Surgical management of chest injuries in patients with multiple and/or severe trauma- a systematic review and clinical practice guideline update.

PURPOSE: Our aim was to update evidence-based and consensus-based recommendations for the surgical and interventional management of blunt or penetrating injuries to the chest in patients with multiple and/or severe injuries on the basis of current evidence. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries. METHODS: MEDLINE and Embase were systematically searched to May and June 2021 respectively for the update and new questions. Further literature reports were obtained from clinical experts. Randomised controlled trials, prospective cohort studies, cross-sectional studies and comparative registry studies were included if they compared interventions for the surgical management of injuries to the chest in patients with multiple and/or severe injuries. We considered patient-relevant clinical outcomes such as mortality, length of stay, and diagnostic test accuracy. Risk of bias was assessed using NICE 2012 checklists. The evidence was synthesised narratively, and expert consensus was used to develop recommendations and determine their strength. RESULTS: One study was identified. This study compared wedge resection, lobectomy and pneumonectomy in the management of patients with severe chest trauma that required some form of lung resection. Based on the updated evidence and expert consensus, one recommendation was modified and two additional good practice points were developed. All achieved strong consensus. The recommendation on the amount of blood loss that is used as an indication for surgical intervention in patients with chest injuries was modified to reflect new findings in trauma care and patient stabilisation. The new good clinical practice points (GPPs) on the use of video-assisted thoracoscopic surgery (VATS) in patients with initial circulatory stability are also in line with current practice in patient care. CONCLUSION: As has been shown in recent decades, the treatment of chest trauma has become less and less invasive for the patient as diagnostic and technical possibilities have expanded. Examples include interventional stenting of aortic injuries, video-assisted thoracoscopy and parenchyma-sparing treatment of lung injuries. These less invasive treatment concepts reduce morbidity and mortality in the primary surgical phase following a chest trauma.

Quality of recovery after day care surgery with app-controlled remote monitoring: study protocol for a randomized controlled trial.

BACKGROUND: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. METHODS: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. DISCUSSION: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. TRIAL REGISTRATION: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772).

Sputum smear-positive, culture-negative state during anti-tuberculosis treatment in the MGIT liquid culture era.

The sputum smear-positive, culture-negative state poses a challenge for clinicians. Previous studies have shown that most samples with positive smears during the later stages of treatment are culture-negative. Earlier studies generally used solid culture media, which tend to be less sensitive than current liquid culture systems. We examined the smear-positive, culture-negative state in the era of MGIT™ 960™ liquid cultures. We found that the smear-positive, culture-negative state occurred less frequently with MGIT culture, and that the majority of the samples with late positive smears were culture-negative, regardless of media type.

Peri-operative management of patients with type-2 diabetes mellitus undergoing non-cardiac surgery using liraglutide, glucose-insulin-potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial.

In this open-label multicentre randomised controlled trial, we investigated three peri-operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18-75 years with type-2 diabetes mellitus undergoing non-cardiac surgery. Patients were randomly allocated using a web-based randomisation program to premedication with liraglutide (liraglutide group), glucose-insulin-potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l-1 . The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention-to-treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6-7.7 [4.2-13.5]) mmol.l-1 vs. 7.5 (6.4-8.3 [3.9-16.6]) mmol.l-1 (p = 0.026) and 7.6 (6.4-8.9 [4.7-13.2]) mmol.l-1 ) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre-operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre-operative administration of liraglutide stabilised peri-operative plasma glucose levels and reduced peri-operative insulin requirements, at the expense of increased pre-operative nausea rates.

Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-ß Signaling.

Aneurysm-osteoarthritis syndrome characterized by unpredictable aortic aneurysm formation, is caused by SMAD3 mutations. SMAD3 is part of the SMAD2/3/4 transcription factor, essential for TGF-ß-activated transcription. Although TGF-ß-related gene mutations result in aneurysms, the underlying mechanism is unknown. Here, we examined aneurysm formation and progression in Smad3-/- animals. Smad3-/- animals developed aortic aneurysms rapidly, resulting in premature death. Aortic wall immunohistochemistry showed no increase in extracellular matrix and collagen accumulation, nor loss of vascular smooth muscle cells (VSMCs) but instead revealed medial elastin disruption and adventitial inflammation. Remarkably, matrix metalloproteases (MMPs) were not activated in VSMCs, but rather specifically in inflammatory areas. Although Smad3-/- aortas showed increased nuclear pSmad2 and pErk, indicating TGF-ß receptor activation, downstream TGF-ß-activated target genes were not upregulated. Increased pSmad2 and pErk staining in pre-aneurysmal Smad3-/- aortas implied that aortic damage and TGF-ß receptor-activated signaling precede aortic inflammation. Finally, impaired downstream TGF-ß activated transcription resulted in increased Smad3-/- VSMC proliferation. Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-ß signaling, immune suppression may be more beneficial.

Reader variability and validation of the Timika X-ray score during treatment of pulmonary tuberculosis.

SETTING: Chest radiographs (CXRs) are widely used for diagnosing pulmonary TB and assessing response to therapy. The Timika X-ray score has been proposed as a tool for measuring disease severity and predicting treatment outcome. OBJECTIVE: To evaluate inter- and intra-reader agreement of Timika scores and assess the ability of the score to predict microbiologic outcome at 2 months. DESIGN: Analytical validation study. Disease severity was measured by two readers using pretreatment radiographs and follow-up films taken at 2, 6 and 12 months after the start of treatment among 110 human immunodeficiency virus negative adults with pulmonary TB. One fourth of the films were reread to assess intra-reader agreement. RESULTS: The two-component Timika score had high inter- and intra-reader agreement (intraclass correlation (ICC)inter = 75%, ICCintra > 0.81). Baseline Timika score was associated with positive month 2 smear (P = 0.0004) and culture status (P = 0.03). The average Timika score declined significantly over the course of successful treatment. CONCLUSION: The Timika score showed good inter- and intra-reader agreement and a significant association with microbiological outcomes after 2 months of treatment. The results of this study strengthen the evidence supporting the use of the Timika score for measuring disease severity on CXR.

Differential gene expression of activating Fcγ receptor classifies active tuberculosis regardless of human immunodeficiency virus status or ethnicity.

New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings.

Comparison of time to positive and colony counting in an early bactericidal activity study of anti-tuberculosis treatment.

SETTING: Patients with smear-positive, newly diagnosed pulmonary tuberculosis (TB) presenting to the out-patient TB clinic in Kampala, Uganda. OBJECTIVE: To compare colony-forming unit (cfu) counting and time to positive (TTP) in Mycobacteria Growth Indicator Tube (MGIT) culture as measures of early bactericidal activity (EBA). DESIGN: Patients were enrolled in an EBA feasibility study of standard TB chemotherapy. Sixteen-hour overnight sputum collections were obtained before and on days 2, 4, 7, 10, 12 and 14 of treatment for quantitative culture on selective Middlebrook 7H11 agar media and TTP in the MGIT liquid culture system. RESULTS: Log cfu and TTP were correlated over all time points (r(s) = -0.71, P < 0.001). Within-subject (day to day) variation as a percentage of total variation was very similar between the two measures: 25.7% for cfu and 25% for TTP. Mean EBA 0-14, 0-2 and 2-14 measured by TTP were similar to those previously reported. CONCLUSION: TTP measured by an automated, standardized, commercially available culture system correlates with cfu determinations. EBA measured by TTP provides similar information to cfu counting, and is reproducible across sites and in different patient populations. These findings support replacing cfu counting with TTP as the primary measurement in EBA studies.

Clinical symptoms and microbiological outcomes in tuberculosis treatment trials.

During a recent Food and Drug Administration workshop on clinical trials to evaluate new TB drugs, questions were raised regarding the use of bacteriologic endpoints such as treatment failure and relapse as measures of improvement in health status and long term outcome after treatment. FDA scientists asked how patients' clinical signs and symptoms changed during therapy, noting that while such information is usually collected during clinical trials, it is not often reported. We analyzed data from an international phase 3 TB treatment trial that included systematic assessments of symptoms. The percentage of subjects with self-reported symptoms at baseline ranged from 30% for dyspnea to 81% for cough, with 51% reporting fever. During therapy, fever, sweats, and dyspnea decreased most rapidly, with near resolution by the end of therapy. Chest pain and cough resolved more slowly; 13% of subjects reported cough at six months. Symptom resolution during treatment did not differ between those who relapsed and those who did not. Among those with microbiological relapse, symptoms returned with significant increases in the proportion with fever, cough, and chest pain. At the time of relapse, cough was the most frequent symptom, occurring in 75% of subjects who relapsed but only 12% of those who did not. Our data support the continued use of bacteriologic endpoints based on sputum culture as surrogate measures of the relief of symptoms, improvement in health status and favorable long term treatment outcome in TB drug trials.

Time to detection of Mycobacterium tuberculosis as an alternative to quantitative cultures.

Testing new drugs is critical to improving the treatment of tuberculosis. Quantitative cultures of Mycobacterium tuberculosis on solid media have been used in Phase 1 and 2 trials, but are time and resource intensive. Time to detection (TTD) of growth of M. tuberculosis in automated liquid culture systems is an alternative. TTD has been shown to correlate with CFU in quantitative cultures, and is faster and simpler to perform. We compared TTD in the BACTEC 460 liquid culture system with CFU in a clinical trial that included 110 subjects. Comparing all sputum cultures collected between baseline and 2 months we found a strong negative correlation between log(10) CFU and TTD (rho = -0.91). In addition, when TTD at baseline was compared with 1 and 2 month sputum culture positivity, subjects whose cultures were negative after 1 and 2 months had a significantly longer median baseline TTD compared with subjects whose cultures were positive at 1 and 2 months (5 vs. 3 days and 3 vs. 2 days, respectively). TTD compares closely with CFU and represents a faster, simpler alternative to quantitative cultures.

Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation.

Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV-1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)-6, IL-8, interferon (IFN)-γ and transforming growth factor (TGF)-ß, and did not include other T helper type 1 (Th1) (IL-2, IL-15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL-6 and IL-8, less with TGF-ß, and not with IFN-γ. Among CD4 T cells, FoxP3-reactive CD25(hi) were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3(+) CD25(hi) CD4 T cells were positive for IL-8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV-1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL-6, IL-8, IFN-γ and TGF-ß and regulatory T cells (T(reg) ). A correlation in expansion of T(reg) with proinflammatory cytokines (IL-6 and IL-8) in pleural fluid was shown. T(reg) themselves may promote the inflammatory cytokine milieu through IL-8.

Age and long-term protective immunity in dogs and cats.

Vaccination can provide an immune response that is similar in duration to that following a natural infection. In general, adaptive immunity to viruses develops earliest and is highly effective. Such anti-viral immune responses often result in the development of sterile immunity and the duration of immunity (DOI) is often lifelong. In contrast, adaptive immunity to bacteria, fungi or parasites develops more slowly and the DOI is generally short compared with most systemic viral infections. Sterile immunity to these infectious agents is less commonly engendered. Old dogs and cats rarely die from vaccine-preventable infectious disease, especially when they have been vaccinated and immunized as young adults (i.e. between 16 weeks and 1 year of age). However, young animals do die, often because vaccines were either not given or not given at an appropriate age (e.g. too early in life in the presence of maternally derived antibody [MDA]). More animals need to be vaccinated to increase herd (population) immunity. The present study examines the DOI for core viral vaccines in dogs that had not been revaccinated for as long as 9 years. These animals had serum antibody to canine distemper virus (CDV), canine parvovirus type 2 (CPV-2) and canine adenovirus type-1 (CAV-1) at levels considered protective and when challenged with these viruses, the dogs resisted infection and/or disease. Thus, even a single dose of modified live virus (MLV) canine core vaccines (against CDV, cav-2 and cpv-2) or MLV feline core vaccines (against feline parvovirus [FPV], feline calicivirus [FCV] and feline herpesvirus [FHV]), when administered at 16 weeks or older, could provide long-term immunity in a very high percentage of animals, while also increasing herd immunity.

[Vaginal prolapse and rectal obstruction. Treated with a vaginal vault mesh colpo suspension and laparoscopic resection rectopexy]. / Vaginalprolaps und Defäkationsobstruktion. Kombination einer Netzkolposuspension mit der laparoskopischen Resektionsrektopexie.

BACKGROUND: Stool outlet obstruction with incomplete or complete rectal prolapse combined with vaginal vault prolapse is a severe form of pelvic floor insufficiency. Combining laparoscopic resection rectopexy with a vaginal vault mesh colpo suspension is a possible way of correcting this defect. METHOD: The safety of the combination was evaluated in 18 patients. RESULTS: The procedure was performed successfully with no complications in 16 of the 18 patients. One patient suffered intraoperative rectal injury and therefore received no polypropylene mesh, and one showed intraoperative bleeding requiring transfusion. No secondary surgery was required. Hospital stay lasted an average of 11.4 days (range 8-20) and the urinary catheters could be removed after an average of 4.3 days (range 2-10). No urinary disturbances were noted at the time of hospital release. Short-term mild fever appeared in 28% of cases (5/18). There were two urinary tract infections. No disturbance in healing and no anastomotic insufficiency were observed. The duration of postoperative antibiotic therapy averaged 3 days (range 0-8). CONCLUSION: The combination of laparoscopic resection rectopexy with a vaginal vault mesh colpo suspension might be safe. The close contact between the mesh and anastomosis might induce no increase in insufficiency. Long-term outcome must still be evaluated.

Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable.

[New systems of mapping and navigation in electrophysiology]. / Nouveaux systèmes de cartographie et de navigation en électrophysiologie.

The indications of radiofrequency ablation of arrhythmias have considerably increased since the introduction of the technique in the early 1990s. Interventional rhythmologists now treat arrhythmias which are more and more complex by their mechanism. This requires accurate representation of the ablation catheter position and the integration of spatial and temporal data to identify the arrhythmogenic substrate. The systems of mapping and navigation developed over the last ten years are important tools for interventional rhythmologists. They are very useful for the identification of complex arrhythmogenic substrates which require "individualised" ablations in specific cases. The aim of this article is to review different systems of mapping, and/or navigation currently on the market and their principal characteristics without entering into the details of their use in interventional electrophysiology.

Interpretation of secondary electron images obtained using a low vacuum SEM.

Charging of insulators in a variable pressure environment was investigated in the context of secondary electron (SE) image formation. Sample charging and ionized gas molecules present in a low vacuum specimen chamber can give rise to SE image contrast. "Charge-induced" SE contrast reflects lateral variations in the charge state of a sample caused by electron irradiation during and prior to image acquisition. This contrast corresponds to SE emission current alterations produced by sub-surface charge deposited by the electron beam. "Ion-induced" contrast results from spatial inhomogeneities in the extent of SE signal inhibition caused by ions in the gaseous environment of a low vacuum scanning electron microscope (SEM). The inhomogeneities are caused by ion focusing onto regions of a sample that correspond to local minima in the magnitude of the surface potential (generated by sub-surface trapped charge), or topographic asperities. The two types of contrast exhibit characteristic dependencies on microscope operating parameters such as scan speed, beam current, gas pressure, detector bias and working distance. These dependencies, explained in terms of the behavior of the gaseous environment and sample charging, can serve as a basis for a correct interpretation of SE images obtained using a low vacuum SEM.

Correlation between electrogram morphology and standard criteria to validate bidirectional cavotricuspid block in common atrial flutter ablation.

AIM: Assessment of a bidirectional conduction block within the cavotricuspid isthmus (CTI) is critical during radiofrequency (RF) atrial flutter (AF) ablation. We investigated the use of bipolar atrial electrogram (BAE) morphology as an additional criterion identifying CTI block and tested it against two recognized criteria: differential pacing and reversal of the right atrial depolarization sequence during coronary sinus (CS) pacing. METHODS AND RESULTS: An RF ablation procedure was performed during 600 ms CS pacing in 100 consecutive patients with a common AF. BAE recorded along the CTI were continuously monitored. CTI conduction block was achieved by RF ablation in all patients and a clear change in BAE polarity in the Electrogram recorded by the dipoles located on the CTI and immediately lateral to the intended line of block (RS to QR pattern) associated with a confirmed CTI conduction block was observed in all cases. BAE morphology changes predicted bidirectional CTI conduction blocks with a 100% positive and a 100% negative predictive value. At a mean follow-up of 33 +/- 11 months, there was a 5% AF recurrence rate. CONCLUSIONS: Our study suggests that morphological changes in BAE recorded at sites lateral and adjacent to the target line of block may be used as a unique and robust criterion to validate CTI conduction block during AF ablation procedure.

Quantitative trait loci on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18 control variation in levels of T and B lymphocyte subpopulations.

Lymphocyte subpopulation levels are used for prognosis and monitoring of a variety of human diseases, especially those with an infectious etiology. As a primary step to defining the major gene variation underlying these phenotypes, we conducted the first whole-genome screen for quantitative variation in lymphocyte count, CD4 T cell, CD8 T cell, B cell, and natural killer cell numbers, as well as CD4:CD8 ratio. The screen was performed in 15 of the CEPH families that form the main human genome genetic project mapping resource. Quantitative-trait loci (QTLs) that account for significant proportions of the phenotypic variance of lymphocyte subpopulations were detected on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18. The most significant QTL found was for CD4 levels on chromosome 8 (empirical P=.00005). Two regions of chromosome 4 showed significant linkage to CD4:CD8 ratio (empirical P=.00007 and P=.003). A QTL for the highly correlated measures of CD4 and CD19 levels colocalized at 18q21 (both P=.003). Similarly, a shared region of chromosome 1 was linked to CD8 and CD19 levels (P=.0001 and P=.002, respectively). Several of the identified chromosome regions are likely to harbor polymorphic candidate genes responsible for these important human phenotypes. Their discovery has important implications for understanding the generation of the immune repertoire and understanding immune-system homeostasis. More generally, these data show the power of an integrated human gene-mapping approach for heritable molecular phenotypes, using large pedigrees that have been extensively genotyped.

On the role of electron-ion recombination in low vacuum scanning electron microscopy.

Here we demonstrate the effects of electron-ion recombination on imaging signals utilized in low vacuum scanning electron microscopes (SEMs). The presented results show that, under normal operating conditions, recombination of ionized gas molecules with secondary electrons (SEs) suppresses a significant fraction of emitted electrons. If the ion flux (and hence the spatial dependence of the SE-ion recombination rate) is laterally inhomogeneous across the imaged region of a specimen, contrast in SE images can be influenced and in some cases (under conditions of high detector field strength and long ionic mean free path) dominated by variations in the recombination rate. Consequently, SE images of features such as topographic asperities can exhibit edge-darkening, leading to inversion of some topographic contrast. Recognition of the extent and nature of electron-ion recombination is required for a correct understanding of processes occurring in variable pressure SEMs and, subsequently, for models of image formation.

Consequences of positive ions upon imaging in low vacuum scanning electron microscopy.

The effects caused by an excess quantity of ionized gas molecules within the low vacuum, variable pressure and environmental scanning electron microscope (ESEM) are described with reference to mechanisms by which they can influence imaging conditions. These effects can include specimen charging, recombination and development of space charge. They are demonstrated for three different classes of sample: (1) an electrically grounded conductor, (2) an electrically floating conductor, and (3) an electrical insulator. A new device is presented that will aid excess charge removal within the ESEM and help correct for some of these effects, thereby dramatically improving imaging over a wide range of operating conditions and samples. The mechanism of image enhancement is demonstrated with reference to the three classes of sample described above.