Structural evolution in Au- and Pd-based metallic glass forming liquids and the case for improved molecular dynamics force fields.

The results of a combined experimental and computational investigation of the structural evolution of Au81Si19, Pd82Si18, and Pd77Cu6Si17 metallic glass forming liquids are presented. Electrostatically levitated metallic liquids are prepared, and synchrotron x-ray scattering studies are combined with embedded atom method molecular dynamics simulations to probe the distribution of relevant structural units. Metal-metalloid based metallic glass forming systems are an extremely important class of materials with varied glass forming ability and mechanical processibility. High quality experimental x-ray scattering data are in poor agreement with the data from the molecular dynamics simulations, demonstrating the need for improved interatomic potentials. The first peak in the x-ray static structure factor in Pd77Cu6Si17 displays evidence for a Curie-Weiss type behavior but also a peak in the effective Curie temperature. A proposed order parameter distinguishing glass forming ability, 1/ST,q1-1, shows a peak in the effective Curie temperature near a crossover temperature established by the behavior of the viscosity, TA.

Breakdown of the Stokes-Einstein relationship and rapid structural ordering in CuZrAl metallic glass-forming liquids.

The results of a combined structural and dynamical study of Cu-Zr-Al metallic glass forming liquids are presented. Containerless high-energy x-ray scattering experiments made using electrostatic levitation are combined with molecular dynamics simulations to probe the onset of rapid structural ordering as well as the temperature-dependent diffusivity and viscosity in three liquids: Cu49Zr45Al6, Cu47Zr45Al8, and Cu43Zr45Al12. These compositions were chosen because they are reported to have dramatically different glass forming-ability. Experimental data show that the first peak in the x-ray static structure factor displays evidence for a Curie-Weiss type behavior, but also a peak in the effective Curie temperature. The evidence provided here for the onset of cooperativity, marked by a crossover temperature, TA (which is usually above the liquidus temperature), is accompanied by the onset of development of more spatially extended structural order in the liquids. Based on the molecular dynamics simulations, each of the liquids exhibits a clear breakdown of the Stokes-Einstein relation at a temperature near, but below, the crossover temperature, TA. The breakdown is manifest as a rapid reduction in the relative diffusion coefficients between Cu, Zr, and Al.

All naturally occurring autoantibodies against the NMDA receptor subunit NR1 have pathogenic potential irrespective of epitope and immunoglobulin class.

Autoantibodies of the IgG class against N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) were first described in anti-NMDAR encephalitis and seen as disease indicators. Recent work on together over 5000 individuals challenged this exclusive view by showing age-dependently up to >20% NMDAR1-autoantibody seroprevalence with comparable immunoglobulin class and titer distribution across health and disease. The key question therefore is to understand the properties of these autoantibodies, also in healthy carriers, in order to assess secondary complications and possible contributions to neuropsychiatric disease. Here, we believe we provide for human NMDAR1-autoantibodies the first comprehensive analysis of their target epitopes and functionality. We selected sera of representative carriers, healthy or diagnosed with very diverse conditions, that is, schizophrenia, age-related disorders like hypertension and diabetes, or anti-NMDAR encephalitis. We show that all positive sera investigated, regardless of source (ill or healthy donor) and immunoglobulin class, provoked NMDAR1 internalization in human-induced pluripotent stem cell-derived neurons and reduction of glutamate-evoked currents in NR1-1b/NR2A-expressing Xenopus oocytes. They displayed frequently polyclonal/polyspecific epitope recognition in the extracellular or intracellular NMDAR1 domains and some additionally in NR2A. We conclude that all circulating NMDAR1-autoantibodies have pathogenic potential regarding the whole spectrum of neuronal NMDAR-mediated effects upon access to the brain in situations of increased blood-brain-barrier permeability.

Correlation between slaughter practices and the distribution of Salmonella and hygiene indicator bacteria on pig carcasses during slaughter.

This study investigated the distribution of hygiene indicator bacteria and Salmonella on pig carcasses. Moreover, the relation between hygiene indicator counts and Salmonella presence as well as associations between specific slaughter practices and carcass contamination were determined for each carcass area. Seven Belgian pig slaughterhouses were visited three times to swab five randomly selected carcasses at nine different areas, after evisceration and trimming. Information about slaughter practices was collected using a questionaire. In all samples, the E. coli and Salmonella presence was analyzed and Enterobacteriaceae and total aerobic bacteria were quantified. Average total aerobic counts ranged from 3.1 (loin, pelvic duct, ham) to 4.4 log10 CFU/cm2 (foreleg). Median Enterobacteriaceae numbers varied between 0.4 (ham) an 1.8 log10 CFU/cm2 (foreleg). E. coli and Salmonella presence ranged from 15% (elbow) to 89% (foreleg) and 5% (elbow) to 38% (foreleg), respectively. Positive relations were found between hygiene indicator counts and Salmonella presence at the head, sternum, loin and throat. Several slaughter practices, such as splitting the head and incising tonsils, were associated with higher levels of hygiene indicator bacteria and Salmonella. These findings can be used to educate slaughterhouse personnel and estimate the public health risk involved in consumption of different pork cuts.

EnsCat: clustering of categorical data via ensembling.

BACKGROUND: Clustering is a widely used collection of unsupervised learning techniques for identifying natural classes within a data set. It is often used in bioinformatics to infer population substructure. Genomic data are often categorical and high dimensional, e.g., long sequences of nucleotides. This makes inference challenging: The distance metric is often not well-defined on categorical data; running time for computations using high dimensional data can be considerable; and the Curse of Dimensionality often impedes the interpretation of the results. Up to the present, however, the literature and software addressing clustering for categorical data has not yet led to a standard approach. RESULTS: We present software for an ensemble method that performs well in comparison with other methods regardless of the dimensionality of the data. In an ensemble method a variety of instantiations of a statistical object are found and then combined into a consensus value. It has been known for decades that ensembling generally outperforms the components that comprise it in many settings. Here, we apply this ensembling principle to clustering. We begin by generating many hierarchical clusterings with different clustering sizes. When the dimension of the data is high, we also randomly select subspaces also of variable size, to generate clusterings. Then, we combine these clusterings into a single membership matrix and use this to obtain a new, ensembled dissimilarity matrix using Hamming distance. CONCLUSIONS: Ensemble clustering, as implemented in R and called EnsCat, gives more clearly separated clusters than other clustering techniques for categorical data. The latest version with manual and examples is available at https://github.com/jlp2duke/EnsCat .

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL).

BACKGROUND: Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed. PATIENTS AND METHODS: The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors. RESULTS: With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS. CONCLUSION: TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

Propionibacterium acnes populations involved in deep pathological samples and their dynamics along the cardiac surgical pathway.

Propionibacterium acnes belongs to the normal skin microbiota, but it is also responsible for acne vulgaris and causes serious infections such as endocarditis and surgical site infections (SSI). The P. acnes population is structured into phylogenetic groups, with phylotype I being associated with acne. Herein, we explore the link between phylotypes and clinical origins in a collection of P. acnes isolated from different body sites, involved in deep infections or healthcare-associated infections (HAI), with particular emphasis on strains from cardiac SSI. Cardiac SSI have been further studied in terms of P. acnes population dynamics during the care pathway. The recA and tly genes phylotypes were compared to hemolytic behavior, susceptibility to antimicrobial agents, and clinical origins. An original approach of recA polymerase chain reaction temporal temperature gel electrophoresis (PCR-TTGE) was developed and applied for the direct identification of P. acnes phylotypes in surgical samples, in order to assess their temporal dynamics during the surgical course. Our results underlined the preferential involvement of IA-2/IB and II phylogroups in HAI and SSI. Unlike IA and II, type IA-2/IB presented a gradual increase with the depth of sampling in the peroperative phase of cardiac surgery. Phylotypes IA and IA-2/IB were both predominant in scar tissues and on postoperative skin, suggesting a specific predisposition to recolonize skin. Particular association of the phylotype IA-2/IB with SSI and its propensity to colonize wounds in cardiac surgery was observed. We assumed that the follow-up of P. acnes phylotypes during pathological processes could give new clues for P. acnes pathogenicity.

Epidemic increase in Salmonella bloodstream infection in children, Bwamanda, the Democratic Republic of Congo.

Salmonella enterica is the leading cause of bloodstream infection in children in sub-Saharan Africa, but few data are available from Central-Africa. We documented during the period November 2011 to May 2012 an epidemic increase in invasive Salmonella bloodstream infections in HGR Bwamanda, a referral hospital in Equateur Province, DR Congo. Salmonella spp. represented 90.4 % (103 out of 114) of clinically significant blood culture isolates and comprised Salmonella Typhimurium (54.4 %, 56 out of 103), Salmonella Enteritidis (28.2 %, 29 out of 103) and Salmonella Typhi (17.5 %, 18 out of 103), with Salmonella Enteritidis accounting for most of the increase. Most (82 out of 103, 79.6 %) isolates were obtained from children < 5 years old. Median ages of patients infected with Salmonella Typhimurium and Salmonella Enteritidis were 14 months (14 days to 64 years) and 19 months (3 months to 8 years) respectively. Clinical presentation was non-specific; the in-hospital case fatality rate was 11.1 %. More than two thirds (69.7 %, 53 out of 76) of children < 5 years for whom laboratory data were available had Plasmodium falciparum infection. Most (83/85, 97.6 %) non-typhoid Salmonella isolates as well as 6/18 (33.3 %) Salmonella Typhi isolates were multidrug resistant (i.e. resistant to the first-line oral antibiotics amoxicillin, trimethoprim-sulfamethoxazole and chloramphenicol), one (1.0 %) Salmonella Typhimurium had decreased ciprofloxacin susceptibility owing to a point mutation in the gyrA gene (Gly81Cys). Multilocus variable-number tandem-repeat (MLVA) analysis of the Salmonella Enteritidis isolates revealed closely related patterns comprising three major and four minor profiles, with differences limited to one out of five loci. These data show an epidemic increase in clonally related multidrug-resistant Salmonella bloodstream infection in children in DR Congo.

Multidisciplinary investigation of a multicountry outbreak of Salmonella Stanley infections associated with turkey meat in the European Union, August 2011 to January 2013.

Between August 2011 and January 2013, an outbreak of Salmonella enterica serovar Stanley (S. Stanley) infections affected 10 European Union (EU) countries, with a total of 710 cases recorded. Following an urgent inquiry in the Epidemic Intelligence Information System for food- and waterborne diseases (EPIS-FWD) on 29 June 2012, an international investigation was initiated including EU and national agencies for public health, veterinary health and food safety. Two of three local outbreak investigations undertaken by affected countries in 2012 identified turkey meat as a vehicle of infection. Furthermore, routine EU monitoring of animal sources showed that over 95% (n=298) of the 311 S. Stanley isolates reported from animal sampling in 2011 originated from the turkey food production chain. In 2004­10, none had this origin. Pulsed-field gel electrophoresis (PFGE) profile analysis of outbreak isolates and historical S. Stanley human isolates revealed that the outbreak isolates had a novel PFGE profile that emerged in Europe in 2011. An indistinguishable PFGE profile was identified in 346 of 464 human, food, feed, environmental and animal isolates from 16 EU countries: 102 of 112 non-human isolates tested were from the turkey production chain. On the basis of epidemiological and microbiological evidence, turkey meat was considered the primary source of human infection, following contamination early in the animal production chain.

Residual risk of Pseudomonas aeruginosa waterborne contamination in an intensive care unit despite the presence of filters at all water points-of-use.

OBJECTIVE: To assess the residual risk of waterborne contamination by Pseudomonas aeruginosa from a water network colonized by a single genotype [sequence type (ST) 299] despite the presence of antimicrobial filters in a medical intensive care unit (ICU). METHODS: During the first 19-month period since the ICU opened, contamination of the water network was assessed monthly by collecting water upstream of the filters. Downstream water was also sampled to assess the efficiency of the filters. P. aeruginosa isolates from patients were collected and compared with the waterborne ST299 P. aeruginosa by multiplex-rep polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. Cross-transmission events by other genotypes of P. aeruginosa were also assessed. RESULTS: Overall, 1.3% of 449 samples of filtered water were positive for P. aeruginosa in inoculum, varying between 1 and 104 colony-forming units/100 mL according to the tap. All P. aeruginosa hydric isolates belonged to ST299 and displayed fewer than two single nucleotide polymorphisms (SNPs). Among 278 clinical isolates from 122 patients, 10 isolates in five patients showed identical profiles to the hydric ST299 clone on both multiplex-rep PCR and PFGE, and differed by an average of fewer than five SNPs, confirming the water network reservoir as the source of contamination by P. aeruginosa for 4.09% of patients. Cross-transmission events by other genotypes of P. aeruginosa were responsible for the contamination of 1.75% of patients. DISCUSSION/CONCLUSION: Antimicrobial filters are not sufficient to protect patients from waterborne pathogens when the water network is highly contaminated. A microbiological survey of filtered water may be needed in units hosting patients at risk of P. aeruginosa infections, even when all water points-of-use are fitted with filters.

Healthcare worker protection against mpox contamination: position paper of the French Society for Hospital Hygiene.

In the context of the recent re-emergence of mpox worldwide, the French Society for Hospital Hygiene (SF2H) performed a literature review of the transmission paths and proposed specific recommendations for healthcare workers (HCWs) caring for patients with suspected or confirmed MPXV. In developed countries, the risk of contamination among HCWs in healthcare facilities seemed to be very low, limited to contamination through needle stick injuries. Two additional contamination cases were reported and not fully explained. Beyond healthcare settings, the analysis of the literature highlighted (i) a main contamination route during sexual intercourse, mainly among men who have sex with men, and (ii) a very low secondary attack rate in other contexts, such as schools or jails. Numerous studies have reported molecular or virus identification on surfaces or in the air surrounding patients, without any association with the low secondary case incidence; moreover, the minimum infectious dose through air or mucosal exposure is still unknown. Owing to the lack of evidence of MPXV respiratory transmission in the healthcare setting, the SF2H recommends the implementation of standard and contact precautions combined with medical/surgical mask use. Owing to the lack of evidence of transcutaneous contamination, the SF2H recommends the use of gloves only if contact with cutaneous lesions or mucous membranes occurs. Regarding the risk of contamination from the environment in healthcare facilities, additional studies must be conducted to investigate this.

Transmission of multiple resistant Salmonella Concord from internationally adopted children to their adoptive families and social environment: proposition of guidelines.

Since 2004, an increasing number of multidrug-resistant Salmonella serovar Concord infections have been isolated in Belgium among children adopted from Ethiopia. The patients or their family were interviewed and the isolates were subtyped. Between 2004 and 2009, a total of 39 Salmonella Concord infections were isolated from patients. Thirty-four isolates presented a multidrug resistance including resistance to extended-spectrum cephalosporins. Thirty-six cases involved children and 30 of these were adopted from Ethiopia. One case was due to contact with an adopted child and for the other 5 cases no direct epidemiological link with Ethiopia could be found, although four isolates displayed the same patterns observed on the adoptees' isolates, strongly suggesting a phylogenetic relationship with the Ethiopian isolates. Our study confirmed the emergence in Europe of S. Concord isolates resistant to third-generation cephalosporin among Ethiopian adoptees. We have demonstrated that transmission (intra- and extra familial) can happen even if the frequency seems to be low. The presence and the transmission of such a multidrug-resistant Salmonella infection constitute a major concern, since such strains could jeopardize classical antibiotic therapy in patients at risk. This study provides useful information for parents adopting children and for their family practitioner.

Usefulness of the European Epidemic Intelligence Information System in the management of an outbreak of listeriosis, Belgium, 2011.

A cluster of time-linked cases and the identification of a clonal strain suggest the occurrence of an outbreak of listeriosis in Belgium in 2011, presumably due to the consumption of hard cheese made with pasteurised milk and produced by a Belgium manufacturer. The outbreak clone was identified as Listeria monocytogenes serovar 1/2a, sensitive to arsenic and cadmium and of multilocus sequence typing MLST-type 37. Food investigation of this outbreak was facilitated by the European Epidemic Intelligence Information System and data exchanged between French and Belgium listeriosis surveillance systems.

Investigation of an excess of Salmonella enteritidis phage type 14b and MLVA type 4-7-3-13-10-2-2 in Luxembourg, Belgium and Germany during 2010.

We investigated an increase of human cases of Salmonella Enteritidis occurring from August until November 2010 in Belgium, Luxembourg and Germany involving an estimated three hundred laboratory confirmed cases. Molecular typing indicated that the increase in Luxembourg and Belgium was due a particular strain having phage type 14b, MLVA pattern 4-7-3-13-10-2-2 and fully susceptible to the Enternet panel of antibiotics. MLVA and phage typing were found to have similar discriminatory power on a collection of 40 Belgian and Luxembourg strains isolated during 2010. Epidemiological investigations in Luxembourg suggested eggs as a possible source for some cases, although supermarket eggs tested were negative. No other EU countries observed a substantial increase of cases, although three smaller outbreaks in Germany were also due to a strain with the same phage type and MLVA pattern. In 2010 the EU directive banning battery cages came into force in Germany followed by a dioxin food scare incident. Given that the EU Laying Hens Directive will come into force across all Member States in 2012, a closer monitoring of Salmonella contamination of imported eggs at retail and wholesale level is recommended.

Stratification of the channel domain in neurotransmitter receptors.

Analyses of the ionic pore of ligand-gated ion channels at the amino acid level reveal a structural and functional stratification of the M2 channel domain. Mutations in the equatorial and outer regions affect channel gating, whereas mutations of other amino acid rings alter ionic permeability or selectivity.

Shigellosis outbreak linked to canteen-food consumption in a public institution: a matched case-control study.

On 13 November 2009, the authorities of Flemish Brabant, Belgium, received an alert concerning a potential outbreak of Shigella sonnei at a public institution. A study was conducted to assess the extent, discover the source and to implement further measures. We performed a matched case-control study to test an association between shigellosis and canteen-food consumption. Water samples and food handlers' faecal samples were tested. The reference laboratory characterized the retrospectively collected Shigella specimens. We found 52 cases distributed over space (25/35 departments) and time (2 months). We found a matched odds ratio of 3·84 (95% confidence interval 1·02-14·44) for canteen-food consumption. A food handler had travelled to Morocco shortly before detection of the first laboratory-confirmed case. Water samples and food handlers' faecal samples tested negative for Shigella. Confirmed cases presented PFGE profiles, highly similar to archived isolates from Morocco. Foodborne transmission associated with the canteen was strongly suspected.

Outbreak of Shigella sonnei infections in the Orthodox Jewish community of Antwerp, Belgium, April to August 2008.

In the beginning of April 2008 three cases of Shigella sonnei infection were identified among the Orthodox Jewish community of Antwerp, Belgium. We conducted a descriptive study and a household cohort study to identify potential risk factors. Stool samples were cultured and antibiotic susceptibility of the isolates was determined. Between April and August 2008, 42 cases were registered. All characterised isolates (n=20) shared an identical pulsed-field gel electrophoresis profile and were indistinguishable from one of the twelve main strains detected in Israel in 2008, where the index case's father had stayed before the outbreak. The secondary attack rate in households was 8.5% (95% confidence interval (CI): 4.3­12.7). Multivariate analysis identified the following risk factors for secondary spread: households with more than three children (adjusted relative risk (RR): 9.17; 95% CI: 1.21­69.13), children younger than five years (adjusted RR: 5.45; 95% CI: 2.44­12.62), and children younger than 12 years assisting in washing younger siblings (adjusted RR: 5.45; 95% CI: 2.44­12.17). Rigorous hand washing, use of disposable towels, information for parents and caregivers, and exclusion of symptomatic children from day care, preschool and school for a minimum of 48 hours were implemented.

Microbiological and molecular investigation of an increase of human listeriosis in Belgium, 2006-2007.

In Belgium, the majority of cases of listeriosis are sporadic cases. In this study we present evidence for an episode of listeriosis: a time-linked cluster of cases that occurred in 2006 and 2007, and the identification of identical strains. The episode involved 11 patients, infected with Listeria monocytogenes of serovar 4b. The source of infection was not detected.