Measurement of the Isolated Nuclear Two-Photon Decay in

The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to ∼100 keV and half-lives as short as ∼10 ms. The half-life for the 2γ decay of the first-excited 0^{+} state in bare ^{72}Ge ions was determined to be 23.9(6) ms, which strongly deviates from expectations.

Effectiveness of supported housing versus residential care in severe mental illness: a multicenter, quasi-experimental study.

PURPOSE: Up to now there are only few studies and no RCT comparing efficacy or effectiveness of supported housing (SH) versus residential care (RC) in severe mental illness (SMI) without homelessness. Here we present an observational follow-up study in SMI subjects, who entered SH or RC, to compare clinical and functional outcomes 2 years later. METHODS: In this prospective study in more than 30 locations throughout a German federal state, we included SMI subjects, who entered SH (n = 153) or RC (n = 104). About one quarter suffered from each substance use, psychotic, affective, or other disorders. To avoid sampling bias, we used the propensity score matching method to establish a quasi-experimental design. Outcome measures were social functioning (SFS), the number of psychiatric hospitalisations, psychopathology (SCL-9-K), and quality of life (MANSA). Apart from descriptive methods we analysed primarily using repeated-measures ANOVAS. RESULTS: Our analyses revealed significant effects of time for all outcomes in both study groups. However, there were not any group differences of outcome measures, i.e., not any significant effects of group or interactional effects of group x time. Moreover, these results hold true for intent-to-treat and per-protocol sample analyses. CONCLUSION: The results show, that SH and RC for non-homeless people with SMI achieve the same clinical and psychosocial outcomes across a 2-year period. Taking into account the users' preferences, the present findings should give reason to ensure the availability of affordable housing and to support the expansion of supported housing approaches.

[Genotype-Phenotype Correlations in Patients with CRB1 Mutations]. / Genotyp-Phänotyp-Korrelation bei Patienten mit CRB1-Mutationen.

Background Mutations in the CRB1 gene were identified in patients with early-onset severe retinal dystrophy (EOSRD), childhood-onset and juvenile-onset rod-cone dystrophy. This study describes the phenotypic spectrum of disease-causing CRB1-mutations in the first two decades of life. Materials and Methods Eight patients, aged three months to 20 years, underwent a full comprehensive ophthalmological examination including best corrected visual acuity testing (BCVA), color vision testing, funduscopy, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) recording. Automated and manual retinal layer segmentation of SD-OCT recordings was performed using DIOCTA software. A full-field electroretinography (ffERG, ISCEV Standard) and visual fields were performed in cooperative patients. Results Five patients carried mutations causing a loss of the corresponding gene product (splice-mutation, nonsense-mutation, frame-shifting mutation). These patients presented with generally reduced vision in the first months of life that never exceeded 0.04 during the observational period. The sixth patient carried a homozygous missense mutation and reached maximal BCVA 0.05 at the age of 6 years. Two further patients, carrying at least one hypomorphic missense-mutation, presented with better preserved visual function with up to 0.5 at the age of 20 years. The recorded ffERG was below threshold in the majority of patients. Visual fields were severely restricted. The photoreceptor layers were significantly reduced in SD-OCT whenever stratification of retinal layers was possible. The inner nuclear layer thickness increased with progressing retinal degeneration. A-Scan analysis revealed better preservation of the retinal stratification in patients with missense mutations. Conclusions Patients with CRB1-mutations presented with a severe phenotype with severely reduced visual acuity from birth. Missense mutations with predicted residual function of the gene product were associated with moderate expression of the disease. Severe and progressive restriction of visual fields occurred in the first decade of life. The reduced retinal stratification indicates a general loss of structural integrity of the retinal layers.

[Indication and Results of the Anderson Procedure]. / Indikation und Ergebnisse der Anderson-Operation.

The major goal of extraocular muscle surgery for nystagmus is to reduce the abnormal head turn (AHT) which is caused by an eccentric null zone of the nystagmus. Shifting the null zone to the primary gaze position will eliminate the AHT. The Kestenbaum procedure consists of bilateral recession of the yoke muscles opposite to the AHT, combined with bilateral resection or plication of their antagonists. The Anderson procedure is confined to bilateral recession of the yoke muscles and is therefore less invasive. We report on our experience with the Anderson procedure. Patients and Methods: From September 2013 to June 2015, we performed the Anderson procedure in 11 consecutive orthotropic patients with infantile idiopathic or sensory defect nystagmus. Patients responsive to convergence inducing prisms who could benefit from artificial divergence surgery were excluded. Results: Medians and ranges (minimum-maximum) were: Age 7 years (4-30); binocular BCVA 0.5 (0.05-1.0); AHT 30° (20-40); equal recessions on the horizontal yoke muscles opposite to the AHT of 12 mm (10-17), in one case using bovine pericardium grafts. Three (3-6) months post surgery, the AHT was reduced to 7° (0-20). First step success rates, defined by residual AHT ≤ 10° and ≤ 15°, were 73 % (95 % CI 39-93 %) and 82 % (95 % CI 48-97 %). No over-correction or other adverse effects were observed. Two patients later received augmenting surgery. One patient with pre-existing exophoria later required strabismus surgery for exotropia. Conclusion: The AHT can be significantly reduced or completely corrected by the Anderson procedure. Recessions of at least 10 mm on both yoke muscles were performed. The success rates equaled success rates of augmented Kestenbaum surgery. Compared to the latter, the Anderson procedure is less invasive. It is followed by a shorter healing process. It is a vessel sparing method - an advantage for potential future surgery.

[Albinism and the Range of Fundus Hypopigmentation, Macular Hypoplasia, and Nystagmus]. / Albinimus und das Spektrum der Fundushypopigmentierung, der Makulahypoplasie und des Nystagmus.

From the ophthalmological view, albinism is a disorder of reduced pigmentation of the retinal and irdial pigment epithelium and the iris and choroid stroma. The reduced pigmentation is accompanied by morphological changes in the retina and the optic nerve. The functional relationship of these morphological changes is not yet well understood. This review summarises the genetic causes of reduced pigment synthesis and impaired pigment distribution, and discusses the variability of expression of albinism symptoms, in the light of other disorders affecting retinal development.

[Treatment Options for Basal Cell Carcinomas of the Medial Canthus]. / Therapieoptionen bei Basalzellkarzinomen des medialen Lidwinkels.

Basal cell carcinoma is the most common skin cancer of the eyelid. It most frequently occurs on the lower eyelid and the medial canthus. Although metastases appear only very rarely, basal cell carcinoma is locally destructive if left untreated. Nowadays several surgical and nonsurgical treatments can be used to remove or destroy basal cell carcinomas. The selection of optimal treatment depends on the initial individual situation as well as the age and the general condition of the patient. The "gold standard" method for the treatment of basal cell carcinomas is surgical removal with subsequent histological examination. Because of the complex anatomical characteristics of the medial canthus and the lateral nasal root region, basal cell carcinomas of this area present great challenges for any treatment method. These characteristics also explain the higher rates of incomplete removal and greater risk of recurrence, with in depth extension of the tumor. Additionally, surgical removal of the tumor from the medial canthus area often results in extended tissue defects. The plastic covering of these defects can be achieved by various reconstruction procedures.

[Handheld Optical Coherence Tomography in Paediatric Ophthalmology: Experience of the Department of Ophthalmology in Giessen]. / Handgehaltene optische Kohärenztomografie in pädiatrischer Ophthalmologie: Erfahrung der Gießener Universitätsaugenklinik.

Introduction: Optical coherence tomography is an important tool for the imaging and analysis of retinal structures. The usability of conventional table-top devices is limited in children. We report on our experiences with a handheld Spectral Domain Optical Coherence Tomography (HH-SD-OCT, Bioptigen™) in infants and young children in our daily practice. Methods: Between October 2014 and April 2016, we investigated 259 patients. Indications and diagnoses were assessed. Individual examples are shown to demonstrate the advantages and disadvantages of the novel technique. Results: It was possible to examine 259 children of at least 7 weeks of age (median: 1.59 years; ± 1.32 SD) with a mean investigation time of 18.3 minutes (± 8.3 SD). The most frequent indication was retinal assessment in prematures (32.8 %). Nystagmus, retinal dystrophies, reduced visual acuity and albinism amounted to additional 37.4 % of all indications. Conclusions: Handheld OCT is a beneficial complement for diagnosis of diseases in paediatric ophthalmology. As a complement to established methods like wide-field fundus photography, HH-SD-OCT allows the physician to assess and follow-up new objective structural information. As the Bioptigen does not have an eye tracker, it is challenging to orient the scan in the posterior retinal pole, in particular in case of instable fixation. This complicates follow-up investigations, which can only be performed with additional high programming and analysis effort.

Rubber friction on road surfaces: Experiment and theory for low sliding speeds.

We study rubber friction for tire tread compounds on asphalt road surfaces. The road surface topographies are measured using a stylus instrument and atomic force microscopy, and the surface roughness power spectra are calculated. The rubber viscoelastic modulus mastercurves are obtained from dynamic mechanical analysis measurements and the large-strain effective modulus is obtained from strain sweep data. The rubber friction is measured at different temperatures and sliding velocities, and is compared to the calculated data obtained using the Persson contact mechanics theory. We conclude that in addition to the viscoelastic deformations of the rubber surface by the road asperities, there is an important contribution to the rubber friction from shear processes in the area of contact. The analysis shows that the latter contribution may arise from rubber molecules (or patches of rubber) undergoing bonding-stretching-debonding cycles as discussed in a classic paper by Schallamach.

[Recruitment of Suitable Families to Identify Causative Genes in Hereditary Strabismus]. / Zur Rekrutierung geeigneter Familien für die Identifikation ursächlicher Gene des erblichen Strabismus.

PURPOSE: The cause and origin of primary strabismus are not well understood. It is thought that there is multifactorial genetic inheritance. Only linkage analysis has been applied to study the genetic causes and correlations. The objective of this study was the compilation and statistical evaluation of a useful cohort of families for linkage analysis. METHODS: The archives of the Department of Ophthalmology of the Justus-Liebig-University Gießen were used as a database for this study. Medical records of visits between January 2001 and July 2008 were analysed. Evaluation was based on the medical history form. The data set was scanned for index families in which at least two members had any form of primary strabismus. Patients were classified according to their type of primary strabismus. Families who were most suitable for linkage analysis were approached. A disease specific questionnaire was developed to complete the data. RESULTS: Between January 2001 and July 2008, 20,813 patients affected by primary strabismus were treated. The data set contained 2380 patients with a positive family history of primary strabismus. The majority presented with esotropia (67 %), followed by exotropia (21 %). In most cases (80 %), two family members were affected and the child-parent relationship contributed the largest group, including 948 cases (40 %). Affected siblings were found in 397 families (17 %). Three affected patients were identified in 432 (18 %) families. In these, the relationship parent-child-sibling occurred most frequently, with 143 cases (6 %). A positive family history of at least four related patients was found in 46 families (2 %). Forty-two families were particularly suitable for linkage analysis. Seventeen of the 42 families answered a questionnaire aimed at improving the data set. Three families finally participated in ophthalmic examinations and agreed to blood sampling to perform linkage analysis. CONCLUSION: The fraction of families with strabismus patients in more than two consecutive generations was extremely low. If these families are included in any study, this should be coupled to treatment to improve compliance.

Role of hydrophobicity on interfacial fluid flow: theory and some applications.

The fluid flow through a seal interface depends on the percolating non-contact channels morphology, size and length, and on the interfacial surface energies. In particular, hydrophobic interfaces may expel fluids and decrease the fluid flow of seals, while increasing the sliding friction. We present results of interfacial fluid flow experiments on a hydrostatic column device which demonstrate how interfacial hydrophobicity can block fluid flow at interfaces and reduce the leak rate of seals. The presented results may help to understand the role of interfacial hydrophobicity in many practical applications, some of which we discuss briefly in this paper, e.g., rubber wiper blades on hydrophobic (usually wax-coated) glass, the locomotion of insects on surfaces in water, and syringes.

[Specific gene therapy for hereditary retinal dystrophies - an update]. / Spezifische Gentherapie bei erblichen Netzhauterkrankungen - ein Update.

Treatment possibilities based on specific gene therapy strategies have become reality for a small number of patients with hereditary retinal dystrophies and are currently under investigation in several clinical trials worldwide. The most advanced studies are for patients suffering from mutations in the RPE65 gene. In addition, studies are ongoing for patients with disease causing mutations in the MERTK, REP1, ABCA4, or Myosin7A gene. Depending on the size of the gene copy to be transferred, two vectors are currently used in clinical trials: vectors based on adeno-associated virus (AAV) or on lentivirus (equine infectious anaemia virus, EIAV). An important aspect of current research includes the capacity to objectively measure the treatment effect in patients, since this is currently limited. This article gives an overview of the current state of specific gene therapy for hereditary retinal dystrophies.

Predictors of return to work in people with major depression: Results from a supported employment program in Germany.

BACKGROUND: Depression is a common mental disorder and is associated with work disability. For the implementation of evidence-based interventions, such as Individual Placement and Support (IPS) for people with depression in Germany, the aim of this study was to investigate client variables that predict return to work. METHODS: The sample consisted of 129 participants, initially treated in a psychiatric hospital due to major depression, who participated in IPS as part of a German clinical trial. Baseline demographic (age, sex, education, sickness absence days, employment status), psychiatric (symptom severity, comorbidity, general physical and mental health, disability), and neuropsychological (self-rated deficits, test performance) variables were included. Return to work within one year was predicted using separate and overall binary logistic regression analyses. RESULTS: A total of 70 participants (56 %) returned to work within the one-year follow-up period. >100 days of sick leave in the year prior to study entry (vs. <100 days) and higher self-rated cognitive deficits were significantly associated with reduced odds of return to work within one year of IPS. LIMITATIONS: The sample consisted of participants with a relatively good work history who were assigned to IPS by the treatment team, thus, the generalizability of the results is limited. CONCLUSIONS: People with depression who participate in IPS interventions might benefit from specifically targeting perceived cognitive deficits. Factors associated with prolonged sick leave due to depression and their role in return to work with IPS need further investigation.

Comparability of input parameters in the German Retina.net ROP registry and the EU-ROP registry - An exemplary comparison between 2011 and 2021.

PURPOSE: The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries. METHODS: Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments. RESULTS: The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021. CONCLUSION: Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021.

Positional cloning of the gene associated with X-linked juvenile retinoschisis.

X-linked juvenile retinoschisis(RS) is a recessively inherited vitreo-retinal degeneration characterized by macular pathology and intraretinal splitting of the retina. The RS gene has been localized to Xp22.2 to an approximately 1 Mb interval between DXS418 and DXS999/DXS7161. Mapping and expression analysis of expressed sequence tags have identified a novel transcript, designated XLRS1, within the centromeric RS locus that is exclusively expressed in retina. The predicted XLRS1 protein contains a highly conserved motif implicated in cell-cell interaction and thus may be active in cell adhesion processes during retinal development. Mutational analyses of XLRS1 in affected individuals from nine unrelated RS families revealed one nonsense, one frameshift, one splice acceptor and six missense mutations segregating with the disease phenotype in the respective families. These data provide strong evidence that the XLRS1 gene, when mutated, causes RS.

Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa. Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA. Disease genes implicated in other forms of arCSRD are expected to encode proteins present in the neuroretina or in the retinal pigment epithelium (RPE). The RPE, a monolayer of cells separating the vascular-rich choroid and the neuroretina, is in intimate contact with the outer segments of rods and cones via the microvilli surrounding the photoreceptors. The RPE expresses a tissue-specific and evolutionarily highly conserved 61 kD protein (RPE65) present at high levels in vivo. Although the function of RPE65 is not yet known, an important role in the RPE/photoreceptor vitamin-A cycle is suggested by the fact that RPE65 associates both with serum retinol-binding protein and with the RPE-specific 11-cis retinol dehydrogenase, an enzyme active in the synthesis of the visual pigment chromophore 11-cis retinal. Here we report that the analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation (Pro363Thr), two point mutations affecting splicing (912 + 1G-->T and 65 + 5G-->A) and two small re-arrangements (ins144T and 831del8) on a total of nine alleles of five patients with arCSRD. In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina.

Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis.

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.

An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness.

The locus for the incomplete form of X-linked congenital stationary night blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and DXS255. We identified a retina-specific calcium channel alpha1-subunit gene (CACNA1F) in this region, consisting of 48 exons encoding 1966 amino acids and showing high homology to L-type calcium channel alpha1-subunits. Mutation analysis in 13 families with CSNB2 revealed nine different mutations in 10 families, including three nonsense and one frameshift mutation. These data indicate that aberrations in a voltage-gated calcium channel, presumably causing a decrease in neurotransmitter release from photoreceptor presynaptic terminals, are a frequent cause of CSNB2.

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

[Work and Employment Situation of People with Mental Illness Receiving Independent Supported Housing: An Analysis of Routine Data from a Community Psychiatry Service]. / Die Arbeits- und Beschäftigungssituation von psychisch erkrankten Menschen mit ambulanter Wohnunterstützung: Eine Auswertung gemeindepsychiatrischer Routinedaten.

OBJECTIVES: Due to insufficient empirical data on the occupational participation of people affected by severe mental illness receiving integration assistance, routine data from a community psychiatry service were evaluated. METHODS: Reference workers filled out a short questionnaire on different occupational and employment aspects of their clients from supported housing/floating outreach. In addition to descriptive and exploratory analyses, overall results from previous survey rounds were also evaluated. RESULTS: N=1418 individuals (M=47.6 years) could be included, of whom approximately 45% had no job, sheltered employment, or daytime service. This percentage has remained almost unchanged over the last decades. CONCLUSION: Overall, there is an urgent need for action to improve occupational participation opportunities for people with mental illness and substance addiction.

Everyday memory in patients with depression: An explorative pilot study using an ecological assessment paradigm.

BACKGROUND: People with major depressive disorder (MDD) often experience significant memory problems in their daily lives, which, however, frequently do not correspond to standardized memory test (SMT) results. The present pilot study aimed to examine the everyday memory performance of people with MDD by means of an ecological assessment paradigm (EAP). METHODS: Participants were unexpectedly called one week after their neuropsychological test assessment and asked about their memories of specific details of the former test situation. Associations of this EAP with SMT, subjective everyday memory problems, and symptom coping were exploratively analyzed. RESULTS: The study involved 22 MDD inpatients (M = 42.5 years, 64% female) and 22 comparable healthy control persons. MDD patients showed a significantly reduced performance in the EAP as well as in the SMT and they reported more memory problems in their daily lives. However, the EAP was not related to SMT results assessed a week before. Moreover, only the EAP was significantly associated with subjective daily memory problems and (distraction) coping style in the MDD group. CONCLUSIONS: The EAP appears to better reflect the everyday memory problems of persons with depression than standardized test procedures. However, the findings need to be validated by further research with larger samples.