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Next-generation sequencing (NGS) technologies are high-throughput methods for DNA sequencing and have become a widely adopted tool in cancer research. The sheer amount and variety of data generated by NGS assays require sophisticated computational methods and bioinformatics expertise. In this review, we provide background details of NGS technology and basic bioinformatics concepts for the clinician investigator interested in cancer research applications, with a focus on DNA-based approaches. We introduce the general principles of presequencing library preparation, postsequencing alignment, and variant calling. We also highlight the common variant annotations and NGS applications for other molecular data types. Finally, we briefly discuss the revealed utility of NGS methods in NSCLC research and study design considerations for research studies that aim to leverage NGS technologies for clinical care.

BACKGROUND Laparoscopic subtotal cholecystectomy is a recognised safe, alternative strategy when a critical view of safety cannot be obtained. This study audits the change in practice at a District General Hospital following the adoption of subtotal cholecystectomy in 2013. METHODS Retrospective case series included consecutive cholecystectomies over a ten-year period in a single institution. Cases were divided into subgroups based on operation date. Primary outcome was the proportion of patients undergoing laparoscopic total cholecystectomy, laparoscopic subtotal and laparoscopic converted to open cholecystectomy. Secondary outcomes included incidence of bile leak, complication rate, return to theatre, and length of stay. RESULTS There were 4217 cases: 1381 in Group A (pre-adoption of subtotal cholecystectomy 2009-2012), and 2836 in Group B (post-adoption of subtotal cholecystectomy 2013-2019). The rate of laparoscopic total cholecystectomy was higher in Group A than Group B (95.4% vs. 92.8%, p

We present a technique to automatically classify the wave type of seismic phases that are recorded on a single six-component recording station (measuring both three components of translational and rotational ground motion) at the earth's surface. We make use of the fact that each wave type leaves a unique 'fingerprint' in the six-component motion of the sensor. This fingerprint can be extracted by performing an eigenanalysis of the data covariance matrix, similar to conventional three-component polarization analysis. To assign a wave type to the fingerprint extracted from the data, we compare it to analytically derived six-component polarization models that are valid for pure-state plane wave arrivals. For efficient classification, we make use of the supervised machine learning method of support vector machines that is trained using data-independent, analytically-derived six-component polarization models. This enables the rapid classification of seismic phases in a fully automated fashion, even for large data volumes, such as encountered in land-seismic exploration or ambient noise seismology. Once the wave-type is known, additional wave parameters (velocity, directionality, and ellipticity) can be directly extracted from the six-component polarization states without the need to resort to expensive optimization algorithms.We illustrate the benefits of our approach on various real and synthetic data examples for applications such as automated phase picking, aliased ground-roll suppression in land-seismic exploration, and the rapid close-to real time extraction of surface wave dispersion curves from single-station recordings of ambient noise. Additionally, we argue that an initial step of wave type classification is necessary in order to successfully apply the common technique of extracting phase velocities from combined measurements of rotational and translational motion.

Onboard optical-based autonomous navigation (autonav) has the potential to significantly reduce reliance on ground-based assets, and it can provide a robust backup system for unexpected ground outa...

We present a technique to automatically classify the wave type of seismic phases that are recorded on a single six-component recording station (measuring both three components of translational and rotational ground motion) at the Earth's surface. We make use of the fact that each wave type leaves a unique 'fingerprint' in the six-component motion of the sensor (i.e. the motion is unique for each wave type). This fingerprint can be extracted by performing an eigenanalysis of the data covariance matrix, similar to conventional three-component polarization analysis. To assign a wave type to the fingerprint extracted from the data, we compare it to analytically derived six-component polarization models that are valid for pure-state plane wave arrivals. For efficient classification, we make use of the supervised machine learning method of support vector machines that is trained using data-independent, analytically derived six-component polarization models. This enables the rapid classification of seismic phases in a fully automated fashion, even for large data volumes, such as encountered in land-seismic exploration or ambient noise seismology. Once the wave-type is known, additional wave parameters (velocity, directionality and ellipticity) can be directly extracted from the six-component polarization states without the need to resort to expensive optimization algorithms. We illustrate the benefits of our approach on various real and synthetic data examples for applications such as automated phase picking, aliased ground-roll suppression in land-seismic exploration and the rapid close-to real-time extraction of surface wave dispersion curves from single-station recordings of ambient noise. Additionally, we argue that an initial step of wave type classification is necessary in order to successfully apply the common technique of extracting phase velocities from combined measurements of rotational and translational motion., Geophysical Journal International, 234 (1), ISSN:0956-540X, ISSN:1365-246X

Aim Laparoscopic subtotal cholecystectomy is a safe strategy to avoid bile duct injury when a critical view of safety cannot be obtained. This technique may result in fewer open conversions and was introduced in our DGH in 2013. This study describes the change in practice at our centre following introduction of subtotal cholecystectomy. Method Retrospective case series included consecutive cholecystectomies over a ten-year period in a single institution. Cases were divided into subgroups based on operation date; 2009-2012 (Group A) and 2013-2019 (Group B). These groups represent pre- (Group A) and post- (Group B) introduction of laparoscopic subtotal cholecystectomy. Primary outcome was the proportion of patients undergoing laparoscopic total cholecystectomy, laparoscopic sub-total and lap-converted to open cholecystectomy. Secondary outcomes included incidence of bile leak, complication rate, return to theatre, and length of stay. Results There were 4248 cases; 1387 in Group A, and 2861 in Group B. The rate of open conversions was higher in Group A than Group B (4.7% vs. 2.8%, p = 0.003). The rate of laparoscopic total cholecystectomy was higher in Group A than Group B (95.3% vs. 92.8%, p = 0.013). In the subtotal group (n = 114, 3.9% of Group B); 14 (12.3%) patients had bile leak requiring ERCP, 6 (5.3%) underwent re-laparoscopy for inadequate biliary drainage, and median LOS was 2 days. Conclusion Laparoscopic subtotal cholecystectomy has proven to be a safe technique at our centre, reducing the rate of open conversion and length of stay, with a low rate of reintervention for bile leak.

Aims Gallbladder polyps are typically an incidental finding on sonographic or pathological examination with an estimated prevalence of 0.3 – 9.5%. Their role as a precursor to gallbladder malignancy is disputed. The 2017 European Joint Society Guidelines (ESGAR/EAES/EFISDS/ESGE) aim to standardise management of gallbladder polyps detected prior to cholecystectomy. We aim to describe our experience in the management of gallbladder polyps in a district general hospital. Methods This single centre retrospective case series included consecutive cholecystectomies over an 8-year period, identified through pathology records. Medical records were interrogated to identify the presence of gallbladder polyps identified pre-operatively and at subsequent histopathological analysis. Results 3835 cases were included. Four cases (0.1%) had an adenocarcinoma identified; none of these had pre-operatively identified polyps. Two cases (0.05%) were found to have lesions with high-grade dysplasia, 1 of which had a 17mm polyp preoperatively. One case (0.03%) had cellular atypia, without a pre-operative polyp. Forty six cases (1.2%) were found to have low-grade dysplasia; 1 (2.2%) of these had adenomyomatosis pre-operatively but none had pre-operative polyps. Overall, 53 patients (1.4%) had abnormal pathology with only 1 (1.9%) of these having a pre-operative polyp identified. Conclusions Our results suggest that in the real-world setting, intensive surveillance of gallbladder polyps has limited utility in identifying cases of gallbladder malignancy. The burden on services produced by adherence to strict surveillance guidelines is difficult to justify and a less arduous approach is unlikely to significantly influence the management or outcome in patients with gallbladder malignancy.

Aims Lower GI bleeding (LGIB) is a significant burden on healthcare resources with an estimated 21120 UK annual admissions. The Oakland score was developed in 2017 and allows patients to be triaged based on clinical and laboratory parameters to predict safe discharge; an Oakland score Methods This retrospective single centre study included 25 consecutive emergency LGIB referrals to a busy district general hospital. Oakland score was retrospectively calculated from case notes and clinical outcomes followed up. Results The average age of the patient group was 72.8 years, 56% were male. 64% of our patients were referred from ED with the remainder from GP. Mean Oakland score was 16.68. 40% of patients were on anti-platelets or a DOAC. The average length of stay was 2.56 days. 76% of these patients did not receive a blood transfusion and 73% did not undergo any imaging or endoscopy while an inpatient. Only 5 of the patients were sent home directly from the surgical assessment unit. Conclusions Our preliminary real world experience suggests that routine use of the Oakland score will allow for safe rationalisation of inpatient services. Further prospective data collection is required to validate this approach. Our data represents only patients admitted to hospital, therefore the low-scoring patient population is not represented; these patients will be included in prospective analysis.

Aim Acute appendicitis is the most common general surgical emergency. A recent consensus study has proposed a 10% negative appendicectomy rate. We aimed to determine the negative appendicectomy rate in our centre whilst evaluating the role of biomarkers in predicting the severity of appendicitis. Methods A single-centre retrospective analysis of consecutive laparoscopic appendicectomies from 2019-2020 was performed. Patients were categorised by severity using AAST grading system. Kruskal-Wallis test was used to compare biomarkers levels (WCC, CRP, bilirubin, neutrophil:lymphocyte ratio (NLR) and platelet:lymphocyte ratio (PLR)). T-test, ROC curve and Fisher’s exact test were used to differentiate between perforated and non-perforated appendicitis and negative appendicectomy rate. WCC ≥11, CRP ≥50, bilirubin ≥21, NLR ≥6.4 and PLR ≥153 were the cut-off values. Negative appendicitis was defined as normal appendix at histopathological analysis. Results 224 patients were included; mean age 33.7 years, 57.1% were male. 17 patients (7.6%) had negative appendicectomy. CRP, NLR, bilirubin and PLR increase with AAST score (P WCC (p = 0.018), CRP (p Conclusion 7.6% negative appendicectomy rate in our centre is below the recommended standard of 10% and lower than other centres. In our centre, raised WCC and NLR were predictive of acute appendicitis. WCC, CRP, bilirubin, NLR and PLR may be used to distinguish between perforated and non-perforated appendicitis. Our results add to the conflicting body of evidence relating to biomarkers and the severity of appendicitis.

Aims Sarcopenia is a multisystem disorder which can be diagnosed clinically and radiologically. It is associated with impaired functional status and inferior perioperative outcomes, in particular increased mortality following emergency laparotomy. This study aimed to show whether sarcopenia, as defined by low psoas muscle area (PMA) on pre-operative CT, was associated with increased need for stoma formation. Methods A retrospective analysis of consecutive emergency general surgical laparotomies over a 3-year period. PMA was measured on a single pre-operative CT image at L3 and normalized to vertebral body area to create a psoas muscle index (PMI). New stoma formation and perioperative outcomes were recorded from patient records. Cases were split by the median value into high “non-sarcopenic” and low “sarcopenic” PMI groups. Results 299 patients underwent emergency laparotomy between 01/01/2016 and 31/12/2018. 46 patients (30.67%) in the low psoas index group required a stoma compared with 37 (24.83%) in the higher group (p = 0.159). Survival was inferior in the sarcopenic group with a mean survival of 42 months compared to 48 months in the non-sarcopenic group (p = 0.032). Median follow-up was 43 months. Patients in the sarcopenic group were significantly older (Mean age 68 compared to 54 in the non-sarcopenic group, p = Conclusions Sarcopenia does not significantly increase the risk of requiring a stoma during emergency laparotomy but does reduce survival.

Background During the initial stages of the COVID-19 pandemic non-emergency endoscopy was suspended as per BSG recommendations, resulting in altered pathways for investigation of suspected malignancies. In our unit, patients referred via suspected colorectal cancer (CRC) pathways with a quantitative faecal immunochemical test (qFIT) >400 µg/g were offered CT imaging in the first instance. Methods We accessed our electronic records to retrospectively identify patients referred with a qFIT >400 µg/g between March and May 2020. Patient demographics, previous medical history, and referral details were recorded. Primary outcome was incidence of new CRC diagnosis. Results 21 patients were included. Median follow-up was 218 days, and median time from referral to CT was 17 days. 3 (14.3%) patients had new cancer diagnoses;2 CRC and 1 lung. 42.8% of patients had normal investigations, or benign colorectal pathology. 95.2% patients went on to have an endoscopy; low risk polyps (28.6%), high risk polyps (4.8%) and IBD (9.6%) were identified. 57.1% of patients were discharged following endoscopy, with the remaining 42.9% needing further management which included referral to other specialties and repeat scopes. Discussion and conclusion CT scanning did not reduce the need for subsequent endoscopy, but aided in prioritising patients for subsequent investigation. There were no cases of CRC identified endoscopically which were not identified by CT imaging. In conclusion, CT is a viable alternative to endoscopy when restrictions are placed on endoscopy services.

NASA’s Deep Space 1 mission demonstrated that a spacecraft can be navigated autonomously during deep-space cruise operations using only optical navigation measurements. A methodology is developed t...

The numerous books of the poet Al Purdy (1918–2000) are well known to readers of modern Canadian literature. His extensive archives conceal many unnoticed works, however, and the true extent of his literary career can only be seen when the unpublished writing is brought into view. A manuscript from the early 1960s – “Yehl the Raven and Other Creation Myths of the Haida” – illustrates the importance of the archives to studies of his life and works. The obscure sequence of poems demonstrates Purdy’s ethnographic interests and represents a point of contact between modern Canadian literature and mid-century anthropology. It also shows Purdy to have been engaged, for a time, in a manner of writing that was largely distinct from the autobiographical, anecdotal mode that typifies the poetry on which his reputation rests. He wrote his “Creation Myths” by adapting narratives found in the studies of Marius Barbeau (1883–1969), the Canadian folklorist and ethnographer. He attempted to publish the resultant poems as a short book, but “Yehl the Raven” never appeared in print, and although the manuscript has not been utterly invisible to Purdy’s colleagues and critics, it has been mischaracterized, unappreciated, and essentially overlooked. Nor have its origins and virtual disappearance yet been explained. This brief essay consequently examines the manuscript and suggests why it merits critical attention.

Graphical Abstract This online structured survey has demonstrated the global impact of the COVID-19 pandemic on vascular services. The majority of centres have documented marked reductions in operating and services provided to vascular patients. In the months during recovery from the resource restrictions imposed during the pandemic peaks, there will be a significant vascular disease burden awaiting surgeons. Graphical Abstract One of the most affected specialties

Citizen-driven Renewable Energy (RE) projects of various kinds, known collectively as community energy (CE), have an important part to play in the worldwide transition to cleaner energy systems. On the basis of evidence from 8 European countries, we investigate CE, over approximately the last 50 years (c.1970–2018), through the lens of Social Innovation (SI). We carry out a detailed review of literature around the social dimension of renewable energy; we collect, describe and map CE initiatives from Belgium, France, Germany, Italy, Poland, Spain, Sweden, and the UK; and we unpack the SI concept into 4 operational criteria which we suggest are essential to recognizing SI in CE. These are: (1) Crises and opportunities; (2) the agency of civil society; (3) reconfiguration of social practices, institutions and networks; (4) new ways of working. We identify three main phases of SI in CE. The environmental movements of the 1960s and the “oil shocks” of the 1970s provided the catalyst for a series of innovative societal responses around energy and self-sufficiency. A second wave of SI relates to the mainstreaming of RE and associated government support mechanisms. In this phase, with some important exceptions, successful CE initiatives were mainly confined to those countries where they were already embedded as innovators in the previous phase. The third phase of CE innovation relates to the societal response to the Great Recession that began in 2008 and lasted most of the subsequent decade. CE initiatives formed around this time were also strongly focused around democratization of energy and citizen empowerment in the context of rising energy prices, a weak economy, and a production and supply system dominated by excessively powerful multinational energy firms. CE initiatives today are more diverse than at any time previously, and are likely to continue to act as incubators for pioneering initiatives addressing virtually all aspects of energy. However, large multinational energy firms remain the dominant vehicle for delivery of the energy transition, and the apparent excitement in European policy circles for “community energy” does not extend to democratization of energy or genuine empowerment of citizens.

A method is introduced to transition space trajectories from low fidelity patched conics models to full-ephemeris n-body dynamics. The algorithm incorporates a continuation method that progressively re-converges solution trajectories in systems with incremental changes in the dynamics. Continuation is accomplished through the variation of a control parameter, which is tied to body ephemeris locations and masses, minimum flyby altitudes, and sphere of influence sizes. The intermediate models provide a continuous and differentiable path between solutions in the simplified and n-body dynamics, and the boundary values of the control parameter replicate the patched conics and full-ephemeris models exactly. Each successive step preserves the qualitative properties of the initial guess by successively altering flyby states and body masses. A similar approach to this methodology may be taken with any simplified starting guess, such as a restricted three-body model. Trajectories computed using the patched conics conversion method presented here may include gravity assists and rendezvous with any number of target bodies, so the method is ideal for constructing interplanetary or intermoon tour missions, and is amenable to patching shorter segments together to form longer tours.

A method is presented to calculate optimal trajectories to near-Earth asteroids that incorporate free-return trajectory segments. These trajectories are useful because they return to Earth with no fuel penalty, which is useful for risk mitigation on manned missions. The algorithm minimizes total velocity change over an entire nominal mission, encompassing a single impulsive maneuver each for Earth departure, leaving the free-return trajectory, rendezvous with and departure from the asteroid, culminating with unpowered reentry into Earth’s atmosphere. Two example cases are presented in the circular restricted three-body model: a mission to 2000 SG344 from 23 August 2028 to 9 October 2029 with a cost of 5.307 km/s, and a mission to 2006 BZ147 from 9 February 2033 to 21 December 2033 with a cost of 7.000 km/s. The results presented here showcase the usage of the algorithm, which may be applied to free-return trajectories to a wide variety of near-Earth objects.