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MIRAGE syndrome is a multisystem disorder caused by mutations in SAMD9 (sterile α motif domain-containing protein 9) with a high mortality in the first decade of life. We generated 2 human induced pluripotent stem cell lines from male children diagnosed with MIRAGE syndrome. The cell lines were generated from fibroblasts by integration-free reprogramming using the Sendai virus. Both cell lines were fully characterized regarding their pluripotent identity and differentiation potential, and quality controlled for karyotypic integrity, cell line identity and clearance of reprogramming vectors. The generated cell lines represent a valuable tool to study the disease mechanism of MIRAGE syndrome.

An intervention for Gram-negative bloodstream infections that integrated mass spectrometry technology for rapid diagnosis with antimicrobial stewardship oversight significantly improved patient outcomes and reduced hospital costs. As antibiotic resistance rates continue to grow at an alarming speed, the current study was undertaken to assess the impact of this intervention in a challenging patient population with bloodstream infections caused by antibiotic-resistant Gram-negative bacteria.A total of 153 patients with antibiotic-resistant Gram-negative bacteremia hospitalized prior to the study intervention were compared to 112 patients treated post-implementation. Outcomes assessed included time to optimal antibiotic therapy, time to active treatment when inactive, hospital and intensive care unit length of stay, all-cause 30-day mortality, and total hospital expenditures.Integrating rapid diagnostics with antimicrobial stewardship improved time to optimal antibiotic therapy (80.9 h in the pre-intervention period versus 23.2 h in the intervention period, P0.001) and effective antibiotic therapy (89.7 h versus 32 h, P0.001). Patients in the pre-intervention period had increased duration of hospitalization compared to those in the intervention period (23.3 days versus 15.3 days, P = 0.0001) and longer intensive care unit length of stay (16 days versus 10.7 days, P = 0.008). Mortality among patients during the intervention period was lower (21% versus 8.9%, P = 0.01) and our study intervention remained a significant predictor of survival (OR, 0.3; 95% confidence interval [CI], 0.12-0.79) after multivariate logistic regression. Mean hospital costs for each inpatient survivor were reduced $26,298 in the intervention cohort resulting in an estimated annual cost savings of $2.4 million (P = 0.002).Integration of rapid identification and susceptibility techniques with antimicrobial stewardship resulted in significant improvements in clinical and financial outcomes for patients with bloodstream infections caused by antibiotic-resistant Gram-negatives. The intervention decreased hospital and intensive care unit length of stay, total hospital costs, and reduced all-cause 30-day mortality.

Introduction Microbiology culture is the "gold standard" for diagnosis of fungal infections; however, culture has a lengthy turnaround time. A more timely assessment is possible with cytology and Gomori-methamine silver (GMS) staining. Materials and methods A total of 100 respiratory tract specimens with a positive fungal Gomori-methamine silver stain and corresponding culture were selected. The cytology slides were reviewed for factors contributing to discrepant results. Specimens were classified as 2 types of variances: interpretative and sampling. Concordant diagnoses were also evaluated. Results Eighty-two cases had fungal organisms that grew in culture. The remaining 18 cases were composed solely of fungal organisms that did not grow in culture (17 cases with Pneumocystis jirovecii ; 1 case with Pityrosporum ovale ). These 18 cases were excluded from the variance analysis. Thirty-three of 82 cases (40%) had concordant cytology and microbiology results, whereas 49 cases were discrepant. Variances were both sampling (41 cases) and interpretive (8 cases). Interpretive variances were predominantly Aspergillus species misinterpreted as Candida . Difficulty identifying true septate hyphae was the major contributing factor for misinterpretation. Conclusions Cytologic evaluation of respiratory specimens remains a useful preemptive diagnostic tool in the rapid diagnosis of fungal infection. Cytology samples significantly contribute to the diagnosis of respiratory fungi. However, interpretive variances between Aspergillus and Candida organisms are common. Awareness of the characteristic features that distinguish fungal organisms can further improve the diagnostic utility of cytology.

The development of a direct competitive enzyme-linked immunosorbent assay (ELISA) based on polyclonal antibodies specific for semicarbazide (SEM) is described. Molecular modelling of the hapten mimics and other key components of the assay system was conducted to explain antibody properties in relation to hapten design. The small aliphatic molecule SEM was coupled to 3-carboxybenzaldehyde to produce carboxyphenyl-SEM (CPSEM), for the generation of specific antibodies. Five rabbits produced antibodies against NPSEM (used in direct and indirect ELISA formats) exhibiting a 50% binding inhibition level (IC(50) values) of 0.06-2.28 microgL(-1) in assay buffer for SEM. The most sensitive indirect assay based on the antibody MVK39 showed a high dynamic range providing a linear readout in the range of 0.01-0.2 microgL(-1). Antibody MVK31 (IgG) allowed specific SEM detection at an IC(50)=0.14 microgL(-1) in direct ELISA and was evaluated using solvent extracted SEM-spiked porcine and baby food samples. Recovery levels determined from fortified samples (0.5, 1.0, 1.5, 5, 10 and 20 microgkg(-1)) of porcine and baby food ranged from 82.9 to 105.3%, respectively, with a coefficient of variation less than 15.5%. Respective detection capability and threshold of the assay for porcine muscle, set on the basis of acceptance of no false negative results, was 0.3 and 0.11 microgkg(-1).

Validation of the MycoAlign assay, a newly developed Mycobacterium spp. identification system based on internal transcribed spacer-1 sequencing, was performed using 50 acid-fast bacilli (AFB)-positive clinical laboratory specimens. Forty-three (86%) diagnostic-level results were obtained, including 38 Mycobacterium spp. and 5 other AFB-positive genera. Three isolates (6%) had suboptimal identity scores with high probability (81-87% identity score). Four (8%) mixed-pattern results were obtained. Forty-five (90%) observations were concordant with the species identification by standard methods, including all controls.

The Atlas muon spectrometer relies on Monitored Drift Tubes (MDTs) for track reconstruction in most regions. Expected count rates due to background photons reach up to 1500 Hz/cm for the innermost MDTs. For a gas gain of 2 ⋅ 10 4 this rate corresponds to an overall accumulated charge of up to 0.6 C/cm in 10 years of LHC operation. The focus of the present ageing studies is on testing complete modules from the ongoing chamber production chain in realistic Atlas conditions. This paper summarizes the results of such a study performed at the CERN Gamma Irradiation Facility GIF. One of the main goals was to evaluate for the first time the principle of gas recirculation with a prototype of the Atlas circulation system.

Fungi are important etiologic agents of sinusitis. However, features of fungal sinusitis including the histologic spectrum, diagnostic mishaps, incidence, and fungal types have not been systematically studied. From 1996 through 2001, a total of 788 surgical pathology sinus specimens from 384 cases was retrieved. Fungal sinusitis was diagnosed in 58 specimens (7%) from 47 cases (12%). Four histologic categories of fungal sinusitis were identified: (1) allergic fungal sinusitis in 34 cases (copious mucin, abundant eosinophils, Charcot-Leyden crystals (so-called allergic mucin), with rare noninvasive fungal hyphae); (2) mycetoma/fungus ball in 11 cases (tightly packed fungal hyphae without allergic mucin or tissue invasion); (3) chronic invasive fungal sinusitis in 1 case (tissue granulomas with fungal hyphae); and (4) acute fulminant fungal sinusitis in 1 case (fungal vascular invasion). The diagnosis was initially missed in 16/34 (47%) cases of allergic fungal sinusitis despite typical features; incorrect classification was noted in 47% of cases. Sixty-seven percent of cases had positive fungal cultures, dematiaceous fungi being the most common. Allergic fungal sinusitis accounted for the majority of fungal sinusitis. Although misdiagnosis or incorrect classification is rather frequent for fungal sinusitis, awareness of the distinctive morphologic features of this entity may prevent these errors.

The basis of olfactory signatures mediating human kin recognition was investigated in two experiments. The odors of mothers and offspring were correctly matched (by subjects unfamiliar with the stimulus individuals) at a greater than chance frequency. In contrast, subjects were not able reliably to match the odors of husbands and wives. These data support the hypotheses that characteristic individuals odors are genetically mediated and that kin recognition should be facilitated by the similarity of such familiar odors among close relatives.

Social interactions among unfamiliar Acomys cahirinus pups are observed following removal from the home cage and parents. Huddling by 14- to 22-day-old pups declines sharply as the age of the pups increases. This reduced responsiveness to unfamiliar agemates coincides with a downward trend in suckling rate from Days 16 through 22, indicating that with the approach of final weaning animals become more discriminating in choice of social partners. Compared to singly reared pups, those reared with 2 to 3 littermates subsequently display more frequent huddling with unfamiliar agemates and are more successful in a food competition test. Experience with littermates appears to result in increased social competence after weaning.

The epidemiology of genital white piedra was investigated in 166 young men with a variety of genital complaints. Trichosporon beigelii was isolated from sixty-six (40%) of the cultured scrotal hairs. Infection was more common among black patients--54% of those examined, compared to 16% of white patients and 30% of "others" (p less than 0.001). There was no relationship between infection and foreign travel. White piedra was also found in young women, but less frequently than in young men (14% vs 40%, respectively). Transmission rarely occurred from person to person. Occasionally multiple body sites were simultaneously infected. A relationship may exist between T. beigelii and Corynebacterium concurrently infecting genital hair shafts. Eradication of infection was extremely difficult, despite in vitro sensitivity to antifungal agents. Spontaneous remissions occurred, however, in some patients.