Rapid rise in COVID-19 among young people in England - learning for the future.

OBJECTIVES: We determined the age and sociodemographic distribution of COVID-19 cases between January and September 2020 to identify the group with the highest incidence rates at the beginning of the second wave in England. STUDY DESIGN: We undertook a retrospective cohort study design. METHODS: SARS-CoV-2 cases in England were linked with area-level socio-economic status indicators using quintiles of the Index of Multiple Deprivation (IMD). Age-specific incidence rates were stratified by IMD quintile to further assess rates by area-level socio-economic status. RESULTS: Between July and September 2020, SARS-CoV-2 incidence rates were highest amongst those aged 18-21 years, reaching rates of 213.9 (18-19 years) and 143.2 (20-21 years) per 100,000 population by week ending 21 September 2022. Stratification of incidence rates by IMD quintile evidenced that despite high rates observed in the most deprived areas of England amongst the very young and older age groups, the highest rates were observed in the most affluent areas of England amongst the 18- to 21-year-olds. CONCLUSIONS: The reversal of sociodemographic trend in COVID-19 cases in England for those aged 18-21 years at the end of the summer of 2020 and beginning of the second wave showed a novel pattern of COVID-19 risk. For other age groups, the rates remained highest for those from more deprived areas, which highlighted persisting inequalities. Combined, this demonstrates the need to reinforce awareness of COVID-19 risk for young people, particularly given the late inclusion of the 16-17 years age group for vaccination administration, as well as continued efforts to reduce the impact of COVID-19 on vulnerable populations.

Abdominal wall pseudohernia - One secondary to a thoracic extraforaminal disc herniation and other due to thoracic paracentral disc protrusion.

An abdominal wall pseudohernia is a rare clinical entity which consists of an abnormal bulging of the abdominal wall that can resemble a true hernia, but without an associated underlying fascial or muscle defect. It is caused by segmental neuropathy and subsequent denervation of abdominal wall musculature. We present two cases of an abdominal wall pseudohernia. One secondary to a thoracic extraforaminal disc herniation in a 57-year-old male, which, as far as the authors are aware, has not been described previously. The other in a 67 year old male due to right foraminal and paracentral disc protrusion at T9/10.

Calcaneal offset index to measure hindfoot alignment in pes planus.

INTRODUCTION: Pes planus is a common three-dimensional (3D) deformity characterised by forefoot abduction, the collapse of the medial longitudinal arch, and hindfoot valgus. Several radiological measurements such as anteroposterior talocalcaneal angle (Kite's) and 'Calcaneal pitch angle' (CPA) exist to calculate the degree of hindfoot alignment in these patients with variable intra- and interobserver reliability. OBJECTIVE: To describe a new radiological ancillary method of measuring hindfoot alignment, the calcaneal offset index (COI). MATERIAL AND METHODS: Anteroposterior (mortise) and lateral view weight-bearing (WB) ankle radiographs of 200 consecutive patients referred for foot and ankle pain were reviewed. Demographic details, clinical indication, and COI calculation were undertaken on the mortise view along with the measurement of CPA for each patient. A one-way analysis of variance (ANOVA) was performed. Intraclass correlation coefficient (ICC) analysis was evaluated to assess the intraclass reliability between observers. RESULTS: There was a female preponderance of 2:1 in the study population with a mean age of 51.21 years (13-86 years). The calcaneal offset was increased in pes planus (hindfoot valgus). The p-value was 0.00023 on ANOVA. The COI gave an excellent interobserver correlation with ICC of 0.9 and moderate intraobserver reliability on the ICC analysis of 0.55. CONCLUSION: The COI can be an additional index of measuring hindfoot alignment in patients with pes planus. Contrary to the traditional angular measurements, this linear transverse plane measure is easier to calculate and reproducible. COI measurement has shown moderate intraobserver reliability but excellent interobserver reliability.

Clinical Implementation of Second-generation Minimally Invasive Image-guided Cochlear Implantation Surgery.

OBJECTIVE: Minimally invasive, image-guided cochlear implantation (CI) surgery consists of drilling a precise tunnel from the surface of the mastoid cortex through the facial recess to target the scala tympani. In the first set of clinical trials of this technique, heat-induced facial nerve paresis (House-Brackmann II/VI) occurred on a patient on the last day of the initial trial which was scheduled to be halted secondary to a change in the regulatory requirements dictated by the 2012 the Food and Drug Administration Safety and Innovation Act requiring Investigational Device Exemption approval for previously exempted customized medical device testing. To address this adverse event, extensive changes were made to the drilling protocol; additionally, a custom insertion tool was developed. To address the Food and Drug Administration Safety and Innovation Act, an Investigational Device Exemption was submitted and, subsequently approved. Herein is described our first clinical implementation of the modified technique. PATIENT: Seventy-year-old with profound, postlingual sensorineural hearing loss who had previously undergone right CI via traditional approach in 2015. INTERVENTION: Minimally invasive image-guided left CI. MAIN OUTCOME MEASURE: Time of intervention, final location of CI electrode array within cochlea. RESULTS: Surgery took 155 minutes of which the largest components (in descending order) were soft tissue work, closure, and drilling. Full scala tympani insertion with angular insertion depth of 557 degrees of the electrode array was achieved. There were no complications, and the patient had an uneventful recovery and activation. CONCLUSIONS: Minimally invasive, image-guided CI surgery is achievable and reduces the mastoid depression associated with traditional CI surgery. CLINICALTRIALSGOV INFORMATION: Study NCT03101917, Microtable Microstereotactic Frame and Drill Press and Associated Method for Cochlear Implantation. LEVEL OF EVIDENCE: Case Report.

Estimating the intensity of use by interacting predators and prey using camera traps.

Understanding how organisms distribute themselves in response to interacting species, ecosystems, climate, human development and time is fundamental to ecological study and practice. A measure to quantify the relationship among organisms and their environments is intensity of use: the rate of use of a specific resource in a defined unit of time. Estimating the intensity of use differs from estimating probabilities of occupancy or selection, which can remain constant even when the intensity of use varies. We describe a method to evaluate the intensity of use across conditions that vary in both space and time. We demonstrate its application on a large mammal community where linear developments and human activity are conjectured to influence the interactions between white-tailed deer (Odocoileus virginianus) and wolves (Canis lupus) with possible consequences on threatened woodland caribou (Rangifer tarandus caribou). We collect and quantify intensity of use data for multiple, interacting species with the goal of assessing management efficacy, including a habitat restoration strategy for linear developments. We test whether blocking linear developments by spreading logs across a 200-m interval can be applied as an immediate mitigation to reduce the intensities of use by humans, predator and prey species in a boreal caribou range. We deployed camera traps on linear developments with and without restoration treatments in a landscape exposed to both timber and oil development. We collected a three-year dataset and employed spatial recurrent event models to analyse intensity of use by an interacting human and large mammal community across a range of environmental and climatic conditions. Spatial recurrent event models revealed that intensity of use by humans influenced the intensity of use by all five large mammal species evaluated, and the intensities of use by wolves and deer were inextricably linked in space and time. Conditions that resist travel on linear developments had a strong negative effect on the intensity of human and large mammal use. Mitigation strategies that resist, or redirect, animal travel on linear developments can reduce the effects of resource development on interacting human and predator-prey interactions. Our approach is easily applied to other continuous time point-based survey methodologies and shows that measuring the intensity of use within animal communities can help scientists monitor, mitigate and understand ecological states and processes.

An evaluation of selected (Q)SARs/expert systems for predicting skin sensitisation potential.

Predictive testing to characterise substances for their skin sensitisation potential has historically been based on animal models such as the Local Lymph Node Assay (LLNA) and the Guinea Pig Maximisation Test (GPMT). In recent years, EU regulations, have provided a strong incentive to develop non-animal alternatives, such as expert systems software. Here we selected three different types of expert systems: VEGA (statistical), Derek Nexus (knowledge-based) and TIMES-SS (hybrid), and evaluated their performance using two large sets of animal data: one set of 1249 substances from eChemportal and a second set of 515 substances from NICEATM. A model was considered successful at predicting skin sensitisation potential if it had at least the same balanced accuracy as the LLNA and the GPMT had in predicting the other outcomes, which ranged from 79% to 86%. We found that the highest balanced accuracy of any of the expert systems evaluated was 65% when making global predictions. For substances within the domain of TIMES-SS, however, balanced accuracies for the two datasets were found to be 79% and 82%. In those cases where a chemical was within the TIMES-SS domain, the TIMES-SS skin sensitisation hazard prediction had the same confidence as the result from LLNA or GPMT.

Possible glimpses into early speciation: the effect of ovarian fluid on sperm velocity accords with post-copulatory isolation between two guppy populations.

Identifying mechanisms of reproductive isolation is key to understanding speciation. Among the putative mechanisms underlying reproductive isolation, sperm-female interactions (post-mating-prezygotic barriers) are arguably the hardest to identify, not least because these are likely to operate at the cellular or molecular level. Yet sperm-female interactions offer great potential to prevent the transfer of genetic information between different populations at the initial stages of speciation. Here, we provide a preliminary test for the presence of a putative post-mating-prezygotic barrier operating between three populations of Trinidadian guppies (Poecilia reticulata), an internally fertilizing fish that inhabits streams with different levels of connectivity across Trinidad. We experimentally evaluate the effect of female ovarian fluid on sperm velocity (a predictor of competitive fertilization success) according to whether males and females were from the same (native) or different (foreign) populations. Our results reveal the potential for ovarian fluid to act as a post-mating-prezygotic barrier between two populations from different drainages, but also that the strength of this barrier is different among populations. This result may explain the previous finding that, in some populations, sperm from native males have precedence over foreign sperm, which could eventually lead to reproductive isolation between these populations.

Workflow and simulation of image-to-physical registration of holes inside spongy bone.

PURPOSE: Mastoid cells as well as trabecula provide unique bone structures, which can serve as natural landmarks for registration. Preoperative imaging enables sufficient acquisition of these structures, but registration requires an intraoperative counterpart. Since versatile surgical interventions involve drilling into mastoid cells and trabecula, we propose a registration method based on endoscopy inside of these drill holes. METHODS: Recording of the surface of the inner drill hole yields bone-air patterns that provide intraoperative registration features. In this contribution, we discuss an approach that unrolls the drill hole surface into a two-dimensional image. Intraoperative endoscopic recordings are compared to simulated endoscopic views, which originate from preoperative data like computed tomography. Each simulated view corresponds to a different drill pose. The whole registration procedure and workflow is demonstrated, using high-resolution image data to simulate both preoperative and endoscopic image data. RESULTS: As the driving application is minimally invasive cochlear implantation, in which targets are close to the axis of the drill hole, Target Registration Error (TRE) was measured at points near the axis. TRE at increasing depths along the drill trajectory reveals increasing registration accuracy as more bone-air patterns become available as landmarks with the highest accuracy obtained at the center point. At the facial recess and the cochlea, TREs are ([Formula: see text]) mm and ([Formula: see text]) mm, respectively. CONCLUSION: This contribution demonstrates a new method for registration via endoscopic acquisition of small features like trabecula or mastoid cells for image-guided procedures. It has the potential to revolutionize bone registration because it requires only a preoperative dataset and intraoperative endoscopic exploration. Endoscopic recordings of at least 20 mm length and isotropic voxel sizes of 0.2 mm or smaller of the preoperative image data are recommended.

Application of IATA - A case study in evaluating the global and local performance of a Bayesian network model for skin sensitization.

The information characterizing key events in an Adverse Outcome Pathway (AOP) can be generated from in silico, in chemico, in vitro and in vivo approaches. Integration of this information and interpretation for decision making are known as integrated approaches to testing and assessment (IATA). One such IATA was published by Jaworska et al., which describes a Bayesian network model known as ITS-2. The current work evaluated the performance of ITS-2 using a stratified cross-validation approach. We also characterized the impact of replacing the most significant component of the network, output from the expert system TIMES-SS, with structural alert information from the OECD Toolbox and Toxtree. Lack of structural alerts or TIMES-SS predictions yielded a sensitization potential prediction of 79%. If the TIMES-SS prediction was replaced by a structural alert indicator, the network predictivity increased up to 87%. The original network's predictivity was 89%. The local applicability domain of the original ITS-2 network was also evaluated using reaction mechanistic domains to understand what types of chemicals ITS-2 was able to make the best predictions for. We found that the original network was successful at predicting which chemicals would be sensitizers, but not at predicting their potency.

The prognostic utility of the transcription factor SRF in docetaxel-resistant prostate cancer: in-vitro discovery and in-vivo validation.

BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel. Targeting these changes individually does not significantly impact on the resistant phenotype but understanding the central signalling pathways and transcription factors (TFs) which control these could represent a more appropriate therapeutic targeting approach. METHODS: Using a number of docetaxel-resistant sublines of PC-3 cells, we have undertaken a transcriptomic analysis by expression microarray using the Affymetrix Human Gene 1.0 ST Array and in conjunction with bioinformatic analyses undertook to predict dysregulated TFs in docetaxel resistant prostate cancer. The clinical significance of this prediction was ascertained by performing immunohistochemical (IHC) analysis of an identified TF (SRF) in the metastatic sites from men who died of advanced CRPC. Investigation of the functional role of SRF was examined by manipulating SRF using SiRNA in a docetaxel-resistant PC-3 cell line model. RESULTS: The transcription factors identified include serum response factor (SRF), nuclear factor kappa-B (NFκB), heat shock factor protein 1 (HSF1), testicular receptor 2 & 4 (TR2 &4), vitamin-D and retinoid x receptor (VDR-RXR) and oestrogen-receptor 1 (ESR1), which are predicted to be responsible for the differential gene expression observed in docetaxel-resistance. IHC analysis to quantify nuclear expression of the identified TF SRF correlates with both survival from date of bone metastasis (p = 0.003), survival from androgen independence (p = 0.00002), and overall survival from prostate cancer (p = 0.0044). Functional knockdown of SRF by siRNA demonstrated a reversal of apoptotic resistance to docetaxel treatment in the docetaxel-resistant PC-3 cell line model. CONCLUSIONS: Our results suggest that SRF could aid in treatment stratification of prostate cancer, and may also represent a therapeutic target in the treatment of men afflicted with advanced prostate cancer.

Estimating plant abundance using inflated beta distributions: Applied learnings from a lichen-caribou ecosystem.

Quantifying abundance and distribution of plant species can be difficult because data are often inflated with zero values due to rarity or absence from many ecosystems. Terrestrial fruticose lichens (Cladonia and Cetraria spp.) occupy a narrow ecological niche and have been linked to the diets of declining caribou and reindeer populations (Rangifer tarandus) across their global distribution, and conditions related to their abundance and distribution are not well understood. We attempted to measure effects related to the occupancy and abundance of terrestrial fruticose lichens by sampling and simultaneously modeling two discrete conditions: absence and abundance. We sampled the proportion cover of terrestrial lichens at 438 vegetation plots, including 98 plots having zero lichens. A zero-inflated beta regression model was employed to simultaneously estimate both the absence and the proportion cover of terrestrial fruticose lichens using fine resolution satellite imagery and light detection and ranging (LiDAR) derived covariates. The probability of lichen absence significantly increased with shallower groundwater, taller vegetation, and increased Sphagnum moss cover. Vegetation productivity, Sphagnum moss cover, and seasonal changes in photosynthetic capacity were negatively related to the abundances of terrestrial lichens. Inflated beta regression reliably estimated the abundance of terrestrial lichens (R2 = .74) which was interpolated on a map at fine resolution across a caribou range to support ecological conservation and reclamation. Results demonstrate that sampling for and simultaneously estimating both occupancy and abundance offer a powerful approach to improve statistical estimation and expand ecological inference in an applied setting. Learnings are broadly applicable to studying species that are rare, occupy narrow niches, or where the response variable is a proportion value containing zero or one, which is typical of vegetation cover data.

