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Abstract Tinea capitis is a prevalent dermatophyte infection among German children, primarily caused by Microsporum canis, Trichophyton mentagrophytes and Trichophyton benhamiae. Other pathogens, such as T. soudanense and M. audouinii, have also been identified in Germany. This case report describes a 10‐year‐old Angolan girl with chronic osteomyelitis who was brought to Germany for treatment, which was organized by the Friedensdorf International (Peacevillage International). In addition to chronic osteomyelitis of the lower leg, the patient presented with alopecic areas of the scalp with adherent scales, which raised the suspicion of tinea capitis. Fungal cultivation and polymerase chain reaction (PCR) diagnostics revealed a coinfection of T. soudanense and M. audouinii, which, to the best of our knowledge, has not been previously reported in Europe. After 4 weeks of systemic terbinafine treatment and topical use of ciclopirox solution and clotrimazole cream, there was a marked improvement in the patient's condition. This was confirmed by a negative fungal culture and PCR; no adverse events were reported. This report highlights a rare dual dermatophyte infection caused by T. soudanense and M. audouinii in Europe, and the successful response to treatment with systemic terbinafine and topical ciclopirox solution as well as clotrimazole cream.

Abstract Objective This study aimed to (1) characterise sleep disturbances and emotional/behavioural difficulties among healthy German children and adolescents aged 3 to 13 years, (2) examine the association between parent-reported sleep problems and emotional/behavioural difficulties, (3) point out possible relations between specific kinds of sleep disturbances and different behavioural difficulties. Methods Data were collected between 2011 and 2015 within the LIFE Child study in Germany. The sample included 1101 3- to 13-year-old children and adolescents. Information on sleep disturbances—assessed via the Children’s Sleep Habits Questionnaire (CSHQ), emotional/behavioural difficulties—assessed via the Strengths and Difficulties Questionnaire (SDQ), and socioeconomic status was provided by participants’ parents. Multiple regressions were applied to analyse the associations between general and specific sleep disturbances (independent variables) and emotional/behavioural difficulties (dependent variables). Results The total CSHQ score was positively associated with the total SDQ score and all SDQ subscales (emotional problems, conduct problems, hyperactivity/inattention, peer relationship problems). Most of the CSHQ subscales were related to SDQ subscale scores, except for a few non-significant relations with hyperactivity/inattention and conduct problems. The CSHQ total score, daytime sleepiness, sleep duration and parasomnias showed the strongest associations with the SDQ total score. Conclusion This study confirms an association between children’s and adolescents’ sleep habits and psychological health. We were able to demonstrate the association between sleep problems and emotional/behavioural difficulties in a large sample of healthy participants. In particular, we observed a significant relation between parasomnias and hyperactive/inattentive behaviour as well as a significant association between emotional problems and sleep problems, especially daytime sleepiness, sleep anxiety and parasomnias.

Purpose: This work evaluates an online adaptive (OA) workflow for head-and-neck (H&N) intensity-modulated proton therapy (IMPT) and compares it with full offline replanning (FOR) in patients with large anatomical changes. Methods: IMPT treatment plans are created retrospectively for a cohort of eight H&N cancer patients that previously required replanning during the course of treatment due to large anatomical changes. Daily cone-beam CTs (CBCT) are acquired and corrected for scatter, resulting in 253 analyzed fractions. To simulate the FOR workflow, nominal plans are created on the planning-CT and delivered until a repeated-CT is acquired; at this point, a new plan is created on the repeated-CT. To simulate the OA workflow, nominal plans are created on the planning-CT and adapted at each fraction using a simple beamlet weight-tuning technique. Dose distributions are calculated on the CBCTs with Monte Carlo for both delivery methods. The total treatment dose is accumulated on the planning-CT. Results: Daily OA improved target coverage compared to FOR despite using smaller target margins. In the high-risk CTV, the median D98 degradation was 1.1 % and 2.1 % for OA and FOR, respectively. In the low-risk CTV, the same metrics yield 1.3 % and 5.2 % for OA and FOR, respectively. Smaller setup margins of OA reduced the dose to all OARs, which was most relevant for the parotid glands. Conclusion: Daily OA can maintain prescription doses and constraints over the course of fractionated treatment, even in cases of large anatomical changes, reducing the necessity for manual replanning in H&N IMPT.

With the availability of MRI linacs, online adaptive intensity modulated radiotherapy (IMRT) has become a treatment option for liver cancer patients, often combined with hypofractionation. Intensity modulated proton therapy (IMPT) has the potential to reduce the dose to healthy tissue, but it is particularly sensitive to changes in the beam path and might therefore benefit from online adaptation. This study compares the normal tissue complication probabilities (NTCPs) for liver and duodenal toxicity for adaptive and non-adaptive IMRT and IMPT treatments of liver cancer patients. Adaptive and non-adaptive IMRT and IMPT plans were optimized to 50 Gy (RBE = 1.1 for IMPT) in five fractions for 10 liver cancer patients, using the original MRI linac images and physician-drawn structures. Three liver NTCP models were used to predict radiation-induced liver disease, an increase in albumin-bilirubin level, and a Child–Pugh score increase of more than 2. Additionally, three duodenal NTCP models were used to predict gastric bleeding, gastrointestinal (GI) toxicity with grades >3, and duodenal toxicity grades 2–4. NTCPs were calculated for adaptive and non-adaptive IMRT and IMPT treatments. In general, IMRT showed higher NTCP values than IMPT and the differences were often significant. However, the differences between adaptive and non-adaptive treatment schemes were not significant, indicating that the NTCP benefit of adaptive treatment regimens is expected to be smaller than the expected difference between IMRT and IMPT.

Abstract Photon detection at microwave frequency is of great interest due to its application in quantum computation information science and technology. Herein are results from studying microwave response in a topological superconducting quantum interference device (SQUID) realized in Dirac semimetal Cd3As2. The temperature dependence and microwave power dependence of the SQUID junction resistance are studied, from which we obtain an effective temperature at each microwave power level. It is observed the effective temperature increases with the microwave power. This observation of large microwave response may pave the way for single photon detection at the microwave frequency in topological quantum materials.

ABSTRACT: Since the launch of the Strategic Partnership in 1999, the European Union and Latin America and the Caribbean countries have formed a political agenda for bi-regional dialogues. In this study we present a comprehensive analysis of the political and the technical levels of the bi-regional cooperation. The analytical approach that we develop to study bi-regional STI relations is based on a thorough examination of the legal foundations of the EU, which allows for assessment of the possibilities and limits. We identify the LAC dimension of the EU’s scientific policies, offering an overview of the challenges and achievements of bi-regional STI cooperation. These are derived from an analysis of limitations in the current cooperation programs. Additionally, the latter is being connected to the discussion of support needs that are raised by the survey participants. We provide a list of suggestions for further instruments and activities, as the main motive is to strengthen and widen the cooperation with concrete actions.

BackgroundFor many drugs, mechanisms of action with regard to desired effects and/or unwanted side effects are only incompletely understood. To investigate possible pleiotropic effects and respective molecular mechanisms, we describe here a catalogue of commonly used drugs and their impact on the blood transcriptome.Methods and resultsFrom a population-based cohort in Germany (LIFE-Adult), we collected genome-wide gene-expression data in whole blood using in Illumina HT12v4 micro-arrays (n = 3,378; 19,974 gene expression probes per individual). Expression profiles were correlated with the intake of active substances as assessed by participants' medication. This resulted in a catalogue of fourteen substances that were identified as associated with differential gene expression for a total of 534 genes. As an independent replication cohort, an observational study of patients with suspected or confirmed stable coronary artery disease (CAD) or myocardial infarction (LIFE-Heart, n = 3,008, 19,966 gene expression probes per individual) was employed. Notably, we were able to replicate differential gene expression for three active substances affecting 80 genes in peripheral blood mononuclear cells (carvedilol: 25; prednisolone: 17; timolol: 38). Additionally, using gene ontology enrichment analysis, we demonstrated for timolol a significant enrichment in 23 pathways, 19 of them including either GPER1 or PDE4B. In the case of carvedilol, we showed that, beside genes with well-established association with hypertension (GPER1, PDE4B and TNFAIP3), the drug also affects genes that are only indirectly linked to hypertension due to their effects on artery walls or their role in lipid biosynthesis.ConclusionsOur developed catalogue of blood gene expressions profiles affected by medication can be used to support both, drug repurposing and the identification of possible off-target effects.

Abstract Ciclopirox 8% hydroxypropyl chitosan (HPCH) [Marketed in different countries as the following registered (®) brands: Ciclopoli, Fulcare, Kitonail, Myconail, Niogermos, Niogermox, Onytec, Ony-Tec, Polinail, Privex, Rejuvenail] is the first topical nail lacquer developed using innovative drug formulation technology. It is indicated for the treatment of mild-to-moderate fungal infections of the nails that are caused by dermatophytes and/or other ciclopirox-sensitive fungi, without nail matrix involvement. HPCH is a patented drug formulation technology for the delivery of active principles into the nails based on a hydrosoluble semisynthetic amino-polysaccharide biopolymer derivative of chitosan. The lacquer acts as a protective barrier against microbiological attack, physical damage and/or aggressive chemicals. Results from in vitro studies suggest that the application of ciclopirox 8% HPCH nail lacquer improves drug permeation into and/or drug penetration through the nail, relative to the water-insoluble ciclopirox 8%, amorolfine 5% and efinaconazole 10% reference lacquers. In addition, in vitro and clinical studies in healthy subjects found that the concentration of ciclopirox reached in subungual fluids after application of ciclopirox 8% HPCH was sufficient for inhibiting fungal growth. In clinical studies in patients with mild-to-moderate onychomycosis, ciclopirox 8% HPCH was found to be more effective than the commercial water-insoluble ciclopirox 8% and amorolfine 5% lacquers, as indicated by higher complete cure, response and mycological cure rates at 48 weeks after treatment initiation. Ciclopirox 8% HPCH has been found to be generally well tolerated, with no treatment-related adverse events reported in patients using this nail lacquer. Thus, current evidence indicates that ciclopirox 8% HPCH represents a valuable treatment option for the treatment of patients with onychomycosis.

In recent decades, the use of psychosocial and psychiatric care systems has increased worldwide. A recent article proposed the concept of psychiatrization as an explanatory framework, describing multiple processes responsible for the spread of psychiatric concepts and forms of treatment. This article aims to explore the potentials of the Open Dialogue (OD) approach for engaging in less psychiatrizing forms of psychosocial support. While OD may not be an all-encompassing solution to de-psychiatrization, this paper refers to previous research showing that OD has the potential to 1) limit the use of neuroleptics, 2), reduce the incidences of mental health problems and 3) decrease the use of psychiatric services. It substantiates these potentials to de-psychiatrize psychosocial support by exploring the OD’s internal logic, its use of language, its processes of meaning-making, its notion of professionalism, its promotion of dialogue and how OD is set up structurally. The conclusion touches upon the dangers of co-optation, formalization and universalization of the OD approach and stresses the need for more societal, layperson competencies in dealing with psychosocial crises.

Purpose: To evaluate the suitability of low-dose CT protocols for online plan adaptation of head-and-neck patients. Methods: We acquired CT scans of a head phantom with protocols corresponding to CT dose index volume CTDIvol in the range of 4.2–165.9 mGy. The highest value corresponds to the standard protocol used for CT simulations of 10 head-and-neck patients included in the study. The minimum value corresponds to the lowest achievable tube current of the GE Discovery RT scanner used for the study. For each patient and each low-dose protocol, the noise relative to the standard protocol, derived from phantom images, was applied to a virtual CT (vCT). The vCT was obtained from a daily CBCT scan corresponding to the fraction with the largest anatomical changes. We ran an established adaptive workflow twice for each low-dose protocol using a high-quality daily vCT and the corresponding low-dose synthetic vCT. For a relative comparison of the adaptation efficacy, two adapted plans were recalculated in the high-quality vCT and evaluated with the contours obtained through deformable registration of the planning CT. We also evaluated the accuracy of dose calculation in low-dose CT volumes using the standard CT protocol as reference. Results: The maximum differences in D98 between low-dose protocols and the standard protocol for the high-risk and low-risk CTV were found to be 0.6% and 0.3%, respectively. The difference in OAR sparing was up to 3%. The Dice similarity coefficient between propagated contours obtained with low-dose and standard protocols was above 0.982. The mean 2%/2 mm gamma pass rate for the lowest-dose image, using the standard protocol as reference, was found to be 99.99%. Conclusion: The differences between low-dose protocols and the standard scanning protocol were marginal. Thus, low-dose CT protocols are suitable for online adaptive proton therapy of head-and-neck cancers. As such, considering scanning protocols used in our clinic, the imaging dose associated with online adaption of head-and-neck cancers treated with protons can be reduced by a factor of 40.