Psychological and Psychophysiological Effects of a High-Mountain Expedition to Tibet

In March 1999 a team of 8 mountaineers (6 men and 2 women) climbed up the 6th highest mountain of the world: The Cho Oyo (8201 m), located in the high mountains of Tibet. During the expedition, we investigated the effects of high mountaineering on various psychological variables (e.g., anxiety) and psychophysiological variables (e.g. blood pressure, pulse, skin-resistance) as well as the ability to relax at different points of time (2 premeasures before, three measures during, and one post-measure immediate after the Expedition). Due to a long-term monitoring of the skin resistance, we can summarize that three different adaptation levels can be defined, that appear under increasing pressure: Inhibition of overload, unspecific hypersensibility and exhaustion. The results can show that a telemedical assessment is possible and necessary even under the circumstances of a highmountaineering expedition in order to determine and predict deficits in behaviour and health risks for individuals at high altitudes

Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals.

HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 and their ligand PVR are altered in viral infections and cancer. However, the extent to which the TIGIT/CD226/PVR-axis is affected by HIV-infection has not been characterized. Here, we report that TIGIT expression increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T cells, despite early ART. These findings highlight the importance of the TIGIT/CD226/PVR axis as an immune checkpoint barrier that could hinder future "cure" strategies requiring potent HIV-specific CD8+ T cells

Transport Properties of Multiple Quantum Dots Arranged in Parallel: Results from the Bethe Ansatz

In this paper we analyze transport through a double dot system connected to two external leads. Imagining each dot possessing a single active level, we model the system through a generalization of the Anderson model. We argue that this model is exactly solvable when certain constraints are placed upon the dot Coulomb charging energy, the dot-lead hybridization, and the value of the applied gate voltage. Using this exact solvability, we access the zero temperature linear response conductance both in and out of the presence of a Zeeman field. We are also able to study the finite temperature linear response conductance. We focus on universal behaviour and identify three primary features in the transport of the dots: i) a so-called RKKY Kondo effect; ii) a standard Kondo effect; and iii) interference phenomena leading to sharp variations in the conductance including conductance zeros. We are able to use the exact solvability of the dot model to characterize these phenomena quantitatively. While here we primarily consider a double dot system, the approach adopted applies equally well to N-dot systems.Comment: 28 pages, 10 figures; references added in v

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies

Drawing-writing culture: the truth-fiction spectrum of an ethno-graphic novel on the Sri Lankan civil war and migration

With our focus on an “ethno‐graphic novel” on the Sri Lankan civil war and the forcible displacement and migration of Tamil survivors, we make two main propositions while reflecting on the “graphic narrative turn” that has emerged in anthropology in recent years. First, we inscribe drawing into the “writing of cultures” where words have held a superior status in ethnographic representations. Rather than seeing drawings as perceptive tools for recording scenes in fieldwork alone, we extend them to a representational practice where they can have a deep, intricate, and equivalent entanglement with words to create synchronous affective intensities among a larger audience. Our second proposal follows Jean Rouch on cinéma vérité to interrogate assumptions about truth and fiction as portrayed by film representations. We propose a theory and practice for graphic novel production that we have termed vérités graphiques (literally, graphic realities). This describes the collaborative and interactive engagement with people's contributions and views, and their distillation and fictionalization through the ethno‐graphic form. We diverge from cinéma vérité, however, by highlighting a truth‐fiction spectrum that further challenges the presumed objectivity of what is seen, experienced, co‐created, and revealed

Diagnostic reliability of the Berlin classification for complex MCA aneurysms—usability in a series of only giant aneurysms

Background and objective The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set. Methods We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers. Results We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419. Conclusion The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.Peer reviewe

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4⁺ T cell depletion.

We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8(+) T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francisco, were monitored from an estimated 44 days postinfection for up to 6 years. CD8(+) T cells responses targeting HLA-matched HIV-Gag-epitopes were identified and characterized by multicolor flow cytometry. The autologous HIV gag sequences were obtained. We demonstrate that patients targeting a conserved HIV-Gag-epitope in early infection maintained their epitope-specific CD8(+) T cell response throughout the study period. Patients targeting a variable epitope showed decreased immune responses over time, although there was no limitation of the functional profile, and they were likely to target additional variable epitopes. Maintained immune responses to conserved epitopes were associated with no or limited sequence evolution within the targeted epitope. Patients with immune responses targeting conserved epitopes had a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log(10) difference). Furthermore, the rate of CD4(+) T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a variable epitope (1.85% per month). Previous studies have shown that targeting of antigens based on specific HLA types is associated with a better disease course. In this study we show that categorizing epitopes based on their variability is associated with clinical outcome