An evaluation of community-based cognitive stimulation therapy: a pilot study with an Irish population of people with dementia.

OBJECTIVES: Research shows that cognitive stimulation therapy (CST) improves cognitive function, quality of life, and well-being of people with mild-moderate dementia. Despite consistent evidence and recommendations, CST is not routinely available in Ireland post-diagnosis. The aim of the current research was to develop and evaluate community-based CST for people with mild-moderate dementia, run by the Alzheimer Society of Ireland across four pilot sites in Ireland. METHODS: Participants with mild-moderate dementia attended once weekly CST sessions for 14 weeks. Baseline and post-intervention assessments were completed by CST participants, carers, and CST facilitators. Primary outcomes of interest for CST participants included quality of life (Quality of Life in Alzheimer Disease Scale), cognitive function (Montreal Cognitive Assessment), and subjective cognitive function (Memory Awareness Rating Scale-Functioning Subscale). Secondary outcomes included well-being, cognitive ability, satisfaction with cognitive performance, and engagement and confidence of CST participants; well-being of carers; and job satisfaction of facilitators. Post-intervention interviews supplemented quantitative analyses. RESULTS: In total, 20 CST participants, 17 carers, and six CST facilitators completed evaluation assessments. Results showed that CST improved participants' satisfaction with cognitive performance (p=0.002), level of engagement (p=0.046), level of confidence (p=0.026). Improvements on subjective cognitive function just fell short of significance (p=0.055). Qualitative analysis of interview data identified consistent themes of cognitive and overall benefits of CST; and provided support for quantitative data. CONCLUSIONS: Community-based CST positively impacted the lives of people with dementia and their families. This study supports prior recommendations that CST should be made routinely available to people with mild-moderate dementia, particularly in light of the lack of post-diagnostic interventions currently offered in Ireland.

Safety margins in robotic bone milling: from registration uncertainty to statistically safe surgeries.

BACKGROUND: When robots mill bone near critical structures, safety margins are used to reduce the risk of accidental damage due to inaccurate registration. These margins are typically set heuristically with uniform thickness, which does not reflect the anisotropy and spatial variance of registration error. METHODS: A method is described to generate spatially varying safety margins around vital anatomy using statistical models of registration uncertainty. Numerical simulations are used to determine the margin geometry that matches a safety threshold specified by the surgeon. RESULTS: The algorithm was applied to CT scans of five temporal bones in the context of mastoidectomy, a common bone milling procedure in ear surgery that must approach vital nerves. Safety margins were generated that satisfied the specified safety levels in every case. CONCLUSIONS: Patient safety in image-guided surgery can be increased by incorporating statistical models of registration uncertainty in the generation of safety margins around vital anatomy.

Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging.

BACKGROUND: Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. AIM: To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. METHODS: Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. RESULTS: Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. CONCLUSIONS: This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use.

Endoscopic management of colonic perforations: clips versus suturing closure (with videos).

BACKGROUND AND AIMS: Perforation during colonoscopy remains the most worrisome adverse event and usually requires urgent surgical rescue. The aim of this study was to evaluate the feasibility and effectiveness of endoscopic closure of full-thickness colonic perforations. METHODS: We performed a retrospective analysis of all consecutive patients with endoscopically closed colonic perforations over the past 6 years (2009-2014). Colonic perforations were closed by using endoscopic clips or an endoscopic suturing device. Most patients were admitted for treatment with intravenous antibiotics and kept on bowel rest. If their clinical condition deteriorated, urgent surgery was performed. If patients remained stable, oral feeding was resumed, and patients were discharged with subsequent clinical and endoscopic follow-up. RESULTS: Twenty-one patients had iatrogenic colonic perforations closed with an endoscopic suturing device or endoscopic clips during the study period. Primary closure of a colonic perforation was performed with endoscopic clips in 5 patients and sutured with an endoscopic suturing device in 16 patients. All 5 patients after clip closure had worsening of abdominal pain and required laparoscopy (4 patients) or rescue colonoscopy with endoscopic suturing closure (1 patient). Two patients had abdominal pain after endoscopic suturing closure, but diagnostic laparoscopy confirmed complete and adequate endoscopic closure of the perforations. The other 15 patients did not require any rescue surgery or laparoscopy after endoscopic suturing. The main limitation of our study is its retrospective, single-center design and relatively small number of patients. CONCLUSION: Endoscopic suturing closure of colonic perforations is technically feasible, eliminates the need for rescue surgery, and appears more effective than closure with hemostatic endoscopic clips.

Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

Increasing Safety of a Robotic System for Inner Ear Surgery Using Probabilistic Error Modeling Near Vital Anatomy.

Safe and effective planning for robotic surgery that involves cutting or ablation of tissue must consider all potential sources of error when determining how close the tool may come to vital anatomy. A pre-operative plan that does not adequately consider potential deviations from ideal system behavior may lead to patient injury. Conversely, a plan that is overly conservative may result in ineffective or incomplete performance of the task. Thus, enforcing simple, uniform-thickness safety margins around vital anatomy is insufficient in the presence of spatially varying, anisotropic error. Prior work has used registration error to determine a variable-thickness safety margin around vital structures that must be approached during mastoidectomy but ultimately preserved. In this paper, these methods are extended to incorporate image distortion and physical robot errors, including kinematic errors and deflections of the robot. These additional sources of error are discussed and stochastic models for a bone-attached robot for otologic surgery are developed. An algorithm for generating appropriate safety margins based on a desired probability of preserving the underlying anatomical structure is presented. Simulations are performed on a CT scan of a cadaver head and safety margins are calculated around several critical structures for planning of a robotic mastoidectomy.

Prepared for Practice? Interns' Experiences of Undergraduate Clinical Skills Training in Ireland.

BACKGROUND: Many previous studies on internship have reported a lack of preparedness for the role. More recently in Ireland, medical schools have introduced formal clinical skills training programmes. This study sought to evaluate the impact, if any, of formal skills training in the medical training on intern's preparedness for practice. METHODS: The study utilized a survey approach followed by focus group discussions. The aim was to identify the skills that were taught and assessed in medical training and the skills that were actually required in their intern year. RESULTS: Most interns had received skills training in designated skills laboratories. No intern had received training in all skills advised in the European guidelines. Skills taught to all interns were intravenous cannulation, basic life support, and basic suture. Skills required from all interns were intravenous cannulation, phlebotomy, and arterial blood sampling. Removal of peripherally inserted central line (PICC) lines, central lines, and chest drains were commonly requested but not taught. Senior staff underestimated skill abilities and expected failure. CONCLUSION: These findings identify discordance between the skills taught and the skills required in the job. There is a need for standardization in the clinical skills training to ensure that all interns enter practice with equal competencies. Consideration should be given to experiential learning opportunities such as subintern programmes to consolidate learning and improve preparedness. Improvement in communications with senior clinicians is indicated to ensure that expectations are realistic and reflective of actual training.

Incorporating Target Registration Error Into Robotic Bone Milling.

Robots have been shown to be useful in assisting surgeons in a variety of bone drilling and milling procedures. Examples include commercial systems for joint repair or replacement surgeries, with in vitro feasibility recently shown for mastoidectomy. Typically, the robot is guided along a path planned on a CT image that has been registered to the physical anatomy in the operating room, which is in turn registered to the robot. The registrations often take advantage of the high accuracy of fiducial registration, but, because no real-world registration is perfect, the drill guided by the robot will inevitably deviate from its planned path. The extent of the deviation can vary from point to point along the path because of the spatial variation of target registration error. The allowable deviation can also vary spatially based on the necessary safety margin between the drill tip and various nearby anatomical structures along the path. Knowledge of the expected spatial distribution of registration error can be obtained from theoretical models or experimental measurements and used to modify the planned path. The objective of such modifications is to achieve desired probabilities for sparing specified structures. This approach has previously been studied for drilling straight holes but has not yet been generalized to milling procedures, such as mastoidectomy, in which cavities of more general shapes must be created. In this work, we present a general method for altering any path to achieve specified probabilities for any spatial arrangement of structures to be protected. We validate the method via numerical simulations in the context of mastoidectomy.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.