Nanoscale assembly processes revealed in the nacroprismatic transition zone of Pinna nobilis mollusc shells

Intricate biomineralization processes in molluscs engineer hierarchical structures with meso-, nano-, and atomic architectures that give the final composite material exceptional mechanical strength and optical iridescence on the macroscale. This multiscale biological assembly inspires new synthetic routes to complex materials. Our investigation of the prism-nacre interface reveals nanoscale details governing the onset of nacre formation using high-resolution scanning transmission electron microscopy. A wedge polishing technique provides unprecedented, large-area specimens required to span the entire interface. Within this region, we find a transition from nanofibrillar aggregation to irregular early-nacre layers, to well-ordered mature nacre suggesting the assembly process is driven by aggregation of nanoparticles (~50-80 nm) within an organic matrix that arrange in fiber-like polycrystalline configurations. The particle number increases successively and, when critical packing is reached, they merge into early-nacre platelets. These results give new insights into nacre formation and particle-accretion mechanisms that may be common to many calcareous biominerals.Comment: 5 Figure

Evaluation of non-chemical seed treatment methods for the control of Alternaria dauci and A. radicina on carrot seeds

The current study was initiated to evaluate the efficacy of physical methods (hot water, aerated steam, electron treatment) and agents of natural origin (resistance inducers, plant derived products, micro-organisms) as seed treatments of carrots for control of Alternaria dauci and A. radicina. Control of both Alternaria species by seed treatment with the resistance inducers was generally poor. Results were also not satisfactory with most of the formulated commercial micro-organism preparations. Based on the average of five field trials, one of these, BA 2552 (Pseudomonas chlororaphis), provided a low but significant increase in plant stand. Among the experimental micro-organisms, the best results were obtained with Pseudomonas sp. strain MF 416 and Clonostachys rosea strain IK726. A similar level of efficacy was provided by seed treatment with an emulsion (1%) of thyme oil in water. Good and consistent control was generally achieved with the physical methods aerated steam, hot water and electron treatment. Aerated steam treatment was, apart from the thiram-containing chemical standard, the best single treatment, and its performance may at least partially be due to extensive pre-testing, resulting in dosages optimally adapted to the respective seed lot. In some of the experiments the effect of the hot water treatment, which was tested at a fixed, not specifically adapted dosage, was significantly improved when combined with a Pseudomonas sp. MF 416 or C. rosea IK726 treatment. The results are discussed in relation to the outcome of experiments in which the same seed treatment methods and agents were tested in other seed-borne vegetable pathosystems

The rainbow cohort: 96 week follow-up of saquinavir-containing regimens in previously antiretroviral therapy (ART)-naïve and pre-treated but protease inhibitor (PI)- naïve hiv-infected patients

<p>Abstract</p> <p>Objective</p> <p>We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients treated in a long-term one line (96 weeks) follow-up of the initial study.</p> <p>Methods</p> <p>All ART-and PI-naïve patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis.</p> <p>Results</p> <p>The analysis included 175 ART-naïve and 109 pretreated but PI-naïve patients. After 96 weeks, a similar proportion of patients in the ART-naïve and in the pretreated but Pi-naïve group had HIV-1 RNA levels < 400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA < 50 copies/mL was higher in the ART-naïve group compared with the pretreated but PI-naïve group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was'+263 cells/mm³(IQR 170; 384. LOCF; p < 0.0001) in the ART-naïve group, and one line +181 cells/mm³(IQR 60; 309. LOCF; p < 0.0001) in the pretreated but PI-naïve group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low-and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naïve and pretreated patients.</p> <p>Conclusions</p> <p>This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naïve and pretreated but PI-naïve patients in the real-life clinical setting.</p

Stability of Drugs Stored in Helicopters for Use by Emergency Medical Services: A Prospective Observational Study.

