Reflecting on the reasons pros and cons coercive measures for patients in psychiatric and somatic care: The role of clinical ethics consultation. A pilot study

Background and aim: Coercive measures in patient care have come under criticism leading to implement guidelines dedicated to the reduction of coercion. This development of bringing to light clinical ethics support is hoped to serve as a means of building up awareness and potentially reducing the use of coercion. This study explores the specific features of ethics consultation (EC) while dealing with coercion. Material and method: Basel EC documentation presents insight to all persons involved with a case. The EC database of two Basel university hospitals was developed on the grounds of systematic screening and categorization by two reviewers. One hundred fully documented EC cases databased from 2013 to 2016 were screened for the discussion of coercive measures (somatic hospital and psychiatry: 50% cases). Results: Twenty-four out of 100 EC cases addressed coercion in relation to a clinically relevant question, such as compulsory treatment (70.8%), involuntary committal (50%), or restricting liberty (16.6%). Only 58.3% of EC requests mentioned coercion as an ethical issue prior to the meeting. In no case was patient decisional capacity given, capacity was impaired (43.5%), not given (33.3%), or unclear (21.7%; one not available). Discussion: As clinical staff appears sensitive to perceiving ethical uncertainty or conflict, but less prepared to articulate ethical concern, EC meetings serve to "diagnose" and "solve" the ethical focus of the problem(s) presented in EC. Patient decisional incapacity proved to be an important part of reasoning, when discussing the principle of harm prevention. While professional judgment of capacity remains unsystematic, rationality or even ethicality of decision making will be hampered. The documented EC cases show a variety of decisions about whether or not coercion was actually applied. Ethical reasoning on the competing options seemed to be instrumental for an unprejudiced decision complying with the normative framework and for building a robust consensus. Conclusions: The recommendation is whether EC should be used as a standard practice whenever coercion is an issue-ideally before coercion is applied, or otherwise. Moreover, more efforts should be made toward early and professional assessment of patient capacity and advance care counseling including the offer of advance directives

Competing electric and magnetic excitations in backward electron scattering from heavy deformed nuclei

Important $E2$ contributions to the $(e,e^{\prime})$ cross sections of low-lying orbital $M1$ excitations are found in heavy deformed nuclei, arising from the small energy separation between the two excitations with $I^{\pi}K = 2^+1$ and 1$^+1$, respectively. They are studied microscopically in QRPA using DWBA. The accompanying $E2$ response is negligible at small momentum transfer $q$ but contributes substantially to the cross sections measured at $\theta = 165 ^{\circ}$ for $0.6 < q_{\rm eff} < 0.9$ fm$^{-1}$ ($40 \le E_i \le 70$ MeV) and leads to a very good agreement with experiment. The electric response is of longitudinal $C2$ type for $\theta \le 175 ^{\circ}$ but becomes almost purely transverse $E2$ for larger backward angles. The transverse $E2$ response remains comparable with the $M1$ response for $q_{\rm eff} > 1.2$ fm$^{-1}$ ($E_i > 100$ MeV) and even dominant for $E_i > 200$ MeV. This happens even at large backward angles $\theta > 175 ^{\circ}$, where the $M1$ dominance is limited to the lower $q$ region.Comment: RevTeX, 19 pages, 8 figures included Accepted for publication in Phys Rev

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Small molecule probes of protein aggregation

Understanding the mechanisms of amyloid formation and toxicity remain major challenges. Whilst substantial progress has been made in the development of methods able to identify the species formed during self-assembly and to describe the kinetic mechanisms of aggregation, the structure(s) of non-native species, including potentially toxic oligomers, remain elusive. Moreover, how fibrils contribute to disease remains unclear. Here we review recent advances in the development of small molecules and other reagents that are helping to define the mechanisms of protein aggregation in molecular detail. Such probes form a powerful platform with which to better define the mechanisms of structural conversion into amyloid fibrils and may provide the much-needed stepping stone for future development of successful therapeutic agents

SPE-44 Implements Sperm Cell Fate

The sperm/oocyte decision in the hermaphrodite germline of Caenorhabditis elegans provides a powerful model for the characterization of stem cell fate specification and differentiation. The germline sex determination program that governs gamete fate has been well studied, but direct mediators of cell-type-specific transcription are largely unknown. We report the identification of spe-44 as a critical regulator of sperm gene expression. Deletion of spe-44 causes sperm-specific defects in cytokinesis, cell cycle progression, and organelle assembly resulting in sterility. Expression of spe-44 correlates precisely with spermatogenesis and is regulated by the germline sex determination pathway. spe-44 is required for the appropriate expression of several hundred sperm-enriched genes. The SPE-44 protein is restricted to the sperm-producing germline, where it localizes to the autosomes (which contain sperm genes) but is excluded from the transcriptionally silent X chromosome (which does not). The orthologous gene in other Caenorhabditis species is similarly expressed in a sex-biased manner, and the protein likewise exhibits autosome-specific localization in developing sperm, strongly suggestive of an evolutionarily conserved role in sperm gene expression. Our analysis represents the first identification of a transcriptional regulator whose primary function is the control of gamete-type-specific transcription in this system

Human somatosensory area 2 : observer-independent cytoarchitectonic mapping, interindividual variability and population map

We analyzed the topographical variability of human somatosensory area 2 in 10 postmortem brains. The brains were serially sectioned at 20 microm, and sections were stained for cell bodies. Area 2 was delineated with an observer-independent technique based on significant differences in the laminar densities of cell bodies. The sections were corrected with an MR scan of the same brain obtained before histological processing. Each brain's histological volume and representation of area 2 was subsequently reconstructed in 3-D. We found that the borders of area 2 are topographically variable. The rostral border lies between the convexity of the postcentral gyrus and some millimeters deep in the rostral wall of the postcentral sulcus. The caudal border lies between the fundus of the postcentral sulcus and some millimeters above it in the rostral wall. In contrast to Brodmann's map, area 2 does not extend onto the mesial cortical surface or into the intraparietal sulcus. When the postcentral sulcus is interrupted by a gyral bridge, area 2 crosses this bridge and is not separated into two segments. After cytoarchitectonic analysis, the histological volumes were warped to the reference brain of a computerized atlas and superimposed. A population map was generated in 3-D space, which describes how many brains have a representation of area 2 in a particular voxel. This microstructurally defined population map can be used to demonstrate activations of area 2 in functional imaging studies and therefore help to further understand the role of area 2 in somatosensory processing

Comparison of spatial normalization procedures and their impact on functional maps

The alignment accuracy and impact on functional maps of four spatial normalization procedures have been compared using a set of high resolution brain MRIs and functional PET volumes acquired in 20 subjects. Simple affine (AFF), fifth order polynomial warp (WRP), discrete cosine basis functions (SPM), and a movement model based on full multi grid (FMG) approaches were applied on the same dataset for warping individual volumes onto the Human Brain Atlas (HBA) template. Intersubject averaged structural volumes and tissue probability maps were compared across normalization methods and to the standard brain. Thanks to the large number of degrees of freedom of the technique, FMG was found to provide enhanced alignment accuracy as compared to the other three methods, both for the grey and white matter tissues; WRP and SPM exhibited very similar performances whereas AFF had the lowest registration accuracy. SPM, however, was found to perform better than the other methods for the intra-cerebral cerebrospinal fluid (mainly in the ventricular compartments). Limited differences in terms of activation morphology and detection sensitivity were found between low resolution functional maps (FWHM approximately 10 mm) spatially normalized with the four methods, which overlapped in 42.8% of the total activation volume. These findings suggest that the functional variability is much larger than the anatomical one and that precise alignment of anatomical features has low influence on the resulting intersubject functional maps. When increasing the spatial resolution to approximately 6 mm, however, differences in localization of activated areas appear as a consequence of the different spatial normalization procedure used, restricting the overlap of the normalized activated volumes to only 6.2%