Integration of adult patients with phenylketonuria into professional life: long-term follow-up of 27 patients in a single centre in Switzerland

BACKGROUND Neonatal screening and treatment of phenylketonuria (PKU) prevent the development of neurocognitive impairment. The degree of dysfunction may be related to metabolic control and responsible for a hampered school career. METHODS This was a retrospective study from a single metabolic unit of a Swiss University Hospital. The time point of diagnosis and all Phenylalanin (Phe) concentrations during the follow-up were recorded. The primary outcome was integration into professional life defined as no professional studies versus accomplished apprenticeship versus high school diploma/university. Phe levels were correlated with professional outcome. The control group consisted of the patients' healthy parents and siblings. RESULTS A total of 27 patients (13 females, 14 males) were included in the study. The mean (SD) follow-up period was 25.1 (7.6) years. The control group consisted of 57 subjects. Overall, 23 patients were diagnosed by neonatal screening, and 4 patients were diagnosed later. All 4 were in the non-professional study group. Compared with the controls there were significantly more patients in the non-professional study group (26% vs 9%, p <0.05) and significantly less in the accomplished apprenticeship group (59% vs 82%; p <0.04). After exclusion of the patients with late diagnosis no significant differences were found with regard to the professional integration between patients and controls. Significant differences in Phe-levels between the three groups could be documented between 2-10 years of age with the highest levels in the non-professional study followed by the accomplished apprenticeship and the high school diploma group (p <0.01). CONCLUSION Patients who are diagnosed by neonatal screening and are consequently cared for are able to accomplish an apprenticeship or a high school diploma.

Evaluation of Swiss slaughterhouse data for integration in a syndromic surveillance system

BACKGROUND: We evaluated Swiss slaughterhouse data for integration in a national syndromic surveillance system for the early detection of emerging diseases in production animals. We analysed meat inspection data for cattle, pigs and small ruminants slaughtered between 2007 and 2012 (including emergency slaughters of sick/injured animals); investigating patterns in the number of animals slaughtered and condemned; the reasons invoked for whole carcass condemnations; reporting biases and regional effects. RESULTS: Whole carcass condemnation rates were fairly uniform (1-2‰) over time and between the different types of production animals. Condemnation rates were much higher and less uniform following emergency slaughters. The number of condemnations peaked in December for both cattle and pigs, a time when individuals of lower quality are sent to slaughter when hay and food are limited and when certain diseases are more prevalent. Each type of production animal was associated with a different profile of condemnation reasons. The most commonly reported one was "severe lesions" for cattle, "abscesses" for pigs and "pronounced weight loss" for small ruminants. These reasons could constitute valuable syndromic indicators as they are unspecific clinical manifestations of a large range of animal diseases (as well as potential indicators of animal welfare). Differences were detected in the rate of carcass condemnation between cantons and between large and small slaughterhouses. A large percentage (>60% for all three animal categories) of slaughterhouses operating never reported a condemnation between 2007 and 2012, a potential indicator of widespread non-reporting bias in our database. CONCLUSIONS: The current system offers simultaneous coverage of cattle, pigs and small ruminants for the whole of Switzerland; and traceability of each condemnation to its farm of origin. The number of condemnations was significantly linked to the number of slaughters, meaning that the former should be always be offset by the later in analyses. Because this denominator is only communicated at the end of the month, condemnations may currently only be monitored on a monthly basis. Coupled with the lack of timeliness (30-60 days delay between condemnation and notification), this limits the use of the data for early-detection.

Penetrability of the inner mucus layer: who is out there?

Large numbers of microorganisms colonise the skin and mucous membranes of animals, with their highest density in the lower gastrointestinal tract. The impact of these microbes on the host can be demonstrated by comparing animals (usually mice) housed under germ-free conditions, or colonised with different compositions of microbes. Inbreeding and embryo manipulation programs have generated a wide variety of mouse strains with a fixed germ-line (isogenic) and hygiene comparisons robustly show remarkably strong interactions between the microbiota and the host, which can be summarised in three axioms. (I) Live microbes are largely confined to their spaces at body surfaces, provided the animal is not suffering from an infection. (II) There is promiscuous molecular exchange throughout the host and its microbiota in both directions [1]. (III) Every host organ system is profoundly shaped by the presence of body surface microbes. It follows that one must draw a line between live microbial and host “spaces” (I) to understand the crosstalk (II and III) at this interesting interface of the host-microbial superorganism. Of course, since microbes can adapt to very different niches, there has to be more than one line. In this issue of EMBO Reports, Johansson and colleagues have studied mucus, which is the main physical frontier for most microbes in the intestinal tract: they report how different non-pathogenic microbiota compositions affect its permeability and the functional protection of the epithelial surface [2].

Dysfunction of Cortical Dendritic Integration in Neuropathic Pain Reversed by Serotoninergic Neuromodulation

Neuropathic pain is caused by long-term modifications of neuronal function in the peripheral nervous system, the spinal cord, and supraspinal areas. Although functional changes in the forebrain are thought to contribute to the development of persistent pain, their significance and precise subcellular nature remain unexplored. Using somatic and dendritic whole-cell patch-clamp recordings from neurons in the anterior cingulate cortex, we discovered that sciatic nerve injury caused an activity-dependent dysfunction of hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels in the dendrites of layer 5 pyramidal neurons resulting in enhanced integration of excitatory postsynaptic inputs and increased neuronal firing. Specific activation of the serotonin receptor type 7 (5-HT7R) alleviated the lesion-induced pathology by increasing HCN channel function, restoring normal dendritic integration, and reducing mechanical pain hypersensitivity in nerve-injured animals in vivo. Thus, serotoninergic neuromodulation at the forebrain level can reverse the dendritic dysfunction induced by neuropathic pain and may represent a potential therapeutical target.

3D documentation and visualization of external injury findings by integration of simple photography in CT/MRI data sets (IprojeCT).

This study evaluated the feasibility of documenting patterned injury using three dimensions and true colour photography without complex 3D surface documentation methods. This method is based on a generated 3D surface model using radiologic slice images (CT) while the colour information is derived from photographs taken with commercially available cameras. The external patterned injuries were documented in 16 cases using digital photography as well as highly precise photogrammetry-supported 3D structured light scanning. The internal findings of these deceased were recorded using CT and MRI. For registration of the internal with the external data, two different types of radiographic markers were used and compared. The 3D surface model generated from CT slice images was linked with the photographs, and thereby digital true-colour 3D models of the patterned injuries could be created (Image projection onto CT/IprojeCT). In addition, these external models were merged with the models of the somatic interior. We demonstrated that 3D documentation and visualization of external injury findings by integration of digital photography in CT/MRI data sets is suitable for the 3D documentation of individual patterned injuries to a body. Nevertheless, this documentation method is not a substitution for photogrammetry and surface scanning, especially when the entire bodily surface is to be recorded in three dimensions including all external findings, and when precise data is required for comparing highly detailed injury features with the injury-inflicting tool.

An Application-Layer RESTful Sleepy Nodes Implementation For Internet of Things Systems

Two of the main issues in wireless industrial Internet of Things applications are interoperability and network lifetime. In this work we extend a semantic interoperability platform and introduce an application-layer sleepy nodes protocol that can leverage on information stored in semantic repositories. We propose an integration platform for managing the sleep states and an application layer protocol based upon the Constraint Application Layer protocol. We evaluate our system on windowing based task allocation strategies, aiming for lower overall energy consumption that results in higher network lifetime.

Fine-grained Indoor Tracking by Fusing Inertial Sensor and Physical Layer Information in WLANs

Indoor positioning has become an emerging research area because of huge commercial demands for location-based services in indoor environments. Channel State Information (CSI) as a fine-grained physical layer information has been recently proposed to achieve high positioning accuracy by using range-based methods, e.g., trilateration. In this work, we propose to fuse the CSI-based ranges and velocity estimated from inertial sensors by an enhanced particle filter to achieve highly accurate tracking. The algorithm relies on some enhanced ranging methods and further mitigates the remaining ranging errors by a weighting technique. Additionally, we provide an efficient method to estimate the velocity based on inertial sensors. The algorithms are designed in a network-based system, which uses rather cheap commercial devices as anchor nodes. We evaluate our system in a complex environment along three different moving paths. Our proposed tracking method can achieve 1:3m for mean accuracy and 2:2m for 90% accuracy, which is more accurate and stable than pedestrian dead reckoning and range-based positioning.

Granular layer in the periplasmic space of gram-positive bacteria and fine structures of Enterococcus gallinarum and Streptococcus gordonii septa revealed by cryo-electron microscopy of vitreous sections.

High-resolution structural information on optimally preserved bacterial cells can be obtained with cryo-electron microscopy of vitreous sections. With the help of this technique, the existence of a periplasmic space between the plasma membrane and the thick peptidoglycan layer of the gram-positive bacteria Bacillus subtilis and Staphylococcus aureus was recently shown. This raises questions about the mode of polymerization of peptidoglycan. In the present study, we report the structure of the cell envelope of three gram-positive bacteria (B. subtilis, Streptococcus gordonii, and Enterococcus gallinarum). In the three cases, a previously undescribed granular layer adjacent to the plasma membrane is found in the periplasmic space. In order to better understand how nascent peptidoglycan is incorporated into the mature peptidoglycan, we investigated cellular regions known to represent the sites of cell wall production. Each of these sites possesses a specific structure. We propose a hypothetic model of peptidoglycan polymerization that accommodates these differences: peptidoglycan precursors could be exported from the cytoplasm to the periplasmic space, where they could diffuse until they would interact with the interface between the granular layer and the thick peptidoglycan layer. They could then polymerize with mature peptidoglycan. We report cytoplasmic structures at the E. gallinarum septum that could be interpreted as cytoskeletal elements driving cell division (FtsZ ring). Although immunoelectron microscopy and fluorescence microscopy studies have demonstrated the septal and cytoplasmic localization of FtsZ, direct visualization of in situ FtsZ filaments has not been obtained in any electron microscopy study of fixed and dehydrated bacteria.

RETINAL LAYER RESPONSE TO RANIBIZUMAB DURING TREATMENT OF DIABETIC MACULAR EDEMA: Thinner is Not Always Better.

PURPOSE To identify individual retinal layer thickness changes associated with visual acuity gain in diabetic macular edema treated with ranibizumab using layer segmentation on high-resolution optical coherence tomography scans. METHODS Retrospective observational case series. Thirty-three treatment-naive eyes with diabetic macular edema were imaged by spectral domain optical coherence tomography at monthly visits while receiving intravitreal ranibizumab treatment as needed, guided by visual acuity. Thickness changes of individual layers after 1 year were quantitatively analyzed and correlated with visual acuity gain. RESULTS The mean best-corrected visual acuity improvement at 1 year was 6.2 (SEM ± 1.5) Early Treatment Diabetic Retinopathy Study letters, and central retinal thickness decreased by 66 ± 18 μm. In the central subfield, there was a significant decrease of thickness for all layers (P < 0.05) except the outer nuclear layer. Multiple linear regression analysis revealed that thickness decrease of the inner retina was associated with better visual acuity, whereas for the outer retina the opposite was true. The best estimate of final visual acuity (R = 0.817, P < 0.001) was obtained, by including baseline visual acuity and thickness change of the inner and outer plexiform layers in the model. CONCLUSION Whereas thickness decrease of the inner retina was positively associated with visual acuity gain, the opposite was found for the outer retina. This might be indirect evidence for recovery of the outer retina during ranibizumab treatment.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Fine-grained Indoor Tracking by Fusing Inertial Sensor and Physical Layer Information in WLANs

Indoor positioning has become an emerging research area because of huge commercial demands for location-based services in indoor environments. Channel State Information (CSI) as fine-grained physical layer information has been recently proposed to achieve high positioning accuracy by using range based methods, e.g., trilateration. In this work, we propose to fuse the CSI-based ranging and velocity estimated from inertial sensors by an enhanced particle filter to achieve highly accurate tracking. The algorithm relies on some enhanced ranging methods and further mitigates the remaining ranging errors by a weighting technique. Additionally, we provide an efficient method to estimate the velocity based on inertial sensors. The algorithms are designed in a network-based system, which uses rather cheap commercial devices as anchor nodes. We evaluate our system in a complex environment along three different moving paths. Our proposed tracking method can achieve 1.3m for mean accuracy and 2.2m for 90% accuracy, which is more accurate and stable than pedestrian dead reckoning and range-based positioning.

Characterising the three-dimensional ozone distribution of a tidally locked Earth-like planet

We simulate the 3D ozone distribution of a tidally locked Earth-like exoplanet using the high-resolution, 3D chemistry climate model CESM1(WACCM) and study how the ozone layer of a tidally locked Earth (TLE) (ΩTLE = 1/365 days) differs from that of our present-day Earth (PDE) (ΩPDE = 1/1 day). The middle atmosphere reaches a steady state a symptotically within the first 80 days of the simulation. An upwelling, centred on the subsolar point, is present on the day side while a downwelling, centred on the antisolar point, is present on the night side. In the mesosphere, we find similar global ozone distributions for the TLE and the PDE, with decreased ozone on the day side and enhanced ozone on the night side. In the lower mesosphere, a jet stream transitions into a large-scale vortex around a low-pressure system, located at low latitudes of the TLE night side. In the middle stratosphere, the concentration of odd oxygen is approximately equal to that of the ozone [(Ox) ≈ (O3)]. At these altitudes, the lifetime of odd oxygen is ~16 h and the transport processes significantly contribute to the global distribution of stratospheric ozone. Compared to the PDE, where the strong Coriolis force acts as a mixing barrier between low and high latitudes, the transport processes of the TLE are governed by jet streams variable in the zonal and meridional directions. In the middle stratosphere of the TLE, we find high ozone values on the day side, due to the increased production of atomic oxygen on the day side, where it immediately recombines with molecular oxygen to form ozone. In contrast, the ozone is depleted on the night side, due to changes in the solar radiation distribution and the presence of a downwelling. As a result of the reduced Coriolis force, the tropical and extratropical air masses are well mixed and the global temperature distribution of the TLE stratosphere has smaller horizontal gradients than the PDE. Compared to the PDE, the total ozone column global mean is reduced by ~19.3 %. The day side and the night side total ozone column means are reduced by 23.21 and 15.52 %, respectively. Finally, we present the total ozone column (TOC) maps as viewed by a remote observer for four phases of the TLE during its revolution around the star. The mean TOC values of the four phases of the TLE vary by up to 23 %.