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Introduction Intratympanic corticosteroids are commonly used in the treatment of Menière’s disease (MD). However, few and small randomised controlled trials (RCT) on the effectiveness of intratympanic corticosteroids have been performed. A recent Cochrane review suggested that a well-conducted placebo-controlled RCT with a large study population is required to evaluate the effectiveness of the use of intratympanic corticosteroids in MD. The following protocol describes a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial to compare the effectiveness of methylprednisolone (62.5 mg/mL) to a placebo (sodium chloride 0.9%).Methods and analysis We aim to recruit 148 patients with unilateral MD from six hospitals in the Netherlands. Patients will be randomly assigned to either the methylprednisolone or the placebo group. Two injections will be given, one at baseline and one after 2 weeks. Follow-up assessments will be done at 3, 6, 9 and 12 months. The primary outcome will be the frequency of vertigo attacks. Attacks will be evaluated daily with the DizzyQuest app. Secondary outcomes include hearing loss, tinnitus, health-related quality of life, use of co-interventions and escape medication, (serious) adverse events and cost-effectiveness. These will be evaluated with audiometry and multiple commonly used, validated questionnaires. For the primary and secondary outcomes mixed model analysis, generalised estimating equation analysis and logistic regression analysis will be used.Ethics and dissemination This study was submitted via the Clinical Trials Information System, reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft and the local institutional review board of each participating centre. All data will be presented ensuring the integrity and anonymity of patients. Results will be published in scientific journals and presented on (inter)national conferences.Trial registration number This study is registered at ClinicalTrials.gov Protocol Registration and Results System, with the registration ID: NCT05851508.

RTKLIB which is an open source Global Navigation Satellite Systems (GNSS) software has gained rapid acceptance among Surveying professionals thanks to recent developments in UAS (Unmanned Aerial System) technology. RTKLIB enables standard and precise point positioning (PPP) in real-time and post-processing modes to be performed. As such, UAS users utilize this software to analyze GNSS data collected by GNSS systems on UAS. By being versatile and free, RTKLIB is commonly used by many; however, it is not the only freely available GNSS software. There are also freely available online GNSS data processing software running on servers. These online GNSS data processing services provide data processing in static, kinematic and rapid static modes. Because UAS collect data in kinematic mode, in this study, kinematic data processing by aforementioned software (CSRS-PPP, GAPS and APPS) is analyzed. The results coming from these software are compared against the results produced by photogrammetric software (Agisoft Metashape and Pix4Dmapper). The aim of this practical project is to produce generalizable knowledge about the performance of these software. It is found out that RTKLIB and CSRS-PPP achieved cm-level precision. Yet, GAPS and APPS achieved dm-level precision both for horizontal and vertical coordinates. This study demonstrates the precision and accuracy expected from these software if they are used for kinematic GNSS data processing.

In this study, a hydrographic map of a South Florida canal is prepared using RTK GPS (Real Time Kinematic Global Positioning System) measurements combined with a hydrolite (single beam echo sounder). RTK GPS measurements are made using both single RTK and Network RTK systems. Digital sounding measurements taken by hydrolite are compared to manual lead line measurements. Single RTK and Network RTK results differed in the order of tenth of a foot accuracy for horizontal coordinates and for height measurements variations can go up to several tenths. Sounding results indicate a best-fit trend line with a slope of 0.993, and an R squared value of 0.972, demonstrating that hydrolite measurements and manually collected depths at this site are well correlated.

Background: Co-occurrence of posttraumatic stress disorder (PTSD) in psychosis (estimated as 12%) raises personal suffering and societal costs. Health–economic studies on PTSD treatments in patients with a diagnosis of a psychotic disorder have not yet been conducted, but are needed for guideline development and implementation. This study aims to analyse the cost-effectiveness of guideline PTSD therapies in patients with a psychotic disorder. Methods: This health–economic evaluation alongside a randomized controlled trial included 155 patients with a psychotic disorder in care as usual (CAU), with comorbid PTSD. Participants received eye movement desensitization and reprocessing (EMDR) (n = 55), prolonged exposure (PE) (n = 53) or waiting list (WL) (n = 47) with masked assessments at baseline (T0) and at the two-month (post-treatment, T2) and six-month follow-up (T6). Costs were calculated using the TiC-P interview for assessing healthcare consumption and productivity losses. Incremental cost-effectiveness ratios and economic acceptability were calculated for quality-adjusted life years (EQ-5D-3L-based QALYs) and PTSD ‘Loss of diagnosis’ (LoD, CAPS). Results: Compared to WL, costs were lower in EMDR (-€1410) and PE (-€501) per patient per six months. In addition, EMDR (robust SE 0.024, t = 2.14, p = .035) and PE (robust SE 0.024, t = 2.14, p = .035) yielded a 0.052 and 0.051 incremental QALY gain, respectively, as well as 26% greater probability for LoD following EMDR (robust SE = 0.096, z = 2.66, p = .008) and 22% following PE (robust SE 0.098, z = 2.28, p = .023). Acceptability curves indicate high probabilities of PTSD treatments being the better economic choice. Sensitivity analyses corroborated these outcomes. Conclusion: Adding PTSD treatment to CAU for individuals with psychosis and PTSD seem to yield better health and less PTSD at lower costs, which argues for implementation.

Background: Despite robust empirical support for the efficacy of trauma-focused treatments, the dissemination proves difficult, especially in relation to patients with comorbid psychosis. Many therapists endorse negative beliefs about the credibility, burden, and harm of such treatment. Objective: This feasibility study explores the impact of specialized training on therapists’ beliefs about trauma-focused treatment within a randomized controlled trial. Method: Therapist-rated (n=16) credibility, expected burden, and harm expectancies of trauma-focused treatment were assessed at baseline, post-theoretical training, post-technical training, post-supervised practical training, and at 2-year follow-up. Credibility and burden beliefs of therapists concerning the treatment of every specific patient in the trial were also assessed. Results: Over time, therapist-rated credibility of trauma-focused treatment showed a significant increase, whereas therapists’ expected burden and harm expectancies decreased significantly. In treating posttraumatic stress disorder (PTSD) in patients with psychotic disorders (n=79), pre-treatment symptom severity was not associated with therapist-rated credibility or expected burden of that specific treatment. Treatment outcome had no influence on patient-specific credibility or burden expectancies of therapists. Conclusions: These findings support the notion that specialized training, including practical training with supervision, has long-term positive effects on therapists’ credibility, burden, and harm beliefs concerning trauma-focused treatment.

Background: Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1−/− retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling. Methods: Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data. Findings: RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1−/− tumors seemed more dichotomous, differences within the RB1−/− tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared with tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations. Interpretation: Molecular, clinical and histopathological differences between RB1−/− tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression. Research in context: Retinoblastoma is an ocular childhood cancer commonly caused by mutations in the RB1 gene. In order to determine optimal treatment, tumor subtyping is considered critically important. However, except for very rare retinoblastomas without an RB1 mutation, there are controversies as to whether subtypes of retinoblastoma do exist. Our study shows that retinoblastomas are highly diverse but rather than reflecting distinct tumor types with a different etiology, our data suggests that this diversity is a result of tumor progression driven by cumulative genetic alterations. Therefore, retinoblastomas should not be categorized in distinct subtypes, but be described according to their stage of progression.

BACKGROUND:While RB1 loss initiates retinoblastoma development, additional somatic copy number alterations (SCNAs) can drive tumor progression. Although SCNAs have been identified with good concordance between studies at a cytoband resolution, accurate identification of single genes for all recurrent SCNAs is still challenging. This study presents a comprehensive meta-analysis of genome-wide SCNAs integrated with gene expression profiling data, narrowing down the list of plausible retinoblastoma driver genes. METHODS:We performed SCNA profiling of 45 primary retinoblastoma samples and eight retinoblastoma cell lines by high-resolution microarrays. We combined our data with genomic, clinical and histopathological data of ten published genome-wide SCNA studies, which strongly enhanced the power of our analyses (N = 310). RESULTS:Comprehensive recurrence analysis of SCNAs in all studies integrated with gene expression data allowed us to reduce candidate gene lists for 1q, 2p, 6p, 7q and 13q to a limited gene set. Besides the well-established driver genes RB1 (13q-loss) and MYCN (2p-gain) we identified CRB1 and NEK7 (1q-gain), SOX4 (6p-gain) and NUP205 (7q-gain) as novel retinoblastoma driver candidates. Depending on the sample subset and algorithms used, alternative candidates were identified including MIR181 (1q-gain) and DEK (6p gain). Remarkably, our study showed that copy number gains rarely exceeded change of one copy, even in pure tumor samples with 100% homozygosity at the RB1 locus (N = 34), which is indicative for intra-tumor heterogeneity. In addition, profound between-tumor variability was observed that was associated with age at diagnosis and differentiation grades. INTERPRETATION:Since focal alterations at commonly altered chromosome regions were rare except for 2p24.3 (MYCN), further functional validation of the oncogenic potential of the described candidate genes is now required. For further investigations, our study provides a refined and revised set of candidate retinoblastoma driver genes.

The robustness analysis results obtained from a Global Positioning System (GPS) network are dramatically influenced by the configurationof the observed baselines. The selection of optimal GPS baselines may allow for a cost effective survey campaign and a sufficiently robustnetwork. Furthermore, using the approach described in this paper, the required number of sessions, the baselines to be observed, and thesignificance levels for statistical testing and robustness analysis can be determined even before the GPS campaign starts. In this study, wepropose a robustness criterion for the optimal design of geodetic networks, and present a very simple and efficient algorithm based on thiscriterion for the selection of optimal GPS baselines. We also show the relationship between the number of sessions and the non-centralityparameter. Finally, a numerical example is given to verify the efficacy of the proposed approach.

Recently, many organizations have begun providing online GNSS (Global Navigation Satellite System) data processing services. Currently, only one of these organizations i.e., OPUS (On-line Positioning Users Service) provides a rapid static data processing option. In case of static online data processing, the users are required to submit at least two hours of data to get reasonably precise results. To provide processing option with less than two hours of data, NGS (National Geodetic Survey) developed OPUS–RS for rapid static data processing so that usersmay submit as little as 15 minutes of dual frequency GNSS data. In this study, multiple observation sessions are conducted at the same locations to compare OPUS-RS generated coordinates among the different sessions to see whether separate values agree with each other. The results indicate that with OPUS-RS results the differences in horizontal coordinates agree with each other within 3.5 cm and vertical coordinates agree within 7.2 cm. For an independent check, OPUS-RS results are also compared against LGO(Leica Geo Office) produced Static results; this comparison yielded up to 4.5 cm variations among horizontal coordinate differences and variations among vertical coordinate differences are up to 11.4 cm.

Aquatic ecosystems are large contributors to global methane (CH4) emissions. Eutrophication significantly enhances CH4-production as it stimulates methanogenesis. Mitigation measures aimed at reducing eutrophication, such as the addition of metal salts to immobilize phosphate (PO43−), are now common practice. However, the effects of such remedies on methanogenic and methanotrophic communities—and therefore on CH4-cycling—remain largely unexplored. Here, we demonstrate that Fe(II)Cl2 addition, used as PO43- binder, differentially affected microbial CH4 cycling-processes in field experiments and batch incubations. In the field experiments, carried out in enclosures in a eutrophic pond, Fe(II)Cl2 application lowered in-situ CH4 emissions by lowering net CH4-production, while sediment aerobic CH4-oxidation rates—as found in batch incubations of sediment from the enclosures—did not differ from control. In Fe(II)Cl2-treated sediments, a decrease in net CH4-production rates could be attributed to the stimulation of iron-dependent anaerobic CH4-oxidation (Fe-AOM). In batch incubations, anaerobic CH4-oxidation and Fe(II)-production started immediately after CH4 addition, indicating Fe-AOM, likely enabled by favorable indigenous iron cycling conditions and the present methanotroph community in the pond sediment. 16S rRNA sequencing data confirmed the presence of anaerobic CH4-oxidizing archaea and both iron-reducing and iron-oxidizing bacteria in the tested sediments. Thus, besides combatting eutrophication, Fe(II)Cl2 application can mitigate CH4 emissions by reducing microbial net CH4-production and stimulating Fe-AOM. [ABSTRACT FROM AUTHOR]

The National Geodetic Survey began publishing a series of experimental geoid (xGEOID) models annually since 2014. The latest experimental model is xGEOID20. The San Joaquin Experimental Range (SJER) in Fresno County, California is surveyed using Static GPS and precise levelling and a local geoid (SJER Geoid) is created. In this study, SJER Geoid is compared against xGEOID20A&B models and the results are tabulated. The results indicate that xGEOID20A&B slopes agree with the GPS/levelling data well even in such a small area. SJER Geoid model agrees with the xGEOID20 models at 7 mm level. The biases about 80 cm are within the expected range between the North American Vertical Datum of 1988 (NAVD88) and North American-Pacific Geopotential Datum of 2022 (NAPGD2022). [ABSTRACT FROM AUTHOR]

With the intention to reveal the effect of the substitution, Ti-doped InSb alloy, we accomplished a first-principles prediction within the FPLAPW+lo method. We used GGA-PBEsol scheme attached with the improved TB-mBJ approach to predict structural, electronic, and magnetic properties of In1-xTixSb with concentration x = 0, 0.125, 0.25, 0.50, 0.75, 0.875, and 1. Our lattice parameters are found in favorable agreement with the available theoretical and experimental data. The calculation shows that all structures are energetically stable. The substitutional doping transforms the ionic character of the InSb compound in half-metallic ferromagnetic comportment for concentration x = 0, 0.125, 0.25, and 0.50, with a spin polarization of 100% at the Fermi level, and metallic nature for In0.25Ti0.75Sb and In0.125Ti0.875Sb. The total magnetic moments are also estimated at about 1 μB. In0.875Ti0.125Sb, In0.75Ti0.25Sb, and In0.50Ti0.50Sb have half-metallic ferromagnets comportment and they can be upcoming applicants for spintronics applications. [ABSTRACT FROM AUTHOR]