Efavirenz-induced urolithiasis

We describe the first case of efavirenz-induced urolithiasis in a 47-year-old HIV-positive patient. Urinary obstruction led to pyelonephritis and septic shock, requiring emergency ureteral catheterisation. The subsequent clinical course was favourable, allowing the patient's discharge on day5. A 7mm, radio-translucent, non-crystalline, beige stone was extracted during catheterisation. Stone analysis by Fourier transform infrared spectrometry, liquid chromatography and mass spectrometry revealed a stone composed of efavirenz (EFV) metabolites M4, M5, M8 (as described by Mutlib et al. in 1999) and approximately 50% of unspecified proteins. EFV is a non-nucleoside reverse transcriptase inhibitor introduced to European markets in 1999. It is principally metabolised by cytochrome P450 3A4 and 2B6. Of the dose, 14-34% is excreted in the urine, 1% as unchanged drug. The patient had been taking 600mg EFV per day for 3years. As EFV-induced urolithiasis has not been reported so far, we would like to draw the attention of the medical community to this potentially severe complicatio

Derivation of the Rules of Quantum Mechanics from Information-Theoretic Axioms

Conventional quantum mechanics with a complex Hilbert space and the Born Rule is derived from five axioms describing properties of probability distributions for the outcome of measurements. Axioms I,II,III are common to quantum mechanics and hidden variable theories. Axiom IV recognizes a phenomenon, first noted by Turing and von Neumann, in which the increase in entropy resulting from a measurement is reduced by a suitable intermediate measurement. This is shown to be impossible for local hidden variable theories. Axiom IV, together with the first three, almost suffice to deduce the conventional rules but allow some exotic, alternatives such as real or quaternionic quantum mechanics. Axiom V recognizes a property of the distribution of outcomes of random measurements on qubits which holds only in the complex Hilbert space model. It is then shown that the five axioms also imply the conventional rules for all dimensions.Comment: 20 pages, 6 figure

Inland valley rice production systems and malaria infection and disease in the forest region of western Côte d'Ivoire

Background: This study aimed to determine the epidemiological impact of rice cultivation in inland valleys on malaria in the forest region of western Côte d'Ivoire. The importance of malaria was compared in terms of prevalence and parasite density of infections and also in terms of clinical malaria incidence between three agro-ecosystems: (i) uncultivated inland valleys, (R0), (ii) inland valleys with one annual rice cultivation in the rainy season, (R1) and (iii) developed inland valleys with two annual rice cultivation cycles, (R2). Methods: Between May 1998 and March 1999, seven villages of each agro-ecosystem (R0, R1 and R2) were randomly selected among villages pooled by farming system. In these 21 villages, a total of 1,900 people of all age groups were randomly selected and clinically monitored during one year. Clinical and parasitological information was obtained by active case detection of malaria episodes carried out during eight periods of five consecutive days scheduled at six weekly intervals and by cross-sectional surveys. Results: Plasmodium falciparum was the principal parasite observed in the three agro-ecosystems. A level of holoendemicity of malaria was observed in the three agro-ecosystems with more than 75% of children less than 12 months old infected. Geometric mean parasite density in asymptomatic persons varied between 180 and 206 P. falciparum asexual forms per μL of blood and was associated with season and with age, but not with farming system. The mean annual malaria incidence rate reached 0.7 (95% IC 0.5-0.9) malaria episodes per person in R0, 0.7 (95% IC 0.6-0.9) in R1 and 0.6 (95% IC 0.5-0.7) in R2. The burden of malaria was the highest among children under two years of age, with at least four attacks by person-year. Then malaria incidence decreased by half in the two to four-year age group. From the age of five years, the incidence was lower than one attack by person-year. Malaria incidence varied with season with more cases in the rainy season than in the dry season but not with farming system. Conclusion: In the forest area of western Côte d'Ivoire, inland valley rice cultivation was not significantly associated with malaria burden

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Aims/hypothesis: We evaluated the association of QT interval corrected for heart rate (QTc) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. Methods: We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 ± 0.6years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. Results: In subjects with type 1 diabetes QTc, but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10ms increase in QTc, 95% CI 1.02-1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02-1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03-1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QTc was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15-1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18-1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19-1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21-1.90, p < 0.001). Effect modification of QTc by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). Conclusions/interpretation: QTc is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabete

Charge separation and carrier dynamics in donor-acceptor heterojunction photovoltaic systems

Electron transfer and subsequent charge separation across donor-acceptor heterojunctions remain the most important areas of study in the field of third- generation photovoltaics. In this context, it is particularly important to unravel the dynamics of individual ultrafast processes (such as photoinduced electron transfer, carrier trapping and association, and energy transfer and relaxation), which prevail in materials and at their interfaces. In the frame of the National Center of Competence in Research “Molecular Ultrafast Science and Technology,” a research instrument of the Swiss National Science Foundation, several groups active in the field of ultrafast science in Switzerland have applied a number of complementary experimental techniques and computational simulation tools to scrutinize these critical photophysical phenomena. Structural, electronic, and transport properties of the materials and the detailed mechanisms of photoinduced charge separation in dye- sensitized solar cells, conjugated polymer- and small molecule-based organic photovoltaics, and high-efficiency lead halide perovskite solar energy converters have been scrutinized. Results yielded more than thirty research articles, an overview of which is provided here

