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OBJECTIVES: This study aimed to provide new insights into the impact of emergency department (ED) to ICU time on hospital mortality, stratifying patients by academic and nonacademic teaching (NACT) hospitals, and considering Acute Physiology and Chronic Health Evaluation (APACHE)-IV probability and ED-triage scores. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective cohort study (2009-2020) using data from the Dutch National Intensive Care Evaluation registry. Patients directly admitted from the ED to the ICU were included from four academic and eight NACT hospitals. Odds ratios (ORs) for mortality associated with ED-to-ICU time were estimated using multivariable regression, both crude and after adjusting for and stratifying by APACHE-IV probability and ED-triage scores. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 28,455 patients were included. The median ED-to-ICU time was 1.9 hours (interquartile range, 1.2-3.1 hr). No overall association was observed between ED-to-ICU time and hospital mortality after adjusting for APACHE-IV probability (p = 0.36). For patients with an APACHE-IV probability greater than 55.4% (highest quintile) and an ED-to-ICU time greater than 3.4 hours the adjusted OR (ORsadjApache) was 1.24 (95% CI, 1.00-1.54; p < 0.05) as compared with the reference category (< 1.1 hr). In the academic hospitals, the ORsadjApache for ED-to-ICU times of 1.6-2.3, 2.3-3.4, and greater than 3.4 hours were 1.21 (1.01-1.46), 1.21 (1.00-1.46), and 1.34 (1.10-1.64), respectively. In NACT hospitals, no association was observed (p = 0.07). Subsequently, ORs were adjusted for ED-triage score (ORsadjED). In the academic hospitals the ORsadjED for ED-to-ICU times greater than 3.4 hours was 0.98 (0.81-1.19), no overall association was observed (p = 0.08). In NACT hospitals, all time-ascending quintiles had ORsadjED values of less than 1.0 (p < 0.01). CONCLUSIONS: In patients with the highest APACHE-IV probability at academic hospitals, a prolonged ED-to-ICU time was associated with increased hospital mortality. We found no significant or consistent unfavorable association in lower APACHE-IV probability groups and NACT hospitals. The association between longer ED-to-ICU time and higher mortality was not found after adjustment and stratification for ED-triage score.

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Instability of the distal radioulnar joint and scapholunate dissociation may cause pain, functional impairment and subsequent arthrosis. There is no consensus about whether these injuries should be treated acutely in patients undergoing surgery for distal radial fractures. We conducted a prospective cohort study to determine whether concomitant distal radioulnar joint instability or scapholunate dissociation negatively influence patient-related outcomes in these patients. The primary outcome was the patient-reported wrist/hand evaluation at 6 and 12 months after surgery. Out of 62 patients, 58% and 27% had intraoperative distal radioulnar joint instability and scapholunate dissociation, respectively. No significant differences were found in patient-reported scores at follow-up between patients with stable and unstable distal radioulnar joints, nor between patients with and without scapholunate dissociation. Sixty-three per cent of patients with an unstable distal radioulnar joint during surgery were stable on retesting after 6 months. Our study suggests that a wait-and-see policy in these patients therefore seems reasonable.Level of evidence: III.

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PURPOSE: Severely burned patients are at risk for intra-abdominal hypertension (IAH) and associated complications such as organ failure, abdominal compartment syndrome (ACS), and death. The aim of this study was to determine the prevalence of IAH among severely burned patients. The secondary aim was to determine the value of urinary intestinal fatty acid binding protein (I-FABP) as early marker for IAH-associated complications. METHODS: A prospective observational study was performed in two burn centers in the Netherlands. Fifty-eight patients with burn injuries ≥ 15% of total body surface area (TBSA) were included. Intra-abdominal pressure (IAP) and urinary I-FABP, measured every 6 h during 72 h. Prevalence of IAH, new organ failure and ACS, and the value of urinary intestinal fatty acid binding protein (I-FABP) as early marker for IAH-associated complications were determined. RESULTS: Thirty-one (53%) patients developed IAH, 17 (29%) patients developed new organ failure, but no patients developed ACS. Patients had burns of 29% (P25-P75 19-42%) TBSA. Ln-transformed levels of urinary I-FABP and IAP were inversely correlated with an estimate of - 0.06 (95% CI - 0.10 to - 0.02; p = 0.002). Maximal urinary I-FABP levels had a fair discriminatory ability for patients with IAH with an area under the ROC curve of 74% (p = 0.001). Urinary I-FABP levels had no predictive value for IAH or new organ failure in severe burn patients. CONCLUSIONS: The prevalence of IAH among patients with ≥ 15% TBSA burned was 53%. None of the patients developed ACS. A relevant diagnostic or predictive value of I-FABP levels in identifying patients at risk for IAH-related complications, could not be demonstrated. LEVEL OF EVIDENCE: Level III, epidemiologic and diagnostic prospective observational study.

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PURPOSE: Where multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio of ~2. However, limited availability of "clinical truth sets" and prior use in tool training limits their utility for evaluation of tool performance. METHODS: We created a truth set of 9,436 missense variants classified as deleterious or tolerated in clinically validated high-throughput functional assays for BRCA1, BRCA2, MSH2, PTEN, and TP53 to evaluate predictive performance for 44 recommended/commonly used in silico tools. RESULTS: Over two-thirds of the tool-threshold combinations examined had specificity of <50%, thus substantially overcalling deleteriousness. REVEL scores of 0.8-1.0 had a Positive Likelihood Ratio (PLR) of 6.74 (5.24-8.82) compared to scores <0.7 and scores of 0-0.4 had a Negative Likelihood Ratio (NLR) of 34.3 (31.5-37.3) compared to scores of >0.7. For Meta-SNP, the equivalent PLR = 42.9 (14.4-406) and NLR = 19.4 (15.6-24.9). CONCLUSION: Against these clinically validated "functional truth sets," there was wide variation in the predictive performance of commonly used in silico tools. Overall, REVEL and Meta-SNP had best balanced accuracy and might potentially be used at stronger evidence weighting than current ACMG/AMP prescription, in particular for predictions of benignity.

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Hamate fractures can be treated nonoperatively, with the percutaneous Kirschner wire (K-wire) fixation, or with excision of a fractured hook of the hamate. Screw fixation is less popular owing to the risk of iatrogenic ulnar nerve injury. The aim of this study was to present the functional results of patients with hamate fractures treated with headless compression screws (HCS). The primary outcome was the Michigan Hand Outcome Questionnaire (MHOQ) after at least 4 months of follow-up. Nine patients were included in this retrospective cohort study. A median MHOQ total score of 67% was reported (interquartile range [IQR]: 44-76). No complications were found during follow-up. HCS fixation is a safe alternative to treat hamate fractures with good functional outcome. This is a Level IV study.

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OBJECTIVES: Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. METHODS: We evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. RESULTS: After adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04-1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. CONCLUSIONS: Using a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

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The aim of this study was to determine the difference in functional outcomes after open reduction and internal fixation (ORIF) with and without arthroscopic debridement in adults with displaced intra-articular distal radius fractures. In this multicentre trial, 50 patients were randomized between ORIF with or without arthroscopic debridement. The primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) score. Secondary outcome measures were Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, pain scores, range of wrist motion, grip strength, and complications. Median PRWE was worse for the intervention group at 3 months and was equal for both groups at 12 months. The secondary outcome measures did not show consistent patterns of differences at different time-points of follow-up. We conclude that patients treated with additional arthroscopy to remove intra-articular hematoma and debris did not have better outcomes than those treated with ORIF alone. We therefore do not recommend arthroscopy for removal of hematoma and debris when surgically fixing distal radius fractures. Level of evidence: I.

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Background Distal radius fractures in children are normally treated by plaster immobilization. For displaced unstable distal radius fractures, closed reduction and Kirschner wire (k-wire) fixation can be performed. Disadvantages of k-wire fixation are the need for postoperative plaster treatment for several weeks, which may induce stiffness, and the risks of complications such as tendon irritation and pin-track infections. More invasive volar plate fixation is less popular, although this allows for direct mobilization and enhances anatomical reduction. Purpose To present the functional outcomes of pediatric patients treated with volar plate fixation for unstable displaced distal radius fractures. Patients and Methods A retrospective cohort study of all consecutive pediatric patients between September 2010 and July 2017 was performed. A total of 26 patients with a median age of 12.5 years were included. The primary objective was functional outcome determined by the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Secondary objectives were range of motion, grip strength, radiological parameters, complications, and incidence of plate removal. Results Median PRWE score was 3 after a median follow-up of 29 months. Range of motion and grip strength did not differ significantly between the injured and uninjured wrists. No wound infections were found. Plate removal was performed in 15 patients (58%). Conclusion Volar plate fixation for unstable displaced distal radius fractures in children provides good functional and radiological outcomes with minor complications. Level of evidence This is a Level IV cohort study.

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PURPOSE: Mortality in burn intensive care unit (ICU) has been decreasing and treatment appears to be changing. The aims of this study: (1) examine outcome in burn patients, (2) examine changes in ICU indication and (3) explore the influence of a changing case-mix. METHODS: Retrospective study in patients admitted to ICU (1987-2016). Four groups were specified: major burns (≥15% TBSA), inhalation injury with small injury (<15% TBSA, inhalation injury), watchful waiting (<15% TBSA, without inhalation injury), tender loving care (patients withheld from treatment). Logistic regression was performed to evaluate the relation between case-mix and outcome. RESULTS: Overall mortality decreased to 7%. Mortality of major burns decreased by 15%. The major burn group decreased by 36%. The inhalation injury and watchful waiting group increased by 9% and 21%. The percentage of ventilated patients increased by 14% in the major burn group. 40% of patients were ventilated in the watchful waiting group. CONCLUSIONS: After correction for case-mix, survival improved, mainly in the major burn group. Case-mix shifted towards inhalation injury and watchful waiting. Growth of the watchful waiting group is not necessarily harmful. However, the increase of mechanical ventilation could be. We suggest raising awareness for risks and consequences of mechanical ventilation.

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Dengue virus (DENV) causes a profound burden of morbidity and mortality, and its global burden is rising due to the co-circulation of four divergent DENV serotypes in the ecological context of globalization, travel, climate change, urbanization, and expansion of the geographic range of the Ae.aegypti and Ae.albopictus vectors. Understanding DENV evolution offers valuable opportunities to enhance surveillance and response to DENV epidemics via advances in RNA virus sequencing, bioinformatics, phylogenetic and other computational biology methods. Here we provide a scoping overview of the evolution and molecular epidemiology of DENV and the range of ways that evolutionary analyses can be applied as a public health tool against this arboviral pathogen.

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BACKGROUND: In the past several years, an increase in open reduction and internal fixation (ORIF) for intra-articular distal radius fractures has been observed. This technique leads to a quicker recovery of function compared to non-operative treatment. However, some patients continue to have a painful and stiff wrist postoperatively. Arthroscopically assisted removal of intra-articular fracture haematoma and debris may improve the functional outcomes following operative treatment of intra-articular distal radius fractures. The purpose of this randomised controlled trial is to determine the difference in functional outcome, assessed with the Patient-Rated Wrist Evaluation (PRWE) score, after ORIF with and without an additional wrist arthroscopy in adult patients with displaced complete articular distal radius fractures. METHODS: In this multicentre trial, adult patients with a displaced complete articular distal radius fracture are randomised between ORIF with an additional wrist arthroscopy to remove fracture haematoma and debris (intervention group) and conventional fluoroscopic-assisted ORIF (control group). The primary outcome is functional outcome assessed with the PRWE score after three months. Secondary outcomes are wrist function assessed with the Disability of the Arm, Shoulder and Hand (DASH) score, postoperative pain, range of motion, grip strength, complications and cost-effectiveness. Additionally, in the intervention group, the quality of reduction, associated ligamentous injuries and cartilage damage will be assessed. A total of 50 patients will be included in this study. DISCUSSION: Although ORIF of intra-articular distal radius fractures leads to a quicker resume of function compared to non-operative treatment, some patients continue to have a painful and stiff wrist postoperatively. We hypothesise that, due to the removal of fracture haematoma and debris by an additional arthroscopy, functional outcomes will be better compared to the non-arthroscopically treated group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660515 . Registered on 13 January 2016.

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The aim of this study was to determine the relationship between volar plate removal and the Soong classification following fixation for fractured distal radius. In this retrospective cohort study, all consecutive patients who had volar plate fixation for a distal radius fracture in 2011-2015 were reviewed. Differences in Soong classification between patients who had plate removal and those who did not were analysed. The total incidence of plate removal was calculated and the indications analysed. A total of 323 patients were included. The incidence of plate removal in all patients was 17%. Soong classification was significantly higher in patients who had plate removal compared with those who did not. For patients with plate placement classified as Soong grade 2, the incidence of plate removal was almost six times higher than those classified as Soong grade 0. The relationship between volar plate removal and a higher Soong grading stresses the importance of accurate plate positioning. LEVEL OF EVIDENCE: IV.

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BACKGROUND: Unstable ankle fractures require treatment with open reduction and internal fixation (ORIF). Long-term functional outcome is satisfying in most patients; however, a number of patients have persistent complaints. Superficial nerve complications following ankle surgery may be the cause of chronic pain and disability. METHODS: In this observational retrospective survey, a cohort of 527 women and men, who underwent ORIF in the period from January 2007 to January 2014, were invited to an online questionnaire. Pain symptoms were assessed using the McGill Pain Questionnaire (MPQ) and the Douleur Neuropathic en 4 Questions (DN4) Questionnaire. Descriptive statistics were used to present patient characteristics; a logistic regression model was used to analyze prognostic factors of neuropathic pain. A total of 271 patients completed the questionnaire. Mean follow-up period was 5.8 years (±1.9). RESULTS: Persistent neuropathic pain symptoms were present in 61 of all patients, and 51 of these patients reported an impaired quality of life caused by their symptoms. In univariate analysis, the following parameters were associated with neuropathic pain: age, hypertension, a thyroid disorder, lower back pain, fracture dislocations, and late complications such as nonunion, posttraumatic arthritis, or osteochondral injury. In multivariate analysis, an age between 40 and 60 years was found to be a significant predictor of neuropathic pain. Hypertension, dislocation, and late complications were significant predictors of persistent pain without neuropathic characteristics. CONCLUSION: The present study demonstrated a prevalence of persistent neuropathic pain symptoms after ORIF for ankle fractures in 23% of the respondents, which caused an impaired health-related quality of life. We identified 4 significant predictors of chronic and neuropathic pain after ORIF. This knowledge may aid the treating surgeon to identify patients who are at increased risk of persistent postoperative neuropathic pain and may affect the treatment of pain in these patients. LEVEL OF EVIDENCE: Level IV, retrospective case series.

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BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure. About 20% of implanted patients are considered as "non-responders". This study aimed to evaluate gated myocardial perfusion single-photon emission computed tomography (GMPS) phase parameters as compared to echocardiography in the assessment of predictors for response to CRT before and after CRT activation. METHODS: Forty-two patients were prospectively included during 15 months. A single injection of 99mTc-tetrofosmin was used to acquire GMPS phase pre- and post-CRT activation. Indicators of positive CRT response were improvement of functional status and 15% reduction in left ventricular end-systolic volume at 3 months. RESULTS: Phase parameters at baseline were similar in the two groups with no influence of perfusion data. Phase parameters after CRT activation were significantly improved in the responders' group (Δ Bandwidth -19° ± 24° vs. 13° ± 31°, p = 0.001; Δ SD -20° ± 30° vs. 26° ± 46°, p = 0.001; Δ Entropy -11 ± 12 vs. 2 ± 6%, p = 0.001). Feasibility and reproducibility were higher for GMPS. CONCLUSION: Acute phase modifications after CRT activation may predict response to CRT immediately after implantation, but not at baseline, even when adjusted to perfusion data.

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Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo sapiens-tc/THA/2014/SV0127-14 and Zika virus/H. sapiens-tc/PHL/2012/CPC-0740, isolated from the blood of patients collected in Thailand, 2014, and the Philippines, 2012, respectively. Sequencing and phylogenetic analysis showed that both strains belong to the Asian lineage.

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OBJECTIVE: To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. METHODS: Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was tend; MR acquisitions performed at tend-2M, tend-4M and tend-6M (respectively 2, 4 and 6 months before tend) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∆B from tend-4M to tend-2M and ∆B from tend-6M to tend-4M. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. RESULTS: The fraction of hypoperfused tumor volume (F_hPg) was a relevant biomarker. A ratio R(F_hPg) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (≥0.61) was associated with more relapse at tend compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). CONCLUSION: Iterative analysis of F_hPg from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. KEY POINTS: • Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. • Biomarkers were assessed through their patterns of variation during the follow-up. • The fraction of hypoperfused tumour volume (F_hP g ) seemed to be a relevant biomarker. • An innovative ratio R(F_hP g ) could be an early surrogate marker of relapse. • A significant time gain could be achieved in the management of GBM patients.

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There is an increasing role for bioinformatic and phylogenetic analysis in tropical medicine research. However, scientists working in low- and middle-income regions may lack access to training opportunities in these methods. To help address this gap, a 5-day intensive bioinformatics workshop was offered in Lima, Peru. The syllabus is presented here for others who want to develop similar programs. To assess knowledge gained, a 20-point knowledge questionnaire was administered to participants (21 participants) before and after the workshop, covering topics on sequence quality control, alignment/formatting, database retrieval, models of evolution, sequence statistics, tree building, and results interpretation. Evolution/tree-building methods represented the lowest scoring domain at baseline and after the workshop. There was a considerable median gain in total knowledge scores (increase of 30%, p<0.001) with gains as high as 55%. A 5-day workshop model was effective in improving the pathogen-applied bioinformatics knowledge of scientists working in a middle-income country setting.

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The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm2. A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm2. The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm2. The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm2. Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm2 were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm2 and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.

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Nowadays MOSFET dosimeters are widely used for dose verification in radiotherapy procedures. Although their sensitive area satisfies size requirements for small field dosimetry, their use in radiosurgery has rarely been reported. The aim of this study is to propose and optimize a calibration method to perform surface measurements in 6 MV shaped-beam radiosurgery for field sizes down to 18 × 18 mm(2). The effect of different parameters such as recovery time between 2 readings, batch uniformity and build-up cap attenuation was studied. Batch uniformity was found to be within 2% and isocenter dose attenuation due to the build-up cap over the MOSFET was near 2% irrespective of field size. Two sets of sensitivity coefficients (SC) were determined for TN-502RD MOSFET dosimeters using experimental and calculated calibration; the latter being developed using an inverse square law model. Validation measurements were performed on a realistic head phantom in irregular fields. MOSFET dose values obtained by applying either measured or calculated SC were compared. For calibration, optimal results were obtained for an inter-measurement time lapse of 5 min. We also found that fitting the SC values with the inverse square law reduced the number of measurements required for calibration. The study demonstrated that combining inverse square law and Sterling-Worthley formula resulted in an underestimation of up to 4% of the dose measured by MOSFETs for complex beam geometries. With the inverse square law, it is possible to reduce the number of measurements required for calibration for multiple field-SSD combinations. Our results suggested that MOSFETs are suitable sensors for dosimetry when used at the surface in shaped-beam radiosurgery down to 18 × 18 mm(2).

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BACKGROUND: As a result of increasing numbers of patients with morbid obesity there is a worldwide demand for bariatric surgeons. The Roux-en-Y gastric bypass, nowadays performed mostly laparoscopically (LRYGB), has been proven to be a highly effective surgical treatment for morbid obesity. This procedure is technically demanding and requires a long learning curve. Little is known about implementing these demanding techniques in the training of the surgical resident. The aim of this study was to evaluate the safety and feasibility of the introduction of LRYGB into the training of surgical residents. METHODS: All patients who underwent LRYGB between March 2006 and July 2010 were retrospectively analyzed. The procedure was performed by a surgical resident under strict supervision of a bariatric surgeon (group I) or by a bariatric surgeon (group II). The primary end point was the occurrence of complications. Secondary end points included operative time, days of hospitalization, rate of readmission, and reappearance in the emergency department (ED) within 30 days. RESULTS: A total of 409 patients were found eligible for inclusion in the study: 83 patients in group I and 326 in group II. There was a significant difference in operating time (129 min in group I vs. 116 min in group II; p < 0.001) and days of hospitalization. Postoperative complication rate, reappearance in the ED, and rate of readmission did not differ between the two groups. CONCLUSIONS: Our data suggest that under stringent supervision and with sufficient laparoscopic practice, implementation of LRYGB as part of surgical training is safe and results in only a slightly longer operating time. Complication rates, days of hospitalization, and the rates of readmission and reappearance in the ED within 30 days were similar between the both groups. These results should be interpreted by remembering that all procedures in group I were performed in a training environment so occasional intervention by a bariatric surgeon, when necessary, was inevitable.

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