STUDY OBJECTIVE Drugs stored in rescue helicopters may be subject to extreme environmental conditions. The aim of this study was to measure whether drugs stored under the real-life conditions of a Swiss helicopter emergency medical service (HEMS) would retain their potency over the course of 1 year. METHODS A prospective, longitudinal study measuring the temperature exposure and concentration of drugs stored on 2 rescue helicopters in Switzerland over 1 year. The study drugs included epinephrine, norepinephrine, amiodarone, midazolam, fentanyl, naloxone, rocuronium, etomidate, and ketamine. Temperatures were measured inside the medication storage bags and the crew cabins at 10-minute intervals. Drug stability was measured on a monthly basis over the course of 12 months using high-performance liquid chromatography. The medications were considered stable at a minimum remaining drug concentration of 90% of the label claim. RESULTS Temperatures ranged from -1.2 °C to 38.1 °C (29.84 °F to 100.58 °F) inside the drug storage bags. Of all the temperature measurements inside the drug storage bags, 37% lay outside the recommended storage conditions. All drugs maintained a concentration above 90% of the label claim. The observation periods for rocuronium and etomidate were shortened to 7 months because of a supply shortage of reference samples. CONCLUSION Drugs stored under the real-life conditions of Swiss HEMS are subjected to temperatures outside the manufacturer's approved storage requirements. Despite this, all drugs stored under these conditions remained stable throughout our study. Real-life stability testing could be a way to extend drug exchange intervals

Differences in the use of surface water resources by desert birds are revealed using isotopic tracers

The scarcity of free-standing water sources is a key determinant of animal and plant community structure in arid environments, and an understanding of the extent to which particular species use surface water is vital for modeling the effects of climate change on desert avifauna. We investigated interspecific variation in the use of artificial water sources among birds in the Kalahari Desert, South Africa, by (i) observations at waterholes and (ii) tracing spatial water-use patterns during summer by isotopically labeled water sources and blood sampling. More than 50% of the avian community (primarily insectivores and omnivores) were not observed to drink. The majority (53%) of species drinking at waterholes were granivorous, and their use of surface water was best predicted by their relative abundance in the community. Species representing the remaining dietary guilds drank significantly more on hot days. Blood samples revealed that only 11 of 42 species (mostly granivores and a few omnivores) showed evidence of drinking at a waterhole with enriched deuterium values; on average, in the latter birds, water from the enriched waterhole accounted for ~38% of their body water pool. These findings illustrate that 2 methods employed in this study provide different, but complementary data on the relative importance of a water source for an avian community. Although our results suggest that most avian species are independent of surface water, drinking patterns on the hottest days during our study period suggest that free-standing water might become more important for some of the non-drinking species under hotter climatic conditions

Phylogeographic reconstruction of the marbled crayfish origin

The marbled crayfish (Procambarus virginalis) is a triploid and parthenogenetic freshwater crayfish species that has colonized diverse habitats around the world. Previous studies suggested that the clonal marbled crayfish population descended as recently as 25 years ago from a single specimen of P. fallax, the sexually reproducing parent species. However, the genetic, phylogeographic, and mechanistic origins of the species have remained enigmatic. We have now constructed a new genome assembly for P. virginalis to support a detailed phylogeographic analysis of the diploid parent species, Procambarus fallax. Our results strongly suggest that both parental haplotypes of P. virginalis were inherited from the Everglades subpopulation of P. fallax. Comprehensive whole-genome sequencing also detected triploid specimens in the same subpopulation, which either represent evolutionarily important intermediate genotypes or independent parthenogenetic lineages arising among the sexual parent population. Our findings thus clarify the geographic origin of the marbled crayfish and identify potential mechanisms of parthenogenetic speciation

Safety and efficacy after switch to a saquinavir-containing antiretroviral regimen in protease inhibitor pretreated HIV-positive patients

<p>Abstract</p> <p>Objective</p> <p>The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naïve patients.</p> <p>Methods</p> <p>Multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48.</p> <p>Results</p> <p>A total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels < 50 copies/mL at week 48 was 60.3% (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm³from baseline (p < 0.01) and 60.3% of patients achieved HIV-1 RNA < 50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride < 200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR 1024; 0) for baseline triglyceride > 750 mg/dL (p < 0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC < 200 mg/dL (p < 0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC > 300 mg/dL (p < 0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects.</p> <p>Conclusions</p> <p>These data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naïve patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.</p

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia