Dipole-dipole correlations and the Debye process in the dielectric response of non-associating glass forming liquids

The non-exponential shape of the $\alpha$-process observed in supercooled liquids is considered as one of the hallmarks of glassy dynamics and has thus been under study for decades, but is still poorly understood. For a polar van der Waals liquid, we show here - in line with a recent theory - that dipole-dipole correlations give rise to an additional process in the dielectric spectrum slightly slower than the $\alpha$-relaxation, which renders the resulting combined peak narrower than observed by other experimental techniques. This is reminiscent of the Debye process found in monohydroxy alcohols. The additional peak can be suppressed by weakening the dipole-dipole interaction via dilution with a nonpolar solvent

Impairment in predictive processes during auditory mismatch negativity in ScZ: evidence from event-related fields

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities

Universal Structural Relaxation in Supercooled Liquids

One of the hallmarks of molecular dynamics in deeply supercooled liquids is the non-exponential character of the relaxation functions. It has been a long standing issue if 'universal' features govern the lineshape of glassy dynamics independent of any particular molecular structure or interaction. In the paper, we elucidate this matter by giving a comprehensive comparison of the spectral shape of depolarized light scattering and dielectric data of deeply supercooled liquids. The light scattering spectra of very different systems, e.g. hydrogen bonding and van der Waals liquids but also ionic systems, almost perfectly superimpose and show a generic lineshape of the structural relaxation, approximately following a high frequency power law $\omega^{-1/2}$ . However, the dielectric loss peak shows a more individual shape. In systems with low dipole moment generic behavior is also observed in the dielectric spectra, while in strongly dipolar liquids additional crosscorrelation contributions mask the generic structural relaxation

Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (⁠R1⁠), effective transverse relaxation rate (⁠R2∗⁠), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (⁠R2∗ at 3T, R1 at 7T), endothelial cells (⁠R1 and MTsat at 3T), microglia (⁠R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes and oligodendrocyte precursor cells (⁠R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types

Efficacy of omalizumab in mastocytosis: allusive indication obtained from a prospective, double-blind, multicenter study (XOLMA Study)

BACKGROUND: Patients with mastocytosis often suffer from a variety of symptoms caused by mast cell mediators where treatments remain difficult, showing various success rates. Omalizumab, a monoclonal anti-IgE antibody, has been postulated to have a positive impact on mastocytosis-associated symptoms such as flush, vertigo, gastrointestinal problems, or anaphylaxis. OBJECTIVE: To investigate the efficacy and safety of omalizumab in systemic mastocytosis. METHODS: Patients with histologically proven mastocytosis were investigated in a multicenter prospective double-blind placebo-controlled trial to receive either omalizumab or placebo, dosed according to IgE and body weight. The primary endpoint was change in the AFIRMM activity score after 6 months of treatment. Different laboratory parameters were analyzed. RESULTS: Sixteen patients were analyzed: 7 to omalizumab and 9 to placebo (mean age 47.7 ± 13.8 vs. 45.4 ± 8.8 years; 66.6 vs. 85.7% were female; mean disease duration 10.0 ± 5.1 vs. 4.5 ± 2.9 years, respectively). After 6 months the median AFIRMM score decreased 50% from 52.0 to 26.0 in the omalizumab group versus 104.0-102.0 in the placebo group (p = 0.286); however, the difference was not significant (p = 0.941). Secondary endpoints, including the number of allergic reactions, changes in major complaints, wheal-and-flare reaction due to mechanical irritation (Darier's sign), and frequency of the use of mastocytosis-specific drugs improved in the omalizumab group, but not significantly. Adverse events like urticaria, bronchospasm, and anaphylactic shock showed no significant difference between the groups. No severe adverse events occurred. FcεRI (Fc-epsilon receptor) expression on basophils decreased after receiving omalizumab versus placebo. CONCLUSION: Omalizumab was safe and showed a tendency to improve mastocytosis-related symptoms, in particular diarrhea, dizziness, flush, and anaphylactic reactions, including the AFIRMM score and secondary endpoints; however, the difference was not significant. Due to the small study size and difference at baseline between the study groups, further studies are required to confirm our findings

Tracking a Tuberculosis Outbreak Over 21 Years: Strain-Specific Single-Nucleotide Polymorphism Typing Combined With Targeted Whole-Genome Sequencing

Background. Whole-genome sequencing (WGS) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. We combined strain-specific single-nucleotide polymorphism (SNP) typing and targeted WGS to investigate a tuberculosis cluster spanning 21 years in Bern, Switzerland. Methods. On the basis of genome sequences of 3 historical outbreak Mycobacterium tuberculosis isolates, we developed a strain-specific SNP-typing assay to identify further cases. We screened 1642 patient isolates and performed WGS on all identified cluster isolates. We extracted SNPs to construct genomic networks. Clinical and social data were retrospectively collected. Results. We identified 68 patients associated with the outbreak strain. Most received a tuberculosis diagnosis in 1991-1995, but cases were observed until 2011. Two thirds were homeless and/or substance abusers. Targeted WGS revealed 133 variable SNP positions among outbreak isolates. Genomic network analyses suggested a single origin of the outbreak, with subsequent division into 3 subclusters. Isolates from patients with confirmed epidemiological links differed by 0-11 SNPs. Conclusions. Strain-specific SNP genotyping allowed rapid and inexpensive identification of M. tuberculosis outbreak isolates in a population-based strain collection. Subsequent targeted WGS provided detailed insights into transmission dynamics. This combined approach could be applied to track bacterial pathogens in real time and at high resolutio

Tuberculosis in HIV-Negative and HIV-Infected Patients in a Low-Incidence Country: Clinical Characteristics and Treatment Outcomes

BACKGROUND: In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000-2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P<0.0001) and to present disseminated disease (23.9% vs. 3.4%, P<0.0001) than HIV-negative patients. Coinfected patients not enrolled in the SHCS were asylum seekers or migrant workers, with lower CD4 cell counts at TB diagnosis (median CD4 count 79 cells/µL compared to 149 cells/µL among SHCS patients, P = 0.07). There were 6 patients (60.0%) with successful outcomes compared to 82 (88.2%) patients in the SHCS (P = 0.023). CONCLUSIONS: The clinical presentation of coinfected patients differed from HIV-negative TB patients. The number of HIV-infected patients diagnosed with TB outside the SHCS is similar to the number diagnosed within the cohort but outcomes are poorer in patients not followed up in the national cohort. Special efforts are required to address the needs of this vulnerable population

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration