Adjuvant chemotherapy for resected duodenal adenocarcinoma: a case-matched analysis in nation wide cohort.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare tumor for which survival data on adjuvant chemotherapy in patients after surgical treatment are unclear. This case-matched study in a nationwide cohort aims to investigate the benefit of adjuvant chemotherapy for patients with resectable DA on overall survival. METHODS: All patients diagnosed with DA and intestinal type periampullary adenocarcinoma (PVA) in the Netherlands between 2000 and 2015 were included (n = 1316). Patients with disease stages II and III who underwent resection and adjuvant chemotherapy were matched (1:2), based on identified covariates associated with OS, with patients who underwent surgery alone. Overall survival was compared using Kaplan-Meier estimates. RESULTS: The median OS was 49.9 months in patients who underwent curative resection (n = 649). Univariate and multivariate analysis showed a significant influence of age, lymph node involvement, and T- stage on survival. The group of patients receiving adjuvant treatment consisted of 43 patients and the non-adjuvant group of 83 case-matched patients. The median OS of the complete matched cohort (n = 126) was 26.9 months. No statistically significant survival benefit was found for the adjuvant group as compared to the group treated with surgery alone (median OS = 34.4 months and 23.0 months, p = 0.20). CONCLUSION: This population-based, case-matched analysis demonstrates no statistically significant survival benefit for adjuvant chemotherapy after curative resection in stages II and III patients. Future studies with specified treatment regimens as well as thorough stratification for prognostic factors will be required in order to more definitively determine the role of adjuvant therapy.

Induction of labor with Foley catheter and risk of subsequent preterm birth: follow-up study of two randomized controlled trials (PROBAAT-1 and -2).

OBJECTIVE: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins. METHODS: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks' gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth < 37 weeks' gestation in a subsequent pregnancy. RESULTS: Fourteen hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow-up. In total, 251 and 258 women had a known subsequent pregnancy > 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38-2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30-3.51). CONCLUSION: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Attraction of mosquitoes to primate odours and implications for zoonotic Plasmodium transmission.

Vector-borne diseases often originate from wildlife and can spill over into the human population. One of the most important determinants of vector-borne disease transmission is the host preference of mosquitoes. Mosquitoes with a specialised host preference are guided by body odours to find their hosts in addition to carbon dioxide. Little is known about the role of mosquito host preference in the spillover of pathogenic agents from humans towards animals and vice versa. In the Republic of Congo, the attraction of mosquitoes to primate host odours was determined, as well as their possible role as malaria vectors, using odour-baited traps mimicking the potential hosts of mosquitoes. Most of the mosquito species caught showed a generalistic host preference. Anopheles obscurus was the most abundant Anopheles mosquito, with a generalistic host preference observed from the olfactory response and the detection of various Plasmodium parasites. Interestingly, Culex decens showed a much higher attraction towards chimpanzee odours than to human or cow odours. Human Plasmodium parasites were observed in both human and chimpanzee blood, although not in the Anopheles mosquitoes that were collected. Understanding the role of mosquito host preference for cross-species parasite transmission provides information that will help to determine the risk of spillover of vector-borne diseases.

Predictors of Continuous Positive Airway Pressure Adherence in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common disease which impacts quality of life, mood, cardiovascular morbidity, and mortality. Continuous positive airway pressure (CPAP) is the first-line treatment for patients with moderate to severe OSA. CPAP ameliorates respiratory disturbances, leading to improvements in daytime sleepiness, quality of life, blood pressure, and cognition. However, despite the high efficacy of this device, CPAP adherence is often sub-optimal. Factors including: socio-demographic/economic characteristics, disease severity, psychological factors, and side-effects are thought to affect CPAP adherence in OSA patients. Intervention studies have suggested that augmented support/education, behavioral therapy, telemedicine and technological interventions may improve CPAP adherence. In this paper, we will extensively review the most common factors including age, gender, race/ethnicity, socioeconomic status, smoking status, severity of OSA, severity of OSA symptoms, psychological variables, social support, marital status/bed partner involvement, dry nose and mouth, mask leak, and nasal congestion that may predict CPAP adherence. We will also extensively review interventions that may increase adherence to CPAP.

Sex Differences in White Matter Microstructure in the Human Brain Predominantly Reflect Differences in Sex Hormone Exposure.

Sex differences have been described regarding several aspects of human brain morphology; however, the exact biological mechanisms underlying these differences remain unclear in humans. Women with the complete androgen insensitivity syndrome (CAIS), who lack androgen action in the presence of a 46,XY karyotype, offer the unique opportunity to study isolated effects of sex hormones and sex chromosomes on human neural sexual differentiation. In the present study, we used diffusion tensor imaging to investigate white matter (WM) microstructure in 46,XY women with CAIS (n = 20), 46,XY comparison men (n = 30), and 46,XX comparison women (n = 30). Widespread sex differences in fractional anisotropy (FA), with higher FA in comparison men than in comparison women, were observed. Women with CAIS showed female-typical FA throughout extended WM regions, predominantly due to female-typical radial diffusivity. These findings indicate a predominant role of sex hormones in the sexual differentiation of WM microstructure, although sex chromosome genes and/or masculinizing androgen effects not mediated by the androgen receptor might also play a role.

The effect of fluid resuscitation on the effective circulating volume in patients undergoing liver surgery: a post-hoc analysis of a randomized controlled trial.

To assess the significance of an analogue of the mean systemic filling pressure (Pmsa) and its derived variables, in providing a physiology based discrimination between responders and non-responders to fluid resuscitation during liver surgery. A post-hoc analysis of data from 30 patients undergoing major hepatic surgery was performed. Patients received 15 ml kg-1 fluid in 30 min. Fluid responsiveness (FR) was defined as an increase of 20% or greater in cardiac index, measured by FloTrac-Vigileo®. Dynamic preload variables (pulse pressure variation and stroke volume variation: PPV, SVV) were recorded additionally. Pvr, the driving pressure for venous return (=Pmsa-central venous pressure) and heart performance (EH; Pvr/Pmsa) were calculated according to standard formula. Pmsa increased following fluid administration in responders (n = 18; from 13 ± 3 to 17 ± 4 mmHg, p < 0.01) and in non-responders (n = 12; from 14 ± 4 to 17 ± 4 mmHg, p < 0.01). Pvr, which was lower in responders before fluid administration (6 ± 1 vs. 7 ± 1 mmHg; p = 0.02), increased after fluid administration only in responders (from 6 ± 1 to 8 ± 1 mmHg; p < 0.01). EH only decreased in non-responders (from 0.56 ± 0.17 to 0.45 ± 0.12; p < 0.05). The area under the receiver operating characteristics curve of Pvr, PPV and SVV for predicting FR was 0.75, 0.73 and 0.72, respectively. Changes in Pmsa, Pvr and EH reflect changes in effective circulating volume and heart performance following fluid resuscitation, providing a physiologic discrimination between responders and non-responders. Also, Pvr predicts FR equivalently compared to PPV and SVV, and might therefore aid in predicting FR in case dynamic preload variables cannot be used.

MRI-based transfer function determination for the assessment of implant safety.

PURPOSE: We introduce a new MR-based method to determine the transfer function (TF) for radiofrequency (RF) safety assessment of active implantable medical devices. Transfer functions are implant-specific measures that relate the incident tangential electric field on an (elongated) implant to a scattered electric field at its tip. The proposed method allows for TF determination with a high spatial resolution in relatively fast measurements without requiring dedicated bench setups from MRI images. THEORY AND METHODS: The principle of reciprocity is used in conjunction with the potential to measure currents with MRI to determine TF. Low-flip angle 3D dual gradient echo MRI data are acquired with an implant as transceive antenna, which requires minimal hardware adaptations. The implant-specific TF is determined from the acquired MRI data, with two different postprocessing methods for comparison. RESULTS: TFs of linear and helical implants can be determined accurately (with a Pearson correlation coefficient R ≥ 0.7 between measurements and simulations, and a difference in field at the tip ΔEtip ≤ 19%) from relatively quick (t < 20 minutes) MRI acquisitions with (several) millimeter spatial resolution. CONCLUSION: Transfer function determination with MRI for RF safety assessment of implantable medical devices is possible. The proposed MR-based method allows for TF determination in more realistic exposure scenarios and solid media. Magn Reson Med 78:2449-2459, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Occupational skin diseases: actual state analysis of patient management pathways in 28 European countries.

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.

The repopulation of electronic states upon vibrational excitation of niobium carbide clusters.

We study the infrared (IR) resonant heating of neutral niobium carbide clusters probed through ultraviolet photoionization spectroscopy. The IR excitation not only changes the photoionization spectra for the photon energies above the ionization threshold, but also modulates ion yield for energies significantly below it. An attempt to describe the experimental spectra using either Fowler's theory or thermally populated vibrational states was not successful. However, the data can be fully modeled by vibrationally and rotationally broadened discrete electronic levels obtained from Density Functional Theory (DFT) calculations. The application of this method to spectra with different IR pulse energies not only yields information about the excited electronic states in the vicinity of the HOMO level, populated by manipulation of the vibrational coordinates of a cluster, but also can serve as an extra indicator for the cluster isomeric structure and corresponding DFT-calculated electronic levels.

Determination of the geometric structure of neutral niobium carbide clusters via infrared spectroscopy.

We report experimental vibrational spectra of small neutral niobium carbide clusters in the 350-850 cm-1 spectral range. Clusters were first irradiated by IR light and subsequently probed using UV light with photon energies just below the ionization threshold. Upon resonance with an IR vibrational mode, the number of cluster ions increases, allowing to record a vibrational spectrum. In complementary density functional theory calculations, we have simulated the IR spectra for several low-energy isomers. We were able to assign the spectra experimentally obtained for each cluster size to a specific geometric structure based on the match with the computed spectra. The number of the cluster sizes investigated here allows to follow the evolution of the geometric structure of the niobium and carbon components of clusters separately. For Nb6Cm (m = 4, 5, 6), we observe the emergence of the cubic crystal structures similar to the bulk.

Mitochondrial Neurogastrointestinal Encephalopathy: Clinical, Biochemical and Molecular Study in Three Egyptian Patients.

Background: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, biochemical and molecular findings in three Egyptian patients with Mitochondrial Neurogastrointestinal Encephalopathy sundrome from two different pedigrees. Subjects and Methods: The three patients were subjected to thorough neurologic examination. Brain Magtnetic Resonance Imaging. Histochemical and biochemical assay of the mitochondrial respiratory chain complexes in muscle homogenate was performed (1/3). Thymidine Phosphorylase enzyme activity was performed in 2/3 patients and Thymidine Phosphorylase gene sequencing was done (2/3) to confirm the diagnosis. Results: All patients presented with symptoms of severe gastrointestinal dysmotility with progressive cachexia, neuropathy, sensory neural hearing loss, asymptomatic leukoencephalopathy. Histochemical analysis of themuscle biopsy revealed deficient cytochrome C oxidase and mitochrondrial respiratory chain enzyme assay revealed isolated complex 1 deficiency (1/3). Thymidine Phosphorylase enzyme activity revealed complete absence of enzyme activity in 2/3 patients. Direct sequencing of Thymidine Phosphorylase gene revealed c.3371 A>C homozygous mutation. Molecular screening of both families revealed heterozygous mutation in both parents and 4 siblings. Conclusions: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare mitochondrial disorder with an important diagnostic delay. In case of pathogenic mutations in Thymidine Phosphorylase gene in the family, carrier testing and prenatal diagmosis of at risk members is recommended for early detection. The possibility of new therapeutic options makes it necessary to diagnose the disease in an early state.

Impact of the papillary muscles on cardiac magnetic resonance image analysis of important left ventricular parameters in hypertrophic cardiomyopathy.

PURPOSE: The use of cardiac magnetic resonance (CMR) analysis has increased in patients with hypertrophic cardiomyopathy (HCM). Quantification of left ventricular (LV) measures will be affected by the inclusion or exclusion of the papillary muscles as part of the LV mass, but the magnitude of effect and potential consequences are unknown. METHODS: We performed Cine-CMR in (1) clinical HCM patients (n = 55) and (2) subclinical HCM mutation carriers without hypertrophy (n = 14). Absolute and relative differences in LV ejection fraction (EF) and mass were assessed between algorithms with and without inclusion of the papillary muscles. RESULTS: Papillary muscle mass in group 1 was 6.6 ± 2.5 g/m(2) and inclusion of the papillary muscles resulted in significant relative increases in LVEF of 4.5 ± 1.8 % and in LV mass of 8.7 ± 2.6 %. For group 2 these figures were 4.0 ± 0.9 g/m(2), 3.8 ± 1.0 % and 9.5 ± 1.8 %, respectively. With a coefficient of variation of 4 %, this 9 % difference in LV mass during CMR follow-up will be considered a change, while in fact the exact same mass may have been assessed according to two different algorithms. CONCLUSIONS: In clinical HCM patients, CMR quantification of important LV measures is significantly affected by inclusion or exclusion of the papillary muscles. In relative terms, the difference was similar in subjects without hypertrophy. This underscores a general need for a uniform approach in CMR image analysis.

The don't know option in progress testing.

Formula scoring (FS) is the use of a don't know option (DKO) with subtraction of points for wrong answers. Its effect on construct validity and reliability of progress test scores, is subject of discussion. Choosing a DKO may not only be affected by knowledge level, but also by risk taking tendency, and may thus introduce construct-irrelevant variance into the knowledge measurement. On the other hand, FS may result in more reliable test scores. To evaluate the impact of FS on construct validity and reliability of progress test scores, a progress test for radiology residents was divided into two tests of 100 parallel items (A and B). Each test had a FS and a number-right (NR) version, A-FS, B-FS, A-NR, and B-NR. Participants (337) were randomly divided into two groups. One group took test A-FS followed by B-NR, and the second group test B-FS followed by A-NR. Evidence for impaired construct validity was sought in a hierarchical regression analysis by investigating how much of the participants' FS-score variance was explained by the DKO-score, compared to the contribution of the knowledge level (NR-score), while controlling for Group, Gender, and Training length. Cronbach's alpha was used to estimate NR and FS-score reliability per year group. NR score was found to explain 27 % of the variance of FS [F(1,332) = 219.2, p < 0.0005], DKO-score, and the interaction of DKO and Gender were found to explain 8 % [F(2,330) = 41.5, p < 0.0005], and the interaction of DKO and NR 1.6 % [F(1,329) = 16.6, p < 0.0005], supporting our hypothesis that FS introduces construct-irrelevant variance into the knowledge measurement. However, NR-scores showed considerably lower reliabilities than FS-scores (mean year-test group Cronbach's alphas were 0.62 and 0.74, respectively). Decisions about FS with progress tests should be a careful trade-off between systematic and random measurement error.

Regulation of skeletal muscle oxidative phenotype by classical NF-κB signalling.

BACKGROUND: Impairments in skeletal muscle oxidative phenotype (OXPHEN) have been linked to the development of insulin resistance, metabolic inflexibility and progression of the metabolic syndrome and have been associated with progressive disability in diseases associated with chronic systemic inflammation. We previously showed that the inflammatory cytokine tumour necrosis factor-α (TNF-α) directly impairs muscle OXPHEN but underlying molecular mechanisms remained unknown. Interestingly, the inflammatory signalling pathway classical nuclear factor-κB (NF-κB) is activated in muscle in abovementioned disorders. Therefore, we hypothesised that muscle activation of classical NF-κB signalling is sufficient and required for inflammation-induced impairment of muscle OXPHEN. METHODS: Myotubes from mouse and human muscle cell lines were subjected to activation or blockade of the classical NF-κB pathway. In addition, wild-type and MISR (muscle-specific inhibition of classical NF-κB) mice were injected intra-muscularly with TNF-α. Markers and key regulators of muscle OXPHEN were investigated. RESULTS: Classical NF-κB activation diminished expression of oxidative phosphorylation (OXPHOS) sub-units, slow myosin heavy chain expression, activity of mitochondrial enzymes and potently reduced intra-cellular ATP levels. Accordingly, PGC-1/PPAR/NRF-1/Tfam signalling, the main pathway controlling muscle OXPHEN, was impaired upon classical NF-κB activation which required intact p65 trans-activation domains and depended on de novo gene transcription. Unlike wild-type myotubes, IκBα-SR myotubes (blocked classical NF-κB signalling) were refractory to TNF-α-induced impairments in OXPHEN and its regulation by the PGC-1/PPAR/NRF-1/Tfam cascade. In line with in vitro data, NF-κB blockade in vivo abrogated TNF-α-induced reductions in PGC-1α expression. CONCLUSION: Classical NF-κB activation impairs skeletal muscle OXPHEN.

Prognostic value of Geriatric-8 for adverse outcomes within 30 days of surgery in older adults with colorectal cancer: A retrospective cohort study.

PURPOSE: It is unclear whether the Geriatric-8 (G8) has the accuracy to preselect patients for complete geriatric assessment, and has the ability to predict adverse outcomes in patients with colorectal cancer (CRC). We therefore aimed to determine whether the G8, or other variables present in the medical record, are applicable in predicting 30-day adverse outcomes in older patients undergoing surgery for CRC. METHODS: We performed a retrospective cohort study involving patients ≥70 years who had surgery for CRC between 2018 and 2020 in a general hospital in the Netherlands. The primary outcome was adverse outcome(s), which is a composite of surgical and non-surgical complications, readmission and mortality, all within 30 days of surgery. The secondary endpoints were the individual components, such as delirium, infection and ileus. We explored potential prognostic factors using multivariable logistic regression analysis. Data were collected from the Dutch ColoRectal Audit (DRCA) and medical records. RESULTS: The study included 200 patients (mean age 78.9 years: 50% female), with 36.5% having adverse outcomes in the first 30 days of surgery. In neither univariate nor multivariable analysis were G8 scores associated with adverse outcomes. Factors with higher odds of adverse outcomes were male gender, and having cognitive decline or previous delirium. CONCLUSION: This study confirms that G8 scores have no prognostic value for adverse outcomes, complications and mortality within 30 days of surgery among older adults with CRC. Therefore, the G8 should not be the tool for short-term risk prediction of adverse outcomes in these patients.

Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial.

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

BACKGROUND: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality. OBJECTIVE: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access. PATIENTS AND METHODS: Exposure equivalent dosing strategies were developed based on pharmacokinetic modeling and simulation by using the published pharmacokinetic model developed by the license holder. The alternative dose was based on the principle of using complete vials to prevent spillage and on the established non-linear relationship between body weight and systemic exposure. Equivalent exposure compared to the approved dosing regimen of 10 mg/kg was aimed for. Equivalent exposure was conservatively defined as calculated geometric mean ratios within the 0.9-1.11 boundaries for area under the concentration-time curve (AUC), trough concentration (Ctrough) and maximum concentration (Cmax) of the alternative dosing regimen compared to the approved dosing regimen. Since different vial sizes are available for the European Union (EU) and United States (US) market, because body weight distributions differ between these populations, we performed our analysis for both scenarios. RESULTS: Dosing regimens of sacituzumab govitecan for the EU (< 50 kg: 400 mg, 50-80 kg: 600 mg, and > 80 kg: 800 mg) and US population (< 40 kg: 360 mg, 40-65 kg: 540 mg, 65-90 kg: 720 mg, and > 90 kg: 900 mg) were developed, based on weight bands. The geometric mean ratios for all pharmacokinetic outcomes were within the predefined equivalence boundaries, while the quantity of drug used was 21.5% and 19.0% lower for the EU and US scenarios, respectively. CONCLUSIONS: With the alternative dosing proposal, an approximately 20% reduction in drug expenses for sacituzumab govitecan can be realized while maintaining an equivalent and more evenly distributed exposure throughout the body weight range, without notable increases in pharmacokinetic variability.

Risk of infection and sepsis in severely injured patients related to single nucleotide polymorphisms in the lectin pathway.

BACKGROUND: Infectious complications remain a serious threat to patients with multiple trauma. Susceptibility and response to infection is, in part, heritable. The lectin pathway plays a major role in innate immunity. The aim of this study was to assess whether single nucleotide polymorphisms (SNPs) in three key genes within the lectin pathway affect susceptibility to infectious complications in severely injured patients. METHODS: A prospective cohort of severely injured patients admitted to a level I trauma centre between January 2008 and April 2011 were genotyped for SNPs in MBL2 (mannose-binding lectin 2), MASP2 (MBL-associated serine protease 2) and FCN2 (ficolin 2). Association of genotype with prevalence of positive culture findings and infection was tested by χ(2) and logistic regression analysis. RESULTS: A total of 219 patients were included, of whom 112 (51·1 per cent) developed a positive culture from sputum, wounds, blood or urine. A systemic inflammatory response syndrome (SIRS) developed in 139 patients (63·5 per cent), sepsis in 79 (36·1 per cent) and septic shock in 37 (16·9 per cent). Patients with a MBL2 exon 1 variant allele were more prone to positive wound cultures (odds ratio (OR) 2·51, 95 per cent confidence interval 1·12 to 5·62; P = 0·025). A MASP2 Y371D DD genotype predisposed to SIRS (OR 4·78, 1·06 to 21·59; P = 0·042) and septic shock (OR 2·53, 1·12 to 4·33; P = 0·003). A FCN2 A258S AS genotype predisposed to positive wound cultures (OR 3·37, 1·45 to 7·85; P = 0·005) and septic shock (OR 2·18, 1·30 to 4·78; P = 0·011). CONCLUSION: Severely injured patients with SNPs in MBL2, MASP2 Y371D and FCN2 A258S of the lectin pathway of complement activation are significantly more susceptible to positive culture findings, and to infectious complications, SIRS and septic shock than patients with a wildtype genotype.

Single-size thermometric measurements on a size distribution of neutral fullerenes.

We present measurements of the velocity distribution of electrons emitted from mass-selected neutral fullerenes, performed at the intracavity free electron laser FELICE. We make use of mass-specific vibrational resonances in the infrared domain to selectively heat up one out of a distribution of several fullerene species. Efficient energy redistribution leads to decay via thermionic emission. Time-resolved electron kinetic energy distributions measured give information on the decay rate of the selected fullerene. This method is generally applicable to all neutral species that exhibit thermionic emission and provides a unique tool to study the stability of mass-selected neutral clusters and molecules that are only available as part of a size distribution.