Explicitly encoding the cyclic nature of breathing signal allows for accurate breathing motion prediction in radiotherapy with minimal training data.

Background and purpose: Active breathing motion management in radiotherapy consists of motion monitoring, quantification and mitigation. It is impacted by associated latencies of a few 100 ms. Artificial neural networks can successfully predict breathing motion and eliminate latencies. However, they require usually a large dataset for training. The objective of this work was to demonstrate that explicitly encoding the cyclic nature of the breathing signal into the training data enables significant reduction of training datasets which can be obtained from healthy volunteers. Material and methods: Seventy surface scanner breathing signals from 25 healthy volunteers in anterior-posterior direction were used for training and validation (ratio 4:1) of long short-term memory models. The model performance was compared to a model using decomposition into phase, amplitude and a time-dependent baseline. Testing of the models was performed on 55 independent breathing signals in anterior-posterior direction from surface scanner (35 lung, 20 liver) of 30 patients with a mean breathing amplitude of (5.9 ± 6.7) mm. Results: Using the decomposed breathing signal allowed for a reduction of the absolute root-mean square error (RMSE) from 0.34 mm to 0.12 mm during validation. Testing using patient data yielded an average absolute RMSE of the breathing signal of (0.16 ± 0.11) mm with a prediction horizon of 500 ms. Conclusion: It was demonstrated that a motion prediction model can be trained with less than 100 datasets of healthy volunteers if breathing cycle parameters are considered. Applied to 55 patients, the model predicted breathing motion with a high accuracy.

Durvalumab impacts progression-free survival while high-dose radiation >66 Gy improves local control without excess toxicity in unresectable NSCLC stage III: Real-world data from the Austrian radio-oncological lung cancer study association registry (ALLSTAR).

BACKGROUND: Chemo-radioimmunotherapy with total radiation doses of 60-66 Gy in 2 Gy fractions is the standard of care for non-small cell lung cancer (NSCLC) UICC stage III. The Austrian radio-oncological lung cancer study association registry (ALLSTAR) is a prospective multicentre registry intended to document clinical practice at the beginning of the Durvalumab era. PATIENTS AND METHODS: Patients were eligible if they had pathologically verified unresectable NSCLC stage III with a curative treatment option. Chemo-radiation combined with immunotherapy was performed according to local treatment practices. The endpoints were local control (LC), progression-free survival (PFS) and toxicity. RESULTS: Between 2020/03 and 2023/04, 12/14 (86 %) Austrian radiation-oncology centres recruited 188 patients (median 17, range: 1-89). PD-L1 testing was performed in 173/188 (93 %) patients. The median interval between the end of chemoradiotherapy and start of Durvalumab was 14 days (range: 1-65). About 40 % (75/188) of the patients received a total radiation dose of > 66 Gy (range: 67.1-100), which improved 2-year LC (86 % versus 60 %, HR = 0.41; 95 %-CI: 0.17-0.98; log-rank p-value < 0.05). Median PFS for patients with Durvalumab was 25.8 months (95 %-CI: 21.9-not reached) compared to 15.7 months (95 %-CI: 13.2-27.8) for those without (HR = 1.88; 95 %-CI: 1.16-3.05; log-rank p-value < 0.01). The rates of esophageal and pulmonary toxicities were 34.6 % and 23.9 %, respectively, including one case of grade 4 pneumonitis. In the subcohort of 75 patients who received > 66 Gy, 19 (25 %) cases of pulmonary toxicity grades 1-3 were observed. CONCLUSION: While Durvalumab impacts PFS, LC can be improved by total radiation doses > 66 Gy without excess toxicity.

Clinical Implementation and Evaluation of Auto-Segmentation Tools for Multi-Site Contouring in Radiotherapy.

Background and purpose: Tools for auto-segmentation in radiotherapy are widely available, but guidelines for clinical implementation are missing. The goal was to develop a workflow for performance evaluation of three commercial auto-segmentation tools to select one candidate for clinical implementation. Materials and Methods: One hundred patients with six treatment sites (brain, head-and-neck, thorax, abdomen, and pelvis) were included. Three sets of AI-based contours for organs-at-risk (OAR) generated by three software tools and manually drawn expert contours were blindly rated for contouring accuracy. The dice similarity coefficient (DSC), the Hausdorff distance, and a dose/volume evaluation based on the recalculation of the original treatment plan were assessed. Statistically significant differences were tested using the Kruskal-Wallis test and the post-hoc Dunn Test with Bonferroni correction. Results: The mean DSC scores compared to expert contours for all OARs combined were 0.80 ± 0.10, 0.75 ± 0.10, and 0.74 ± 0.11 for the three software tools. Physicians' rating identified equivalent or superior performance of some AI-based contours in head (eye, lens, optic nerve, brain, chiasm), thorax (e.g., heart and lungs), and pelvis and abdomen (e.g., kidney, femoral head) compared to manual contours. For some OARs, the AI models provided results requiring only minor corrections. Bowel-bag and stomach were not fit for direct use. During the interdisciplinary discussion, the physicians' rating was considered the most relevant. Conclusion: A comprehensive method for evaluation and clinical implementation of commercially available auto-segmentation software was developed. The in-depth analysis yielded clear instructions for clinical use within the radiotherapy department.

Characterising Biosecurity Initiatives Globally to Support the Development of a Progressive Management Pathway for Terrestrial Animals: A Scoping Review.

While biosecurity is of increasing importance globally, there is still limited evidence of the factors or elements that support the progressive and sustainable scaling up of biosecurity along the value chains from the local to the global level. To gain insight into the current body of literature on biosecurity, a mixed-methods approach was used based on a scoping literature review and an online survey with subject matter experts. Six databases were searched for published literature, and textual information from titles and abstracts of all included records (n = 266) were analysed through inductive content analysis to build biosecurity-relevant categories and identify strengths, weaknesses, opportunities, and threats (SWOT) of existing biosecurity systems or initiatives (such as projects or programs). Most records focused on initiatives in high-income countries, traditional livestock species (pigs, poultry, and large ruminants), and the production stage and had a disease-specific focus. No records described a comprehensive or global framework to progressively scale up biosecurity. Overall, the findings highlight the need for initiatives such as the FAO Progressive Management Pathway for Terrestrial Animal Biosecurity (FAO-PMP-TAB), which is a stepwise approach for strengthening biosecurity management along value chains to enhance the health, resilience, and sustainability of animal sectors. The findings highlight important elements and provide recommendations useful for developing approaches or a global framework to progressively improve biosecurity management.

Strain-inducing photochemical chlorination of graphene nanoribbons on SiC (0001).

As different low-dimensional materials are sought to be incorporated into microelectronic devices, graphene integration is dependent on the development of band gap opening strategies. Amidst the different methods currently investigated, application of strain and use of electronic quantum confinement have shown promising results. In the present work, epitaxial graphene nanoribbons (GNR), formed by surface graphitization of SiC (0001) on crystalline step edges, were submitted to photochemical chlorination. The incorporation of Cl into the buffer layer underlying graphene increased the compressive uniaxial strain in the ribbons. Such method is a promising tool for tuning the band gap of GNRs.

African Swine Fever in Mongolia: Course of the Epidemic and Applied Control Measures.

African swine fever (ASF) is spreading rapidly in Asia and was confirmed in Mongolia on 10 January 2019. Following the outbreak confirmation, a state emergency committee was established with representation from municipal authorities and other relevant authorities including the General Authority for Veterinary Services, National Emergency Management Agency, General Agency for Specialized Inspection, and the Ministry of Environment and Tourism. The committee provided recommendations and coordinated closely with the State Central Veterinary Laboratory to ensure quick outbreak investigation and response. In addition to outbreak investigations, sampling took place at farms and food premises and suggests a link between the outbreaks and swill feeding practices among backyard pig farmers. Upon government request, the Food and Agriculture Organization of the United Nations (FAO) deployed an expert team to assist in identifying risk factors for the disease spread and provide recommendations as how to improve disease prevention and response. Following the control measures from the involved agencies, the epidemic was successfully controlled and declared over on 11 April 2019. In total, the epidemic affected 83 pig farming households and led to a total of 2862 dead or culled pigs in eleven districts of seven provinces in Mongolia.

Influence of Proximity to Supporting Substrate on van der Waals Epitaxy of Atomically Thin Graphene/Hexagonal Boron Nitride Heterostructures.

Combining graphene and the insulating hexagonal boron nitride (h-BN) into two-dimensional heterostructures is promising for novel, atomically thin electronic nanodevices. A heteroepitaxial growth, in which these materials are grown on top of each other, will be crucial for their scalable device integration. However, during this so-called van der Waals epitaxy, not only the atomically thin substrate itself must be considered but also the influences from the supporting substrate below it. Here, we report not only a substantial difference between the formation of h-BN on single- (SLG) and on bi-layer epitaxial graphene (BLG) on SiC, but also vice versa, that the van der Waals epitaxy of h-BN at growth temperatures well below 1000 °C affects the varying number of graphene layers differently. Our results clearly demonstrate that the additional graphene layer in BLG enhances the distance to the corrugated, carbon-rich interface of the supporting SiC substrate and thereby diminishes its influence on the van der Waals epitaxy, leading to a homogeneous formation of a smooth, atomically thin heterostructure, which will be required for a scalable device integration of 2D heterostructures.

A Competency Framework for Developing Global Laboratory Leaders.

Building sustainable national health laboratory systems requires laboratory leaders who can address complex and changing demands for services and build strong collaborative networks. Global consensus on laboratory leadership competencies is critically important to ensure the harmonization of learning approaches for curriculum development across relevant health sectors. The World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), the European Centre for Disease Prevention and Control (ECDC), the U.S. Centers for Disease Control and Prevention (CDC), and the Association of Public Health Laboratories (APHL) have partnered to develop a Laboratory Leadership Competency Framework (CF) that provides a foundation for the Global Laboratory Leadership Programme (GLLP). The CF represents the first global consensus from multiple disciplines on laboratory leadership competencies and provides structure for the development of laboratory leaders with the knowledge, skills and abilities to build bridges, enhance communication, foster collaboration and develop an understanding of existing synergies between the human, animal, environmental, and other relevant health sectors.

Inflatable multichannel rectal applicator for adaptive image-guided endoluminal high-dose-rate rectal brachytherapy: design, dosimetric characteristics, and first clinical experiences.

PURPOSE: To investigate the dosimetric results and first clinical experiences with a new designed balloon applicator with adjustable catheters for endoluminal brachytherapy for patients with locally advanced rectal cancer not undergoing surgery. MATERIAL AND METHODS: The applicator consists of an inflatable rectal balloon with six attached Foley catheters used as guidance for the inserted brachytherapy plastic needles. The construction of the applicator and the dosimetric profile in terms of representative dose points in 0, 2, 5, 10 mm ipsilaterally and in 0 mm contralaterally are described. The first clinical outcomes in three patients are reported. RESULTS: For all three patients, a reproducible dose gradient was achieved. The surface dose on the target side was 204 ± 19% of the normalized dose in 5 mm (100%) tissue depth, and 143 ± 8% in 2 mm and 64 ± 3% in 10 mm tissue depth, while the surface dose on the contra-lateral side was 20 ± 8%. After radiochemotherapy with 50 Gy external beam radiotherapy and concomitant administration of capecitabine, a HDR brachytherapy boost in 2-3 fractions of 7-10 Gy each was delivered. All patients achieved a clinical complete response 3 month after the treatment, and no major toxicity was observed. CONCLUSION: The use of the applicator was clinically feasible, and resulted in a stable and reproducible dose distribution. First clinical results are promising.

The impact of insecticide-treated material to reduce flies among pork outlets in Kampala, Uganda.