Identification of Orch3, a Locus Controlling Dominant Resistance to Autoimmune Orchitis, as Kinesin Family Member 1C

Experimental autoimmune orchitis (EAO), the principal model of non-infectious testicular inflammatory disease, can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants. As previously established, the genome of DBA/2J mice encodes genes that are capable of conferring dominant resistance to EAO, while the genome of BALB/cByJ mice does not and they are therefore susceptible to EAO. In a genome scan, we previously identified Orch3 as the major quantitative trait locus controlling dominant resistance to EAO and mapped it to chromosome 11. Here, by utilizing a forward genetic approach, we identified kinesin family member 1C (Kif1c) as a positional candidate for Orch3 and, using a transgenic approach, demonstrated that Kif1c is Orch3. Mechanistically, we showed that the resistant Kif1c$^{D2}$ allele leads to a reduced antigen-specific T cell proliferative response as a consequence of decreased MHC class II expression by antigen presenting cells, and that the L$^{578}$→P$^{578}$ and S$^{1027}$→P$^{1027}$ polymorphisms distinguishing the BALB/cByJ and DBA/2J alleles, respectively, can play a role in transcriptional regulation. These findings may provide mechanistic insight into how polymorphism in other kinesins such as KIF21B and KIF5A influence susceptibility and resistance to human autoimmune diseases

Why do dogs (Canis familiaris) select the empty container in an observational learning task?

Many argue that dogs show unique susceptibility to human communicative signals that make them suitable for being engaged in complex co-operation with humans. It has also been revealed that socially provided information is particularly effective in influencing the behaviour of dogs even when the human’s action demonstration conveys inefficient or mistaken solution of task. It is unclear, however, how the communicative nature of the demonstration context and the presence of the human demonstrator affect the dogs’ object-choice behaviour in observational learning situations. In order to unfold the effects of these factors, 76 adult pet dogs could observe a communicative or a non-communicative demonstration in which the human retrieved a tennis ball from under an opaque container while manipulating another distant and obviously empty (transparent) one. Subjects were then allowed to choose either in the presence of the demonstrator or after she left the room. Results showed a significant main effect of the demonstration context (presence or absence of the human’s communicative signals), and we also found some evidence for the response-modifying effect of the presence of the human demonstrator during the dogs’ choice. That is, dogs predominantly chose the baited container, but if the demonstration context was communicative and the human was present during the dogs’ choice, subjects’ tendency to select the baited container has been reduced. In agreement with the studies showing sensitivity to human’s communicative signals in dogs, these findings point to a special form of social influence in observational learning situations when it comes to learning about causally opaque and less efficient (compared to what comes natural to the dog) action demonstrations

Nanoparticle Release from Thermal Decomposition of Polymer Nanocomposites and the Biological Potential of the Emissions

Adding nanoparticles to polymers improves the properties significantly, such as UV resistance or even electrical conductivity. The growing use of these composite materials leads to a higher amount in disposals eventually. Within the circular economy there are two ways of handling: the recycling by shredding and reuse and the thermal treatment by combustion in municipal waste incinerators. In both cases there is nearly no information about the behavior of the nanoparticles and possible release scenarios. In this study a laboratory burner is used as a flexible set up to incinerate the polymer nanocomposites. The flue gas containing a complex mixture of combustion gases and particles is characterized by different particle analysers, PAH analysis, VOC analysis and TEM. The biological impact is studied by using a VITROCELL Automated ALI exposure station. Hereby, cells of the adenocarcino cell line A549 as well as a reconstituted bronchial epithelium (MucilAir, Epithelix) were exposed for 4 hours to the aerosols emitted from the combustion process. Within the exposure process, cells were exposed to the native aerosol, an aerosol under conditions to increase particle deposition via high voltage as well as a filtered aerosol, and therefore the sole gaseous phase. Furthermore, each exposure included a so-called clean air control, where cells where exposed to filtered air. The exposure was followed by a 21 h post-incubation before the cytotoxic effects were determined via LDH-release. To reveal if possible adverse effects are caused by the used nano-scaled filling material, all used nanomaterials did also undergo the same combustion process as a single material. Cytotoxicity studies showed no increased cytotoxic effects after the combustion of the sole nano-scaled filling materials. However, combustion of PE containing materials resulted in an enhanced LDH-release, and therefore cytotoxicity, in both cell culture models. Since no difference between exposures of unfiltered and filtered aerosols was apparent, it suggested that the observed cytotoxicity is due to the combustion induced gaseous phase

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists