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Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.

Objective To identify the factors related to sleep duration in 3-month-old infants.

Summary: Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (Re) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low Re values. Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. Funding: National Health and Medical Research Council, Australian Research Council.

BackgroundMany autistic children experience motor skill deficits which can impact other areas of functioning, and research on therapeutic interventions for motor skills in autism is in a preliminary stage. Music-based therapies have been used extensively to address motor skills in non-autistic populations. Though a handful of studies exist on the effects of music-based therapies for movement in autistic children, none have investigated the possibility of administering sessions via telehealth. This mixed-methods pilot study investigated whether nine Neurologic Music Therapy (NMT)® sessions via telehealth would improve motor and attention skills in autistic children.MethodsFive autistic children between five and 10 years of age participated in the study, with support from their caregivers. Motor skills were assessed using the Bruininks-Oseretsky Test of Motor Proficiency second edition, short form (BOT-2 SF), and a selective attention and sustained attention task were taken from the Test of Everyday Attention for Children, Second Edition (TEA-Ch2). Caregivers and the two neurologic music therapists involved in the study provided qualitative input about the perceived effectiveness of telehealth NMT for the children involved. Their responses were analyzed using qualitative content analysis. Caregivers also filled out a Sensory Profile 2 assessment prior to the onset of sessions so that each child’s sensory profile could be compared to their motor and attention results.ResultsStatistically significant improvements in motor skills were observed between pre-test assessment and a two-week follow-up assessment. Results from attention test scores were not significant. Caregivers and neurologic music therapists generally perceived sessions positively and noted the importance of having caregivers actively involved. When compared with individual progress on the BOT-2 SF assessment, sensory profile results revealed that children with fewer sensory sensitivities tended to improve the most on motor skills. The improvements in motor skills and positive caregiver and therapist views of telehealth indicate that NMT motor interventions administered via telehealth are a promising avenue of therapeutic support for movement skill development in autistic children.

Introduction Cochlear implant (CI) activation usually takes place at ∼ 30 days postoperative (PO). In our service, CI surgery is performed with local anesthesia and sedation, so activation is possible with the patient's cooperation, immediately after the CI surgery, still in the operating room (OR).

IntroductionAutistic individuals demonstrate greater variability and timing error in their motor performance than neurotypical individuals, likely due at least in part to atypical cerebellar characteristics and connectivity. These motor difficulties may differentially affect discrete as opposed to continuous movements in autistic individuals. Augmented auditory feedback has the potential to aid motor timing and variability due to intact auditory-motor pathways in autism and high sensitivity in autistic individuals to auditory stimuli.MethodsThis experiment investigated whether there were differences in timing accuracy and variability in autistic adults as a function of task (discontinuous vs. continuous movements) and condition (augmented auditory feedback vs. no auditory feedback) in a synchronization-continuation paradigm. Ten autistic young adults aged 17–27 years of age completed the within-subjects study that involved drawing circles at 800 milliseconds intervals on a touch screen. In the discontinuous task, participants traced a series of discrete circles and paused at the top of each circle for at least 60 milliseconds. In the continuous task, participants traced the circles without pausing. Participants traced circles in either a non-auditory condition, or an auditory condition in which they heard a tone each time that they completed a circle drawing.ResultsParticipants had significantly better timing accuracy on the continuous timing task as opposed to the discontinuous task. Timing consistency was significantly higher for tasks performed with auditory feedback.DiscussionThis research reveals that motor difficulties in autistic individuals affect discrete timing tasks more than continuous tasks, and provides evidence that augmented auditory feedback may be able to mitigate some of the timing variability present in autistic persons’ movements. These results provide support for future investigation on the use of music-based therapies involving auditory feedback to address motor dysfunction in autistic individuals.

BackgroundThe Food and Drug Omnibus Report Act, signed into law in 2022, requires industry sponsors to include diversity action plans in clinical study protocols. Defining reliable methodology for measures and benchmarks is critical to ensuring adequate and consistent representation of historically underrepresented patient populations in clinical trials.MethodsWe provide an Advancing Inclusive Research (AIR) Calculator, summary tables, and data query bank to support target setting for the development of diversity action plans and to take steps toward defining enrollment standards. The AIR Calculator uses data from the US Cancer Statistics database, which covers 100% of the US population. The database provides descriptive statistics for people diagnosed with 26 different cancers from 2015-2019 by cancer site, age at diagnosis, sex, and race and ethnicity, all stratified by stage at diagnosis (early, de novo metastatic, and combined). Descriptive characteristics include frequency counts, age-adjusted incidence rates, incidence rate ratios, and 95% CIs. Robustness test results are available in the data query bank by year of diagnosis.ResultsThis resource offers insights into distributions of cancer in the US. The AIR Calculator allows users to calculate representative clinical study distributions based on the sponsor-designated study size.DiscussionThe AIR Calculator serves as a valuable resource for planning of clinical studies, but additional data analyses are necessary for a comprehensive understanding at the study level. Comprehensive data collection and alignment across industry are essential to ensure consistent, accurate, and transparent benchmarks in historically underrepresented patient populations and to track progress toward the goal of improving their representation in clinical research.

Volcanic eruptions are often preceded by episodes of in ation and emplacement of magma along tensile fractures. Here we study the 2021 Tajogaite-Cumbre Vieja eruption on La Palma, Canary Islands, and present evidence for tensile fractures dissecting the new cone during the terminal stage of the eruption. We use synthetic aperture radar (SAR) observations, together with drone images and time-lapse camera data, to determine the timing, scale and complexities associated with a fracturing event, which is diverging at a topographic ridge. By comparing the field dataset with analogue models, we further explore the details of lens-shaped fractures that are characteristic for faults diverging at topographic highs and converging at topographic lows. The observations made at Cumbre Vieja and in our models are transferrable to other volcanoes and add further evidence that topography is substantially affecting the geometry and complexity of fractures and magma pathways, and the locations of eruptions.

DNAmix 2021 is a large-scale study conducted to evaluate the extent of consistency and variation among forensic laboratories in the interpretation of DNA mixtures, and to assess the effects of various potential sources of variability. This study utilized a multi-phasic approach designed to collect information about participating laboratories, laboratory policies, and their standard operating procedures (SOPs). It also characterizes the degree of variation in assessments of suitability and number of contributors as well as in comparisons and statistical analyses of DNA mixture profiles. This paper specifically details the study design and the data collected in the first two phases of the study: the Policies & Procedures (P&P) Questionnaire and the Casework Scenarios Questionnaire (CSQ). We report on the variation in policies and SOPs for 86 forensic laboratories—including information about their DNA workflows, systems, and type of statistics reported. We also provide details regarding various case-scenario specific decisions and the nature of mixture casework for 83 forensic laboratories. The data discussed in this article provide insight into the state of the field for forensic DNA mixture interpretation policies and SOPs at the time of the study (2021–2022).

Consumption of contaminated produce remains a leading cause of foodborne illness. Increasingly, growers are altering agricultural practices and farm environments to manage food-safety hazards, but these changes often result in substantial economic, social, and environmental costs. Here, we present a comprehensive evidence synthesis evaluating the efficacy of soil, non-crop vegetation, animal, landscape, and irrigation water management strategies aimed at reducing produce-safety risk in North America. We systematically summarized findings from 78 peer-reviewed papers on the effect of 21 management practices on the prevalence, abundance, or survival of four foodborne pathogens (i.e., E. coli, Salmonella spp., Listeria spp., and Campylobacter spp.), resulting in 113 summaries. We then organized a 30-member expert panel, who used these summaries to evaluate the impact of each practice on food-safety outcomes. While more than half of the practices were too understudied to confidently evaluate their impact on food safety, the panel did identify several practices that were associated with reduced preharvest food-safety risks, including not using raw manure, separating crop and livestock production, and choosing low-risk irrigation sources. The panel also identified practices that appear ineffective at reducing food-safety risks, such as the removal of non-crop vegetation. Overall, these findings provide insights into the food-safety impacts of agricultural and land management practices that growers, auditors, and extension personnel can use to co-manage produce preharvest environments for food safety and other aims.

Abstract Biomaterials are implanted in millions of individuals worldwide each year. Both naturally derived and synthetic biomaterials induce a foreign body reaction that often culminates in fibrotic encapsulation and reduced functional lifespan. In ophthalmology, glaucoma drainage implants (GDIs) are implanted in the eye to reduce intraocular pressure (IOP) in order to prevent glaucoma progression and vision loss. Despite recent efforts towards miniaturization and surface chemistry modification, clinically available GDIs are susceptible to high rates of fibrosis and surgical failure. Here, we describe the development of synthetic, nanofiber‐based GDIs with partially degradable inner cores. We evaluated GDIs with nanofiber or smooth surfaces to investigate the effect of surface topography on implant performance. We observed in vitro that nanofiber surfaces supported fibroblast integration and quiescence, even in the presence of pro‐fibrotic signals, compared to smooth surfaces. In rabbit eyes, GDIs with a nanofiber architecture were biocompatible, prevented hypotony, and provided a volumetric aqueous outflow comparable to commercially available GDIs, though with significantly reduced fibrotic encapsulation and expression of key fibrotic markers in the surrounding tissue. We propose that the physical cues provided by the surface of the nanofiber‐based GDIs mimic healthy extracellular matrix structure, mitigating fibroblast activation and potentially extending functional GDI lifespan.

Formalised elicitation of expert judgements has been used to help tackle several problematic societal issues, including volcanic crises and pandemic threats. We present an expert elicitation exercise for Piton de la Fournaise volcano, La Réunion island, held remotely in April 2021. This involved 28 experts from nine countries who considered a hypothetical effusive eruption crisis involving a new vent opening in a high-risk area. The tele-elicitation presented several challenges, but is a promising and workable option for application to future volcanic crises. Our exercise considered an “uncommon” eruptive scenario with a vent outside the present caldera and within inhabited areas, and provided uncertainty ranges for several hazard-related questions for such a scenario (e.g. probability of eruption within a defined timeframe; elapsed time until lava flow reaches a critical location, and other hazard management issues). Our exercise indicated that such a scenario would probably present very different characteristics compared to recent eruptions, and that it is fundamental to include well-prepared expert elicitations in updated civil protection evacuation plans to improve disaster response procedures.

PURPOSEIn patients with advanced non–small-cell lung cancer (aNSCLC), tumor mutational burden (TMB) may vary by genomic ancestry; however, its impact on treatment outcomes is unclear. This retrospective, observational study describes treatment patterns of patients with aNSCLC by genomic ancestry and electronic health record (EHR)-reported race and/or ethnicity and evaluates differences in TMB, cancer immunotherapy (CIT) access, and treatment outcomes across racial and ancestral groups.METHODSPatients diagnosed with aNSCLC after January 1, 2011, were selected from a real-world deidentified clinicogenomics database and EHR-derived database; continuously enrolled patients were evaluated. Race and/or ethnicity was recorded using variables from the EHR database; genomic ancestry was classified by single-nucleotide polymorphisms on a next-generation sequencing panel. A threshold of 16 mutations per megabase was used to categorize TMB status.RESULTSOf 59,559 patients in the EHR-derived database and 7,548 patients in the clinicogenomics database, 35,016 (58.8%) and 4,392 (58.2%) were continuously enrolled, respectively. CIT use was similar across EHR-reported race groups, ranging from 34.4% to 37.3% for non-Hispanic Asian and non-Hispanic Black patients, respectively. TMB levels varied significantly across ancestry groups (P < .001); patients of African ancestry had the highest median TMB (8.75 mutations per megabase; interquartile range, 4.35-14.79). In patients who had received CIT, high TMB was associated with improved overall survival compared with low TMB (20.89 v 11.83 months; hazard ratio, 0.60; 95% CI, 0.51 to 0.70) across genomic ancestral groups.CONCLUSIONThese results suggest that equitable access to next-generation sequencing may improve aNSCLC outcome disparities in racially and ancestrally diverse populations.

Previously the effect of the pruritogens, such as histamine and chloroquine, was tested in 11 inbred mouse strains, and this study aimed to identify resistant and sensitive strains, consistent with the observation that underlies the large variability in human populations. In the present study, we used the low responder C3H/HeJ (C3H) and the more sensitive C57BL/6J (C57) strain to find out if resistance and sensitivity to develop pruritus is restricted to only histamine and chloroquine or extends to other known pruritogens as well. We tested five additional commonly known pruritogens. We established dose-response relationships by injecting four concentrations of the pruritogens in the range of 0.3, 1, 3, and ten-fold in the nuchal fold. Then we assessed the scratching behavior for 30 min after injection with an automated custom-designed device based on the bilateral implantation of mini-magnets in the hind paws and on single cages placed within a magnetic coil. We found that the resistance to pruritogens is a general phenotype of the C3H strain and extends to all pruritogens tested, including not only histamine and chloroquine, but also endothelin, trypsin, 5-HT (serotonin), the short peptide SLIGRL, and Lysophosphatidic acid (LPA). C57 was more sensitive to all pruritogens and, in contrast to C3H, dose-response relationships were evident for some of the pruritogens. In general, comparable peak scratch responses were observed for the 0.3-fold concentrations of the pruritogens in C57 whereas C3H required at least the ten-fold concentration and still displayed only between 5 and 33% of the scratch responses observed in C57 for the respective pruritogen. The general resistance to pruritogens and the low level of scratching behavior found in the C3H strain is an interesting trait and represents a model for the study of the heritability of itch. It is accompanied in C3H with a higher sensitivity in assays of nociception.

Abstract Aims To identify image quality criteria that can be applied to assess breast implant (BI) mammograms according to radiologists and radiographers’ perspectives and to explore the level of agreement about criteria priority. Methods A two-round Delphi method using a questionnaire was applied to identify the level of agreement between experts, asking them to rank each image criteria available for mammography according to 4 possible answers (1 = need to have, 2 = nice to have, 3 = not pertinent/appropriate, 4 = do not know). Criteria for craniocaudal (CC), mediolateral-oblique (MLO) and lateral (ML), with and without Eklund manoeuvre, were included. This process was repeated after removing the less relevant criteria. Results Between first and second rounds, different results were obtained regarding the criteria to assess CC and MLO images. Details for anatomic areas were considered the most relevant by radiographers during the first round, while general criteria were prioritised during the second round. Radiologists focused more on analysis of the spread of the breast tissue, if the breast was aligned with detector’s centre and level of contrast. The analysis of implant flow, the BI anterior edge and the maximum retropulsion of BI when Eklund manoeuvre is performed were the specific aspects of BI imaging considered as relevant for assessment. Conclusions The importance of each criterion used to assess BI mammograms was not the same between radiographers and radiologists, suggesting the two groups of experts are looking for different requirements from the image. Further education and training is necessary to align strategies for assessing BI mammograms, and some criteria need to be adapted to reduce subjectivity.

Abstract Purpose To characterise the mammography technique used in breast cancer screening programmes for breast implants (BI) and to identify if the image quality (IQ) criteria available in literature are applicable to BI imaging. Methods The study was conducted in two phases: literature review to find IQ criteria used in mammography combining keywords in several sources; and assessment of 1207 BI mammograms using the criteria that was identified previously to see if they were achieved or not. An observation grid was used to collect information about positioning, beam energy, compression force, and exposure mode. Descriptive statistics and Student’s t test and χ2 test were performed according to the nature of the variables. Results Forty-seven out of 2188 documents were included in the analysis, with 13 items identified to assess the quality of positioning, 4 for sharpness, 3 for artefacts, and 2 for exposure parameters. After applying the criteria to BI mammograms, retroglandular fat was not included in 37.3% of the images. The “Pectoral-Nipple-Line” criterion was achieved in 35% of MLO/ML images. The placement of the implant (subpectoral/subglandular) or performing the Eklund had significant influence on the visible anatomy (p = < 0.005), alongside whether the breast was aligned to the detector’s centre. Conclusions Some of the criteria used to assess standard mammograms were not applicable to BI due to implant overlap. The alignment of the image with the detector’s centre seems to have an impact on the amount of visible tissue. Further studies are necessary to define the appropriate protocol, technique, and suitable quality criteria to assess BI mammograms.

Abstract Objectives This pilot study aimed to characterize and compare radiographers’ mammography practice, including quality control and continuous professional development in five European countries. Methods Online survey was performed to collect data regarding participants’ profile, institution’s profile, mammography practice, quality control and continuous professional development. The questionnaire was sent to clinical radiographers working in Estonia, Finland, Norway, Portugal and Switzerland. Descriptive statistical and subgroup analyzes were performed. Results The amount of returned questionnaires was 140. Most respondents were female (92%), having radiography bachelor. The majority (89%) of radiographers was working with full-field digital mammography. The majority (97%) of mammography images were acquired using AEC, and half of the radiographers were using dose saving programmes suggested by the manufacturers. The most typical (50%) compression force ranged from 8 to 11 kg. Part of the radiographers (44%) did not know if their practice followed specific guidelines. The most challenging tasks in mammography identified by radiographers were patient positioning (86%), coping with pain (88%), managing anxiety (83%) and imaging breast implants (71%). The majority (88%) of the respondents undertook continuous professional development activities. Conclusions The mammography practice varies across the five countries. We found country-specific traits related to mammography image acquisition, patient-centered care and quality management procedures. The lack of evidence-based knowledge suggests the importance of well-designed studies on these topics. The variability found in this pilot study encourages radiographers to question their own practice and teachers to review and revise the training programmes. Validation in larger studies including more countries is needed.

Respiratory syncytial virus is a common cause of bronchiolitis. Historically, point-of-care tests have involved antigen detection technology with limited sensitivity. The aim of this study was to prospectively evaluate the diagnostic accuracy and model the economic impact of the Roche cobas® Liat® point-of-care influenza A/B and respiratory syncytial virus test. The “DEC-RSV” study was a multi-centre, prospective, observational study in children under 2 years presenting with viral respiratory symptoms. A nasopharyngeal aspirate sample was tested using the point-of-care test and standard laboratory-based procedures. The primary outcome was accuracy of respiratory syncytial virus detection. The cost implications of adopting a point-of-care test were modelled using study data. A total of 186 participants were recruited, with both tests performed on 177 samples. The point-of-care test was invalid for 16 samples (diagnostic yield 91%) leaving 161 available for primary analysis. After resolving discrepancies, the cobas® Liat® respiratory syncytial virus test had 100.00% (95% CI 96.07%–100.00%) sensitivity and 98.53% (95% CI 92.08%–99.96%) specificity. Median time to result was 0.6 h (interquartile range (IQR) 0.5–1) for point-of-care testing and 28.9 h (IQR 26.3–48.1) for standard laboratory testing. Estimated non-diagnostic cost savings for 1000 patients, based on isolation decision-making on point-of-care test result, were £57 010, which would increase to £94 847 when cohort nursing is used. In young children the cobas® Liat® point-of-care respiratory syncytial virus test has high diagnostic accuracy using nasopharyngeal aspirates (currently an off-licence sample type). Time to result is clinically important and was favourable compared to laboratory-based testing. The potential exists for cost savings when adopting the point-of-care test.

Background: Study populations in clinical research must reflect US changing demographics, especially with the rise of precision medicine. However, racial and ethnic minority groups (REMGs) have low rates of participation in cancer clinical trials. Methods: Criteria were developed to identify cancer centers able to accrue a higher than average proportion of REMGs into clinical trials. Comprehensive interviews were conducted with leaders of these cancer centers to identify operational strategies contributing to enhanced accrual of REMGs. Results: Eight US cancer centers reported a REMG accrual rate range in cancer research between 10 and 50% in a 12-month reporting period and met other criteria for inclusion. Fourteen leaders participated in this assessment. Key findings were that centers: had a metric collection and reporting approach; routinely captured race and ethnicity data within databases accessible to research staff; had operational standards to support access and inclusion; developed practices to facilitate sustained patient participation during clinical trials; had strategies to decrease recruitment time and optimize clinical study design; and identified low-resource strategies for REMG accrual. There was also a clear commitment to establish processes that support the patient's provider as the key influencer of patient recruitment into clinical trials. Conclusion: We have identified operational practices that facilitate increased inclusion of REMGs in cancer trials. In order to establish a sustainable cancer center inclusion research strategy, it is valuable to include an operational framework that is informed by leading US cancer centers of excellence. Keywords: Cancer research, Clinical trials, Operations, Disparities, Diversity and inclusion, Racial and ethnic minority groups

Abstract Background The neuromuscular junction is the chemical synapse where motor neurons communicate with skeletal muscle fibers. Whereas vertebrates and many invertebrates use acetylcholine as transmitter at the neuromuscular junction, in those arthropods examined up to now, glutamate and GABA are used instead. With respect to taxon sampling in a phylogenetic context, there is, however, only a limited amount of data available, focusing mainly on crustaceans and hexapods, and neglecting other, arthropod groups. Here we investigate the neurotransmitter equipment of neuromuscular synapses of a myriapod, Lithobius forficatus, using immunofluorescence and histochemical staining methods. Results Glutamate and GABA could be found colocalised with synapsin in synaptic boutons of body wall and leg muscles of Lithobius forficatus. Acetylcholinesterase activity as a marker for cholinergic synapses was found abundantly in the central nervous system and also in some peripheral nerves, but not at neuromuscular junctions. Furthermore, a large number of leg sensory neurons displayed GABA-immunofluorescence and was also labeled with an antiserum against the GABA-synthesizing enzyme, glutamate decarboxylase. Conclusions Our data indicate that glutamate and GABA are neurotransmitters at Lithobius forficatus neuromuscular junctions, whereas acetylcholine is very unlikely to play a role here. This is in line with the concept of glutamate as excitatory and GABA as the main inhibitory neuromuscular transmitters in euarthropods. Furthermore, we have, to our knowledge for the first time, localized GABA in euarthropod leg sensory neurons, indicating the possibility that neurotransmitter panel in arthropod sensory systems may be far more extensive than hitherto assumed.

Abstract Background Melanoma is a rare, deadly disease without effective treatment options in China. Vemurafenib is a selective inhibitor of oncogenic BRAF V600 kinase approved in more than 90 countries, based on results obtained primarily in Caucasian patients. Limited data are available regarding the efficacy and safety of vemurafenib in Asian patients. Methods This phase I study investigated the pharmacokinetics, efficacy, and tolerability of vemurafenib (960 mg twice daily) in Chinese patients with BRAF V600 mutation–positive unresectable or metastatic melanoma. The study included two cohorts: a pharmacokinetic cohort (n = 20) and an expansion cohort (n = 26). Results After 21 days of dosing, vemurafenib demonstrated marked accumulation and relatively constant steady-state exposure over the dosing period. Confirmed best overall response rate was 52.2% (95% CI 37.0–67.1%). Median progression-free survival was 8.3 months (95% CI 5.7–10.9%); median overall survival was 13.5 months (95% CI 12.2%–not estimable). The most common adverse events were dermatitis acneiform, arthralgia, diarrhea, blood cholesterol level increase, blood bilirubin level increase, melanocytic nevus, and alopecia. A total of nine grade 3 or 4 adverse events were reported in seven patients (15.2%). Conclusion Overall, vemurafenib showed a favorable benefit-risk profile among Chinese patients. Pharmacokinetics, safety, and efficacy were generally consistent with those reported in Caucasian patients. Trial registration ClinicalTrials.gov identification: NCT01910181. Registered 29 July 2013, prospectively registered.

Flank instability and lateral collapse are a potential hazard at volcanic edifices. Here, the authors use numerical simulations to show that at Fogo volcano, lateral collapse can trigger a significant deflection of magma pathways in the crust, demonstrating how volcanic edifices may evolve.

Abstract Objectives This study aims to identify European radiographers’ challenges in clinical performance in mammography and the main areas of mammography that require more and better training. Methods An extensive search was performed to identify relevant studies focused on clinical practice, education and training in mammography published between January 2010 and December 2015 in the English language. The data were analysed by using deductive thematic analysis. Results A total of 27 full text articles were read, evaluating their quality. Sixteen articles out of 27 were finally selected for this integrative review. The main challenges of radiographers’ mammography education/training can be divided into three groups: training needs, challenges related to radiographers, and challenges related to the organization of education. The most common challenges of clinical performance in mammography among European radiographers involved technical performance, the quality of practices, and patient-centeredness. Conclusions The introduction of harmonized mammography guidelines across Europe may serve as an evidence-based tool to be implemented in practice and education. However, the variability in human and material resources as well as the different cultural contexts should be considered during this process. Teaching Points • Radiographers’ awareness of their professional identity and enhancing multiprofessional cooperation in mammography. • Radiographers’ responsibilities regarding image quality (IQ) and optimal breast imaging performance. • Patient-centred mammography services focusing on the psychosocial needs of the patient. • Challenges: positioning, QC-testing, IQ-assessment, optimization of breast compression, communication, teamwork, and patient-centred care. • Introduction of evidence-based guidelines in Europe to harmonize mammography practice and education.

A state brand was created for Rhode Island (RI) seafood in an effort to encourage the development of the fishing and aquaculture industries. Little was done to assess RI consumers, however, regarding their perceptions and understanding of local sea­food. Therefore, a survey (N=968) of RI consum­ers at least 18 years old was implemented to assess consumer perceptions, purchasing choices, and understanding of local seafood. The majority of RI consumers, regardless of income, education, and locality, would prefer local seafood if they could easily find it in the market and if they could trust the brand to identify product choices. The top three places to purchase seafood were supermar­kets, seafood specialty stores, and restaurants. Sea­food quality, taste preference, safety at pur­chase, and absence of contaminants were con­sidered important or very important factors influ­encing purchasing decisions; however, respondents felt only somewhat knowledgeable about key sea­food attributes. More than half of survey consum­ers (66%) felt that the branding logo, created by the RI Department of Environmental Manage­ment, would encourage them to select a local sea­food product, and 53% indicated they would be more willing to try a seafood product if it were labeled local. However, only 12% of respond­ents recog­nized the brand for local RI seafood. This informa­tion will be used by state partners to help develop an outreach strategy to promote the RI seafood brand and local seafood and will be used to inform current policy regarding branding.

Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the molecules with specifically positioned fluorine atoms in order to control the molecular conformations. The fluorinated analogs were screened against a panel of 11 HDAC isoforms, and minor differences in isoform selectivity patterns were observed.

Synthetic Aperture Radar (SAR) remote sensing plays a significant role in volcano monitoring despite the measurements’ non real-time nature. The technique’s capability of imaging the spatial extent of ground motion has especially helped to shed light on the location, shape, and dynamics of subsurface magmatic storage and transport as well as the overall state of activity of volcanoes worldwide. A variety of different deformation phenomena are observed at exceptionally active and frequently erupting volcanoes, like Piton de la Fournaise on La Réunion Island. Those offer a powerful means of investigating related geophysical source processes and offer new insights into an active volcano’s edifice architecture, stability, and eruptive behavior. Since 1998, Interferometric Synthetic Aperture Radar (InSAR) has been playing an increasingly important role in developing our present understanding of the Piton de la Fournaise volcanic system. We here collect the most significant scientific results, identify limitations, and summarize the lessons learned from exploring the rich Piton de la Fournaise SAR data archive over the past ~20 years. For instance, the technique has delivered first evidence of the previously long suspected mobility of the volcano’s unsupported eastern flank, and it is especially useful for detecting displacements related to eruptions that occur far away from the central cone, where Global Navigation Satellite System (GNSS) stations are sparse. However, superimposed deformation processes, dense vegetation along the volcano’s lower eastern flank, and turbulent atmospheric phase contributions make Piton de la Fournaise a challenging target for applying InSAR. Multitemporal InSAR approaches that have the potential to overcome some of these limitations suffer from frequent eruptions that cause the replacement of scatterers. With increasing data acquisition rates, multisensor complementarity, and advanced processing techniques that resourcefully handle large data repositories, InSAR is progressively evolving into a near-real-time, complementary, operational volcano monitoring tool. We therefore emphasize the importance of InSAR at highly active and well-monitored volcanoes such as Mount Etna, Italy, Kīlauea Volcano, Hawai’i, and Piton de la Fournaise, La Réunion.

Abstract Introduction Otosclerosis is a disease that causes bone resorption and deposition in the auditory structures, leading to deafness. Many studies have evaluated the histopathology of the stapes footplate in this disease (osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes), but we found no studies in the literature involving the histology of the superstructure of the stapes. Objectives To perform an analysis under optical microscopy of histopathologic findings of the superstructure of the stapes from patients with otosclerosis. Methods A contemporary cross-sectional cohort study of pathology analysis of superstructures of the stapes of patients with otosclerosis. Results Fifteen superstructures of stapes in patients with otosclerosis operated in our service and four stapes of cadavers used for dissection (controls) were evaluated. No areas of bone resorption or deposition or presence of osteoclasts and osteoblasts in the superstructure of the stapes were found. However, we found in the more distal portions of the crura areas with prominent cementitious lines and woven bone, which was different than the mature trabecular bone found in the head of the stapes or in the controls. Conclusion There were histologic changes in the superstructure of the stapes in patients with otosclerosis operated in our service.

Background: The recently postulated disease spreading hypothesis has gained much attention, especially for Parkinson’s disease (PD). The various nonmotor symptoms (NMS) in neurodegenerative diseases would be much better explained by this hypothesis than by the degeneration of disease-specific cell populations. Motor neuron disease (MND) is primarily known as a group of diseases with a selective loss of motor function. Recent evidence, however, suggests disease spreading into nonmotor brain regions also in MND. The aim of this study was to comprehensively detect NMS in patients suffering from MND.Methods: We used a self-rating questionnaire including 30 different items of gastrointestinal, autonomic, neuropsychiatric and sleep complaints (NMSQuest) which is an established tool in PD patients. 90 MND patients were included and compared to 96 controls.Results: In total, MND patients reported significantly higher NMS scores (median: 7 points) in comparison to controls (median: 4 points). Dribbling, impaired taste/smelling, impaired swallowing, weight loss, loss of interest, sad/blues, falling and insomnia were significantly more prevalent in MND patients compared to controls. Interestingly excessive sweating was more reported in the MND group. Correlation analysis revealed an increase of total NMS score with disease progression.Conclusions: NMS in MND patients seemed to increase with disease progression which would fit with the recently postulated disease spreading hypothesis. The total NMS score in the MND group significantly exceeded the score for the control group, but only 8 of the 30 single complaints of the NMSQuest were significantly more often reported by MND patients. Dribbling, impaired swallowing, weight loss and falling could primarily be connected to motor neuron degeneration and declared as motor symptoms in MND.

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Se tomó una biopsia de un abultamiento en el área nasofacial de un ovino hembra, preñada, mestiza West African de tres 3 años de edad y 25 Kg. De peso. Al examen directo del exudado de observaron abundantes levaduras encapsuladas características del Cryptococcus neoformans (C. neoformans), la cepa fue aislada en agar dextrosa Sabouraud (SDA) y crecida en agar niger. Se realizó una evaluación histopatológica de la biopsia, obervándose numerosas levaduras encapsuladas en una malla de tejido conectivo fibroso con gran cantidad de leucocitos (neutrófilos, macrófagos y linfocitos) en el área de la dermis. El animal fue sacrificado posterior al parto, presentando evidencia de caquexia avanzada e inanición. Se realizaron evaluaciones macroscópicas e histopatológicas, observando una masa de tejido blando, mucinoso, gelatinoso, de color gris ambarino, cubierta por epitello cutáneo lacerado en el área nasofacial izquierda. Histopatológicamente la masa estaba constituida por tejido fibroconectivo laxo mucinoso, en forma de malla, había gran cantidad de células inflamatorias similaes a las de la biopsia, en conjunto con estructuras levaduriformes translúcidas, encapsuladas, de 3 a 9 micras de diámetro, con colágeno y fibrositos. Se realizó coloración especial de Mucicarmín, evidenciando las características típicas del C. neoformans. La cepa aislada fue experimentalmente inoculada en ratones a nivel del área nasal, reproduciendo las lesiones en estos animales.