopic simulation program into an LMIC surgical resident training program. With commitment from local institutions and external resources, establishing laparoscopic simulation centers are feasible and expandable, thereby allowing general surgery residents in other LMICs, the opportunity to improve their laparoscopic skills.

Assessment of Technical Skills in Axillary Lymph Node Dissection.

OBJECTIVE: A simulator to enable safe practice and assessment of ALND has been designed, and face, content and construct validity has been investigated. SUMMARY AND BACKGROUND DATA: The reduction in the number of ALNDs conducted has led to decreased resident exposure and confidence. METHODS: A cross-sectional multicenter observational study was carried out between July 2017 and August 2018. Following model development, 30 surgeons of varying experience (n = "experts," n = 11 "senior residents," and n = 10 "junior residents") were asked to perform a simulated ALND. Face and content validity questionnaires were administered immediately after ALND. All ALND procedures were retrospectively assessed by 2 attending breast surgeons, blinded to operator identity, using a video-based assessment tool, and an end product assessment tool. RESULTS: Statistically significant differences between groups were observed across all operative subphases on the axillary clearance assessment tool (P < 0.001). Significant differences between groups were observed for overall procedure quality (P < 0.05) and total number of lymph nodes harvested (P < 0.001). However, operator grade could not be distinguished across other end product variables such as axillary vein damage (P = 0.864) and long thoracic nerve injury (P = 0.094). Overall, participants indicated that the simulator has good anatomical (median score >7) and procedural realism (median score >7). CONCLUSIONS: Video-based analysis demonstrates construct validity for ALND assessment. Given reduced ALND exposure, this simulation is a useful adjunct for both technical skills training and formative Deanery or Faculty administered assessments.

Derivation of toxicity thresholds for gas condensate oils protective of tropical species using experimental and modelling approaches.

Toxicity thresholds for dissolved oil applied in tropical ocean risk assessments are largely based on the sensitivities of temperate and/or freshwater species. To explore the suitability of these thresholds for tropical habitats we experimentally determined toxicity thresholds for eight tropical species for a partially weathered gas condensate, applied the target lipid model (TLM) to predict toxicity of fresh and weathered condensates and compared sensitivities of the tropical species with model predictions. The experimental condensate-specific hazard concentration (HC5) was 167 µg L-1 total aromatic hydrocarbons (TAH), with the TLM-modelled HC5 (78 µg L-1 TAH) being more conservative, supporting TLM-modelled thresholds for tropical application. Putative species-specific critical target lipid body burdens (CTLBBs) indicated that several of the species tested were among the more sensitive species in the TLM database ranging from 5.1 (coral larvae) to 97 (sponge larvae) µmol g-1 octanol and can be applied in modelling risk for tropical marine ecosystems.

SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status - Los Angeles County, California, May 1-July 25, 2021.

COVID-19 vaccines fully approved or currently authorized for use through Emergency Use Authorization from the Food and Drug Administration are critical tools for controlling the COVID-19 pandemic; however, even with highly effective vaccines, a proportion of fully vaccinated persons will become infected with SARS-CoV-2, the virus that causes COVID-19 (1). To characterize postvaccination infections, the Los Angeles County Department of Public Health (LACDPH) used COVID-19 surveillance and California Immunization Registry 2 (CAIR2) data to describe age-adjusted infection and hospitalization rates during May 1-July 25, 2021, by vaccination status. Whole genome sequencing (WGS)-based SARS-CoV-2 lineages and cycle threshold (Ct) values from qualitative reverse transcription-polymerase chain reaction (RT-PCR) for two SARS-CoV-2 gene targets, including the nucleocapsid (N) protein gene region and the open reading frame 1 ab (ORF1ab) polyprotein gene region,* were reported for a convenience sample of specimens. Among 43,127 reported SARS-CoV-2 infections in Los Angeles County residents aged ≥16 years, 10,895 (25.3%) were in fully vaccinated persons, 1,431 (3.3%) were in partially vaccinated persons, and 30,801 (71.4%) were in unvaccinated persons. Much lower percentages of fully vaccinated persons infected with SARS-CoV-2 were hospitalized (3.2%), were admitted to an intensive care unit (0.5%), and required mechanical ventilation (0.2%) compared with partially vaccinated persons (6.2%, 1.0%, and 0.3%, respectively) and unvaccinated persons (7.6%, 1.5%, and 0.5%, respectively) (p<0.001 for all comparisons). On July 25, the SARS-CoV-2 infection rate among unvaccinated persons was 4.9 times and the hospitalization rate was 29.2 times the rates among fully vaccinated persons. During May 1-July 25, the percentages of B.1.617.2 (Delta) variant infections estimated from 6,752 samples with lineage data increased among fully vaccinated persons (from 8.6% to 91.2%), partially vaccinated persons (from 0% to 88.1%), and unvaccinated persons (from 8.2% to 87.1%). In May, there were differences in median Ct values by vaccination status; however, by July, no differences were detected among specimens from fully vaccinated, partially vaccinated, and unvaccinated persons by gene targets. These infection and hospitalization rate data indicate that authorized vaccines were protective against SARS-CoV-2 infection and severe COVID-19 during a period when transmission of the Delta variant was increasing. Efforts to increase COVID-19 vaccination, in coordination with other prevention strategies, are critical to preventing COVID-19-related hospitalizations and deaths.

Metastatic Malignant Melanoma With Occult Primary Presenting as Breast Mass: A Case Report and Literature Review.

Skin malignant melanoma (MM) is a malignant neoplasm that arises from the melanocytes in the basal layer of the epidermis. It is considered an aggressive neoplasm and is responsible for 75% of skin cancer deaths. Here we present a case of a young female patient who presented with a left breast mass and investigations revealed multiple disease foci from an occult MM.

Utility of Abnormal Head Computed Tomography in Predicting Outcome in Out-of-Hospital Cardiac Arrest Victims.

Head computed tomography (HCT) is often performed postcardiac arrest to assess for hypoxic-ischemic brain injury. Our primary objective was to assess whether cerebral edema (CE) on early HCT is associated with poor survival and neurologic outcome after out-of-hospital cardiac arrest (OHCA).We included subjects from a prospectively collected database of OHCA adults who received targeted temperature management at two hospitals from July 2009 to July 2018. We included cases if an emergency department (ED) HCT was performed. Patient demographics and cardiac arrest variables were collected. HCT results were abstracted from radiology reports. HCT findings were categorized as no acute disease, evidence of CE, or excluded (bleed, tumor, and stroke). Outcomes were survival to discharge or dichotomized discharge cerebral performance category (CPC) of 1-2 (good neurologic outcome) versus 3-5 (poor neurologic outcome). Univariate and multivariate analyses were performed. There were 425 OHCA, of which 315 had ED HCT with 277 cases included. Patients were predominately male (65.0%), average age of 60.9 years and average body mass index of 30.5. Of all cases, 44 (15.9%) showed CE on computed tomography. Univariate analysis demonstrated that CE was associated with 9.2-fold greater odds of poor outcome (odds ratio [OR]: 9.23; 95% confidence interval [CI] 1.73-49.2) and 9.1-fold greater odds of death (OR: 9.09, 95% CI 2.4-33.9). In adjusted analysis, CE was associated with a poor CPC outcome (adjusted odds ratios [AOR]: 14.9, 95% CI 2.49-88.4), and death (AOR: 13.7, 95% CI 3.26-57.4). Adjusted survival analysis demonstrated that patients with CE on HCT had 3.6-fold greater hazard of death than those without CE (hazard ratios 3.56, 95% CI 2.34-5.41). The results identify that CE on HCTs early in the postarrest period in OHCA patients is strongly associated with poor rates of survival and neurologic outcome. Prospective work is needed to further define the role of early HCT in postarrest neuroprognostication.

Methane flux from flowback operations at a shale gas site.

We report measurements of methane (CH4) mixing ratios and emission fluxes derived from sampling at a monitoring station at an exploratory shale gas extraction facility in Lancashire, England. Elevated ambient CH4 mixing ratios were recorded in January 2019 during a period of cold-venting associated with a nitrogen lift process at the facility. These processes are used to clear the well to stimulate flow of natural gas from the target shale. Estimates of CH4 flux during the emission event were made using three independent modeling approaches: Gaussian plume dispersion (following both a simple Gaussian plume inversion and the US EPA OTM 33-A method), and a Lagrangian stochastic transport model (WindTrax). The three methods yielded an estimated peak CH4 flux during January 2019 of approximately 70 g s-1. The total mass of CH4 emitted during the six-day venting period was calculated to be 2.9, 4.2 ± 1.4(1σ) and 7.1 ± 2.1(1σ) tonnes CH4 using the simple Gaussian plume model, WindTrax, and OTM-33A methods, respectively. Whilst the flux approaches all agreed within 1σ uncertainty, an estimate of 4.2 (± 1.4) tonnes CH4 represents the most confident assessment due to the explicit modeling of advection and meteorological stability permitted using the WindTrax model. This mass is consistent with fluxes calculated by the Environment Agency (in the range 2.7 to 6.8 tonnes CH4), using emission data provided by the shale site operator to the regulator. This study provides the first CH4 emission estimate for a nitrogen lift process and the first-reported flux monitoring of a UK shale gas site, and contributes to the evaluation of the environmental impacts of shale gas operations worldwide. This study also provides forward guidance on future monitoring applications and flux calculation in transient emission events. Implications: This manuscript discusses atmospheric measurements near to the UK's first hydraulic fracturing facility, which has very high UK public, media, and policy interest. The focus of this manuscript is on a single week of data in which a large venting event at the shale gas site saw emissions of ~4 tonnes of methane to atmosphere, in breach of environmental permits. These results are likely to beresults are likely to be reported by the media and may influence future policy decisions concerning the UK hydraulic fracturing industry.

The Challenge of COVID-19: The Biological Characteristics and Outcomes in a Series of 130 Breast Cancer Patients Operated on During the Pandemic.

Background: The worldwide outbreak of the 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China close to the end of 2019. We analyse the clinical characteristics and management outcomes of a small group of patients who have been treated in the early stage of the COVID-19 disease, and discuss the impact of the pandemic on the service delivered to breast cancer patients. Material Methods: We analysed a cohort of 130 breast cancer patients who underwent elective surgical procedures during the early period of COVID-19. The patients were operated on in the period from March 16th, 2020 to May 18th, 2020. Results: All the patients were female, with an age range of 33-88 years, with a median age of 57.6 years. Most of the cases were admitted as a day case surgery after passing through a preoperative screening pathway, which was developed gradually. Patients were contacted by phone after their surgery to ensure that they have had no symptoms and were reviewed in person two weeks after the procedure with histology results. Only one patient developed COVID-19 symptoms after surgery and recovered. Conclusions: Early and careful implementation of modified practice policies during emerging situation of viral pandemics will reduce the risk of perioperative complications, reduce the risk of patient to staff to patient transmission and minimize the negative impact of COVID-19 on breast cancer management.

Out-of-hours primary care end of life prescribing: a data linkage study.

OBJECTIVES: Out-of-hours (OOH) primary care services are contacted in the last 4 weeks of life by nearly 30% of all patients who die, but OOH palliative prescribing remains poorly understood. Our understanding of prescribing demand has previously been limited by difficulties identifying palliative patients seen OOH. This study examines the volume and type of prescriptions issued by OOH services at the end of life. METHODS: A retrospective cohort study was performed by linking a database of Oxfordshire OOH service contacts over a year with national mortality data, identifying patients who died within 30 days of OOH contact. Demographic, service and prescribing data were analysed. RESULTS: A prescription is issued at 14.2% of contacts in the 30 days prior to death, compared with 29.9% of other contacts. The most common prescriptions were antibiotics (22.2%) and strong opioids (19%). 41.8% of prescriptions are for subcutaneously administered medication. Patients who were prescribed a syringe driver medication made twice as many OOH contacts in the 30 days prior to death compared with those who were not. CONCLUSION: Absolute and relative prescribing rates are low in the 30 days prior to death. Further research is required to understand what occurs at these non-prescribing end of life contacts to inform how OOH provision can best meet the needs of dying patients. Overall, relatively few patients are prescribed strong opioids or syringe drivers. When a syringe driver medication is prescribed this may help identify patients likely to be in need of further support from the service.

Noncanonical Wnt as a prognostic marker in prostate cancer: "you can't always get what you Wnt".

Introduction: Wnt signaling is important for normal development, cell proliferation, and cell differentiation. However, aberrations in the pathway can lead to tumorigenesis and cancer progression. Recent genome-wide studies have demonstrated the frequent occurrence of Wnt pathway alterations in prostate cancer. Although alterations in the canonical Wnt pathway in prostate cancer may have an impact on prognosis, recent studies suggest that the noncanonical Wnt pathway also plays an important role in disease progression and treatment resistance.Areas covered: We review the literature with regard to the potential prognostic significance of noncanonical Wnt signaling in prostate cancer. After a brief overview of the canonical and noncanonical Wnt pathways, we discuss the preclinical and clinical evidence for activation of Wnt signaling in prostate cancer. We focus on clinical evidence for noncanonical Wnt pathway components to serve as potential prognostic biomarkers.Expert opinion: Although many therapeutic options are available for men with prostate cancer, there remains an unmet need for prognostic and predictive biomarkers to precisely guide clinical management. Early evidence suggests that components of the noncanonical Wnt pathway may serve as prognostic biomarkers. However, prospective validation studies are necessary before these biomarkers can be routinely applied in the clinic.

Environmental baseline monitoring for shale gas development in the UK: Identification and geochemical characterisation of local source emissions of methane to atmosphere.

Baseline mobile surveys of methane sources using vehicle-mounted instruments have been performed in the Fylde and Ryedale regions of Northern England over the 2016-19 period around proposed unconventional (shale) gas extraction sites. The aim was to identify and characterise methane sources ahead of hydraulically fractured shale gas extraction in the area around drilling sites. This allows a potential additional source of emissions to atmosphere to be readily distinguished from adjacent sources, should gas production take place. The surveys have used ethane:methane (C2:C1) ratios to separate combustion, thermogenic gas and biogenic sources. Sample collection of source plumes followed by high precision δ13C analysis of methane, to separate and isotopically characterise sources, adds additional biogenic source distinction between active and closed landfills, and ruminant eructations from manure. The surveys show that both drill sites and adjacent fixed monitoring sites have cow barns and gas network pipeline leaks as sources of methane within a 1 km range. These two sources are readily separated by isotopes (δ13C of -67 to -58‰ for barns, compared to -43 to -39‰ for gas leaks), and ethane:methane ratios (<0.001 for barns, compared to >0.05 for gas leaks). Under a well-mixed daytime atmospheric boundary layer these sources are generally detectable as above baseline elevations up to 100 m downwind for gas leaks and up to 500 m downwind for populated cow barns. It is considered that careful analysis of these proxies for unconventional production gas, if and when available, will allow any fugitive emissions from operations to be distinguished from surrounding sources.

A baseline of atmospheric greenhouse gases for prospective UK shale gas sites.

We report a 24-month statistical baseline climatology for continuously-measured atmospheric carbon dioxide (CO2) and methane (CH4) mixing ratios linked to surface meteorology as part of a wider environmental baselining project tasked with understanding pre-existing local environmental conditions prior to shale gas exploration in the United Kingdom. The baseline was designed to statistically characterise high-precision measurements of atmospheric composition gathered over two full years (between February 1st 2016 and January 31st 2018) at fixed ground-based measurement stations on, or near to, two UK sites being developed for shale gas exploration involving hydraulic fracturing. The sites, near Blackpool (Lancashire) and Kirby Misperton (North Yorkshire), were the first sites approved in the UK for shale gas exploration since a moratorium was lifted in England. The sites are operated by Cuadrilla Resources Ltd. and Third Energy Ltd., respectively. A statistical climatology of greenhouse gas mixing ratios linked to prevailing local surface meteorology is presented. This study diagnoses and interprets diurnal, day-of-week, and seasonal trends in measured mixing ratios and the contributory role of local, regional and long-range emission sources. The baseline provides a set of contextual statistical quantities against which the incremental impacts of new activities (in this case, future shale gas exploration) can be quantitatively assessed. The dataset may also serve to inform the design of future case studies, as well as direct baseline monitoring design at other potential shale gas and industrial sites. In addition, it provides a quantitative reference for future analyses of the impact, and efficacy, of specific policy interventions or mitigating practices. For example, statistically significant excursions in measured concentrations from this baseline (e.g. >99th percentile) observed during phases of operational extraction may be used to trigger further examination in order to diagnose the source(s) of emission and links to on-site activities at the time, which may be of importance to regulators, site operators and public health stakeholders. A guideline algorithm for identifying these statistically significant excursions, or "baseline deviation events", from the expected baseline conditions is presented and tested. Gaussian plume modelling is used to further these analyses, by simulating approximate upper-limits of CH4 fluxes which could be expected to give observable enhancements at the monitoring stations under defined meteorological conditions.

Three-dimensional architecture of epithelial primary cilia.

We report a complete 3D structural model of typical epithelial primary cilia based on structural maps of full-length primary cilia obtained by serial section electron tomography. Our data demonstrate the architecture of primary cilia differs extensively from the commonly acknowledged 9+0 paradigm. The axoneme structure is relatively stable but gradually evolves from base to tip with a decreasing number of microtubule complexes (MtCs) and a reducing diameter. The axonemal MtCs are cross-linked by previously unrecognized fibrous protein networks. Such an architecture explains why primary cilia can elastically withstand liquid flow for mechanosensing. The nine axonemal MtCs in a cilium are found to differ significantly in length indicating intraflagellar transport processes in primary cilia may be more complicated than that reported for motile cilia. The 3D maps of microtubule doublet-singlet transitions generally display longitudinal gaps at the inner junction between the A- and B-tubules, which indicates the inner junction protein is a major player in doublet-singlet transitions. In addition, vesicles releasing from kidney primary cilia were observed in the structural maps, supporting that ciliary vesicles budding may serve as ectosomes for cell-cell communication.