Synanthropic flies have adapted to the mass of decaying organic matter near human settlements. As such, they feed and breed on food, faeces and other organic material and are known vectors for various diseases. Many of these diseases are associated with food, and foodborne diseases are of growing concern in developing countries where human population and food consumption increase. This pilot study aims at investigating the impact of a novel application of insecticide-treated material (ZeroFly®) to reduce flies among pork outlets in Kampala, Uganda. A cross-sectional survey randomly selected 60 of 179 pork outlets in Kampala. A controlled longitudinal trial followed in which 23 out of the 60 pork outlets were recruited for an intervention with insecticide-treated material. The pork outlets were randomly allocated to a group of 18 netted pork outlets (intervention) and five non-netted pork outlets (control). Monitoring took place over 15 weeks including 2 weeks as the baseline survey. The units were monitored for fly abundance using non-attractant sticky traps, which were placed within the pork outlet once per week for 48 consecutive hours. Medians of fly numbers before and after the intervention indicated a decrease of fly numbers of 48% (p = 0.002). Fly bioassays showed that the insecticidal activity of the netting remained active over the entire intervention period and led to a total paralysis of flies within at least 6 h after exposure. Insecticide-treated material provides a practical and sustainable solution in controlling flies and is therefore recommended as a complementary strategy for an integrated vector control and hygiene management.

HLA-Bw4 80(T) and multiple HLA-Bw4 copies combined with KIR3DL1 associate with spontaneous clearance of HCV infection in people who inject drugs.

BACKGROUND & AIMS: Natural killer (NK) cell function is regulated by inhibitory and activating receptors including killer cell immunoglobulin-like receptors (KIRs). Here, we analyzed the impact of different KIR/KIR-ligand genotypes on the outcome of hepatitis C virus (HCV) infection in people who inject drugs (PWID). METHODS: KIR/KIR-ligand genotypes associated with spontaneous clearance of HCV infection were identified in a cohort of PWID from Germany (n=266) and further validated in a second anti-HCV positive cohort of PWID recruited in North America (n=342). NK cells of PWID and healthy donors were functionally characterized according to their KIR/KIR-ligand genotype by flow cytometry. RESULTS: Multivariate logistic regression analysis revealed that KIR3DL1/HLA-Bw4 80(T) was associated with spontaneous clearance of HCV infection in PWID, which was confirmed in the PWID cohort from North America. Compared with PWID with detectable HCV RNA, the frequency of individuals with multiple HLA-Bw4 alleles was significantly higher in anti-HCV positive PWID with resolved HCV infection (29.7% vs. 15.2%; p=0.0229) and in anti-HCV seronegative PWID (39.2%; p=0.0006). KIR3DL1+ NK cells from HLA-Bw4 80(T)-positive PWID showed superior functionality compared to HLA-Bw4 80(I)-positive PWID. This differential impact was not observed in healthy donors; however, the HLA-Bw4 copy number strongly correlated with the functionality of KIR3DL1+ NK cells. CONCLUSIONS: HLA-Bw4-80(T) and multiple HLA-Bw4 copies in combination with KIR3DL1 are associated with protection against chronic hepatitis C in PWID by distinct mechanisms. Better licensing of KIR3DL1+ NK cells in the presence of multiple HLA-Bw4 copies is beneficial prior to seroconversion whereas HLA-Bw4 80(T) may be beneficial during acute hepatitis C. Lay summary: Natural killer (NK) cells are part of the innate immune system and are regulated by a complex network of activating and inhibiting receptors. The regulating receptor-ligand pairs of an individual are genetically determined. Here, we identified a particular set of ligand and receptor genes that are associated with better functionality of NK cells and better outcome upon exposure to HCV in a high-risk group.

Efficient Nitrogen Doping of Single-Layer Graphene Accompanied by Negligible Defect Generation for Integration into Hybrid Semiconductor Heterostructures.

While doping enables application-specific tailoring of graphene properties, it can also produce high defect densities that degrade the beneficial features. In this work, we report efficient nitrogen doping of ∼11 atom % without virtually inducing new structural defects in the initial, large-area, low defect, and transferred single-layer graphene. To shed light on this remarkable high-doping-low-disorder relationship, a unique experimental strategy consisting of analyzing the changes in doping, strain, and defect density after each important step during the doping procedure was employed. Complementary micro-Raman mapping, X-ray photoelectron spectroscopy, and optical microscopy revealed that effective cleaning of the graphene surface assists efficient nitrogen incorporation accompanied by mild compressive strain resulting in negligible defect formation in the doped graphene lattice. These original results are achieved by separating the growth of graphene from its doping. Moreover, the high doping level occurred simultaneously with the epitaxial growth of n-GaN micro- and nanorods on top of graphene, leading to the flow of higher currents through the graphene/n-GaN rod interface. Our approach can be extended toward integrating graphene into other technologically relevant hybrid semiconductor heterostructures and obtaining an ohmic contact at their interfaces by adjusting the doping level in graphene.

Review of Participatory Epidemiology Practices in Animal Health (1980-2015) and Future Practice Directions.

In this study we combined an inventory of the major applications, geographic regions and diseases covered by participatory epidemiology (PE) activities in the field of animal health since 1980, together with an email discussion forum with PE practitioners from different regions of the world. The inventory included the search of peer-reviewed papers, master and technical reports, conference proceedings, manuals, training materials and projects. The search resulted in a low number of PE activity results until the year 2000, followed by a considerable increase (especially from 2012). Most of the identified activities were implemented in Africa and Asia, and focused on surveillance, disease survey and prioritization, and disease control. Seventy-nine PE practitioners working predominantly in Africa, Asia and Europe (29, 22 and 18 respectively) contributed to the email discussion forum. They proposed various modifications to the existing PE definition and discussed different issues related to the applicatoin of PE, its institutionalization for use in policy development, as well as the priorities for future development. The need to increase the number of PE trained people together with some methodological developments and the application of this methodology in developed countries, were some of the points highlighted during the forum. These factors stress the importance of further developing PE as a useful approach for engaging communities in addressing animal and related public health risks.

Nanoscale Characterization of Carrier Dynamic and Surface Passivation in InGaN/GaN Multiple Quantum Wells on GaN Nanorods.

Using advanced two-photon excitation confocal microscopy, associated with time-resolved spectroscopy, we characterize InGaN/GaN multiple quantum wells on nanorod heterostructures and demonstrate the passivation effect of a KOH treatment. High-quality InGaN/GaN nanorods were fabricated using nanosphere lithography as a candidate material for light-emitting diode devices. The depth- and time-resolved characterization at the nanoscale provides detailed carrier dynamic analysis helpful for understanding the optical properties. The nanoscale spatially resolved images of InGaN quantum well and defects were acquired simultaneously. We demonstrate that nanorod etching improves light extraction efficiency, and a proper KOH treatment has been found to reduce the surface defects efficiently and enhance the luminescence. The optical characterization techniques provide depth-resolved and time-resolved carrier dynamics with nanoscale spatially resolved mapping, which is crucial for a comprehensive and thorough understanding of nanostructured materials and provides novel insight into the improvement of materials fabrication and applications.

Vertically Oriented Growth of GaN Nanorods on Si Using Graphene as an Atomically Thin Buffer Layer.

The monolithic integration of wurtzite GaN on Si via metal-organic vapor phase epitaxy is strongly hampered by lattice and thermal mismatch as well as meltback etching. This study presents single-layer graphene as an atomically thin buffer layer for c-axis-oriented growth of vertically aligned GaN nanorods mediated by nanometer-sized AlGaN nucleation islands. Nanostructures of similar morphology are demonstrated on graphene-covered Si(111) as well as Si(100). High crystal and optical quality of the nanorods are evidenced through scanning transmission electron microscopy, micro-Raman, and cathodoluminescence measurements supported by finite-difference time-domain simulations. Current-voltage characteristics revealed high vertical conduction of the as-grown GaN nanorods through the Si substrates. These findings are substantial to advance the integration of GaN-based devices on any substrates of choice that sustains the GaN growth temperatures, thereby permitting novel designs of GaN-based heterojunction device concepts.

Use of disulfiram for alcohol relapse prevention in patients in opioid maintenance treatment.

OBJECTIVES: The aim of this study was to assess the effectiveness, tolerability, and safety of alcohol relapse prevention with disulfiram in alcohol-dependent patients in opioid maintenance treatment under routine treatment conditions. METHODS: Twenty-nine opioid maintenance treatment patients were observed from the beginning of outpatient disulfiram treatment for up to 6 months. Patients received disulfiram (mostly 300 mg/d) together with their daily opioid dose. Patients were assessed through urine screens for alcohol (ethyl gluconoride) and other drugs at least twice monthly; blood chemistry analyses after 1, 3, and 6 months; and clinical interviews after 3 and 6 months. RESULTS: Most patients presented with somatic and/or psychiatric comorbidity and/or polydrug use at baseline. Half of the patients completed 6 months of disulfiram treatment. Alcohol use was low during disulfiram treatment. Levels of other drug use did not change. For most patients, 1 or more adverse events were reported, often mild and/or short lived. Three patients experienced severe adverse events attributable to disulfiram. CONCLUSIONS: Disulfiram is a viable treatment option for the high-risk population studied here. A close monitoring of side effects and adverse events is necessary, in particular, in patients with polysubstance use.

Disentangling the effects of nanoscale structural variations on the light emission wavelength of single nano-emitters: InGaN/GaN multiquantum well nano-LEDs for a case study.

The scattering in the light emission wavelength of semiconductor nano-emitters assigned to nanoscale variations in strain, thickness, and composition is critical in current and novel nanotechnologies from highly efficient light sources to photovoltaics. Here, we present a correlated experimental and theoretical study of single nanorod light emitting diodes (nano-LEDs) based on InGaN/GaN multiquantum wells to separate the contributions of these intrinsic fluctuations. Cathodoluminescence measurements show that nano-LEDs with identical strain states probed by non-resonant micro-Raman spectroscopy can radiate light at different wavelengths. The deviations in the measured optical transitions agree very well with band profile calculations for quantum well thicknesses of 2.07-2.72 nm and In fractions of 17.5-19.5% tightly enclosing the growth values. The nanorod surface roughness controls the appearance of surface optical phonon modes with direct implications on the design of phonon assisted nano-LED devices. This work establishes a new, simple, and powerful methodology for fundamental understanding as well as quantitative analysis of the strain - light emission relationship and surface-related phenomena in the emerging field of nano-emitters.

Longitudinal patterns of benzodiazepine consumption in a German cohort of methadone maintenance treatment patients.

OBJECTIVE: Cross-sectional studies show that considerable proportions of opiate dependents in methadone maintenance treatment (MMT) consume benzodiazepines (BZD). The longitudinal patterns of BZD use over time were described here. METHODS: After admission to MMT, patients from two outpatient MMT clinics (n = 345) were observed for up to 2 years whilst in treatment. The use of BZD, cannabis, opiates and cocaine was assessed by urine sampling carried out twice a month. RESULTS: For the whole sample, the mean BZD-positive urine specimen rate was 0.36 during the first 3 months. Rates slightly decreased during the first year and remained stable afterwards (last observation carried forward). For study completers (n = 152), the rate decreased over time, from 0.31 (first 3-month period) to 0.19 (last period; p < 0.001). According to a longitudinal cluster analysis, 26% of all patients showed a pattern of constantly high BZD-positivity rates, mostly in combination with other substances. Inpatient detoxifications from BZD (carried out in 18% of cases) did not have a sustained effect on levels of BZD use. CONCLUSIONS: BZD consumption in MMT is often part of a polydrug consumption pattern and is associated with poorer treatment retention. It is necessary to further investigate the reasons for BZD use in MMT patients and to develop effective interventions to reduce levels of BZD consumption.