Phenotype-limited distributions: short-billed birds move away during times that prey bury deeply

In our seasonal world, animals face a variety of environmental conditions in the course of the year. To cope with such seasonality, animals may be phenotypically flexible, but some phenotypic traits are fixed. If fixed phenotypic traits are functionally linked to resource use, then animals should redistribute in response to seasonally changing resources, leading to a ‘phenotype-limited’ distribution. Here, we examine this possibility for a shorebird, the bar-tailed godwit (Limosa lapponica; a long-billed and sexually dimorphic shorebird), that has to reach buried prey with a probing bill of fixed length. The main prey of female bar-tailed godwits is buried deeper in winter than in summer. Using sightings of individually marked females, we found that in winter only longer-billed individuals remained in the Dutch Wadden Sea, while the shorter-billed individuals moved away to an estuary with a more benign climate such as the Wash. Although longer-billed individuals have the widest range of options in winter and could therefore be selected for, counterselection may occur during the breeding season on the tundra, where surface-living prey may be captured more easily with shorter bills. Phenotype-limited distributions could be a widespread phenomenon and, when associated with assortative migration and mating, it may act as a precursor of phenotypic evolution

Subtyping Cutaneous Melanoma Matters

Background: Our aim was to investigate the role of melanoma subtype on survival and focus on the effects stratified by Breslow thickness and ulceration status. Methods: Patients with cutaneous melanoma stage I, II, or III diagnosed between 2000 and 2014 were derived from the Dutch Nationwide Pathology Registry and overall survival data from the Netherlands Cancer Registry. Patients were followed until 2018. Using multivariable Cox proportional hazards models, hazard ratios were calculated for each melanoma subtype, per Breslow thickness category and ulceration status, and adjusted for age, sex, stage, and localization. Results: A total of 48 361 patients were included: 79.3% had superficial spreading melanoma (SSM), 14.6% nodular melanoma (NM), 5.2% lentigo maligna melanoma, and 0.9% acral lentiginous melanoma (ALM). In the total patient group, using SSM as the reference category, adjusted hazard ratios were 1.06 (95% confidence interval [CI] = 1.01 to 1.12) for NM, 1.02 (95% CI = 0.93 to 1.13) for lentigo maligna melanoma, and 1.26 (95% = CI 1.06 to 1.50) for ALM. Among patients with 1.0 mm or less Breslow thickness and no ulceration, NM showed a twofold increased risk (hazard ratio = 1.96, 95% CI = 1.58 to 2.45) compared with SSM. Compared with 1.0 mm or less SSM without ulceration, the hazard ratio for 1.0 mm or less SSM with ulceration was 1.94 (95% CI = 1.55 to 2.44), and the hazard ratio for 1.0 mm or less NM with ulceration was 3.46 (95% CI = 2.17 to 5.50). NM patients with tumors greater than 1.0 mm did not show worse survival than SSM patients with tumors greater than 1.0 mm. Conclusions: In this large nationwide study, ALM patients showed worse survival than SSM patients. Among patients with melanomas that were thin (1.0 mm or less), NM subtype patients also showed worse survival than SSM patients

Brain Damage and Visuospatial Impairments: Exploring Early Structure-Function Associations in Children Born Very Preterm

BACKGROUND: To provide insight into early neurosensory development in children born very preterm, we assessed the association between early structural brain damage and functional visuospatial attention and motion processing from one to two years corrected age. METHODS: In 112 children born at less than 32 weeks gestational age, we assessed brain damage and growth with a standardized scoring system on magnetic resonance imaging (MRI; 1.5 Tesla) scans performed at 29 to 35 weeks gestational age. Of the children with an MRI scan, 82 participated in an eye tracking-based assessment of visuospatial attention and motion processing (Tobii T60XL) at one year corrected age and 59 at two years corrected age. RESULTS: MRI scoring showed good intra- and inter-rater reproducibility. At one year, 10% children had delayed attentional reaction times and 23% had delayed motion reaction times. Moderate to severe brain damage significantly correlated with slower visuospatial reaction times. At two years, despite attention and motion reaction times becoming significantly faster, 20% had delayed attentional reaction times and 35% had delayed motion reaction times, but no correlations with MRI scores were found. The presence of structural brain damage was associated with abnormal functional performance over age. CONCLUSIONS: The present study indicates an association between moderate to severe brain damage and visuospatial attention and motion processing dysfunction at one year corrected age. This provides a new perspective on comprehensive MRI scoring and quantitative functional visuospatial assessments and their applicability in children born very preterm in their first years of life

Oncology patients were found to understand and accept the Trials within Cohorts design

Background and Objective: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting. Methods: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment). Results: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions,"10% felt reassured (6/62) and 2% scared/insecure (2/62). Conclusion: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications. (c) 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Body shrinkage due to Arctic warming reduces red knot fitness in tropical wintering range

Reductions in body size are increasingly being identified as a response to climatewarming. Here we present evidence for a case of such body shrinkage, potentially dueto malnutrition in early life. We show that an avian long-distance migrant (red knot,Calidris canutus canutus), which is experiencing globally unrivaled warming rates at itshigh-Arctic breeding grounds, produces smaller offspring with shorter bills duringsummers with early snowmelt. This has consequences half a world away at their tropicalwintering grounds, where shorter-billed individuals have reduced survival rates. This isassociated with these molluscivores eating fewer deeply buried bivalve prey and moreshallowly buried seagrass rhizomes. We suggest that seasonal migrants can experiencereduced fitness at one end of their range as a result of a changing climate at theother end

Integrated, multidisciplinary care for hand eczema: design of a randomized controlled trial and cost-effectiveness study

Background: The individual and societal burden of hand eczema is high. Literature indicates that moderate to severe hand eczema is a disease with a poor prognosis. Many patients are hampered in their daily activities, including work. High costs are related to high medical consumption, productivity loss and sick leave. Usual care is suboptimal, due to a lack of optimal instruction and coordination of care, and communication with the general practitioner/occupational physician and people involved at the workplace. Therefore, an integrated, multidisciplinary intervention involving a dermatologist, a care manager, a specialized nurse and a clinical occupational physician was developed. This paper describes the design of a study to investigate the effectiveness and cost-effectiveness of integrated care for hand eczema by a multidisciplinary team, coordinated by a care manager, consisting of instruction on avoiding relevant contact factors, both in the occupational and in the private environment, optimal skin care and treatment, compared to usual, dermatologist-led care. Methods: The study is a multicentre, randomized, controlled trial with an economic evaluation alongside. The study population consists of patients with chronic, moderate to severe hand eczema, who visit an outpatient clinic of one of the participating 5 (three university and two general) hospitals. Integrated, multidisciplinary care, coordinated by a care manager, including allergo-dermatological evaluation by a dermatologist, occupational intervention by a clinical occupational physician, and counselling by a specialized nurse on optimizing topical treatment and skin care will be compared with usual care by a dermatologist. The primary outcome measure is the cumulative difference in reduction of the clinical severity score HECSI between the groups. Secondary outcome measures are the patient's global assessment, specific quality of life with regard to the hands, generic quality of life, sick leave and patient satisfaction. An economic evaluation will be conducted alongside the RCT. Direct and indirect costs will be measured. Outcome measures will be assessed at baseline and after 4, 12, 26 and 52 weeks. All statistical analyses will be performed on the intention-to-treat principle. In addition, per protocol analyses will be carried out. Discussion: To improve societal participation of patients with moderate to severe hand eczema, an integrated care intervention was developed involving both person-related and environmental factors. Such integrated care is expected to improve the patients' clinical signs, quality of life and to reduce sick leave and medical costs. Results will become available in 2011

The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016

On 7-8 th November 2016, 60 people with an interest in the ‘ Trials within Cohorts ’ (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2 nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical frame- work, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day sympo- sium enabled an international group to meet and share experiences of the TwiCs design (also known as the ‘ cohort multiple RCT design ’ ), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini pre- sentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are ap- propriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis

Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

Recognition of patients with medically unexplained physical symptoms by family physicians: results of a focus group study

BACKGROUND: Patients with medically unexplained physical symptoms (MUPS) form a heterogeneous group and frequently attend their family physician (FP). Little is known about how FPs recognize MUPS in their patients. We conducted a focus group study to explore how FPs recognize MUPS and whether they recognize specific subgroups of patients with MUPS. Targeting such subgroups might improve treatment outcomes. METHODS: Six focus groups were conducted with in total 29 Dutch FPs. Two researchers independently analysed the data applying the principles of constant comparative analysis in order to detect characteristics to recognize MUPS and to synthesize subgroups. RESULTS: FPs take into account various characteristics when recognizing MUPS in their patients. More objective characteristics were multiple MUPS, frequent and long consultations and many referrals. Subjective characteristics were negative feelings towards patients and the feeling that the FP cannot make sense of the patient's story. Experience of the FP, affinity with MUPS, consultation skills, knowledge of the patient's context and the doctor-patient relationship seemed to influence how and to what extent these characteristics play a role. Based on the perceptions of the FPs we were able to distinguish five subgroups of patients according to FPs: 1) the anxious MUPS patient, 2) the unhappy MUPS patient, 3) the passive MUPS patient, 4) the distressed MUPS patient, and 5) the puzzled MUPS patient. These subgroups were not mutually exclusive, but were based on how explicit and predominant certain characteristics were perceived by FPs. CONCLUSIONS: FPs believe that they can properly identify MUPS in their patients during consultations and five distinct subgroups of patients could be distinguished. If these subgroups can be confirmed in further research, personalized treatment strategies can be developed and tested for their effectiveness

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics