Validation of an algorithm for automated classification of migraine and tension-type headache attacks in an electronic headache diary

Background: This study evaluates the accuracy of an automated classification tool of single attacks of the two major primary headache disorders migraine and tension-type headache used in an electronic headache diary. Methods: One hundred two randomly selected reported headache attacks from an electronic headache-diary of patients using the medical app M-sense were classified by both a neurologist with specialisation in headache medicine and an algorithm, constructed based on the ICHD-3 criteria for migraine and tension-type headache. The level of agreement between the headache specialist and the algorithm was compared by using a kappa statistic. Cases of disagreement were analysed in a disagreement validity assessment. Result: The neurologist and the algorithm classified migraines with aura (MA), migraines without aura (MO), tension-type headaches (TTH) and non-migraine or non-TTH events. Of the 102 headache reports, 86 cases were fully agreed on, and 16 cases not, making the level of agreement unweighted kappa 0.74 and representing a substantial level of agreement. Most cases of disagreement (12 out of 16) were due to inadvertent mistakes of the neurologist identified in the disagreement validity assessment. The second most common reason (3 out of 16) was insufficient information for classification by the neurologist. Conclusions: The substantial level of agreement indicates that the classification tool is a valuable instrument for automated evaluation of electronic headache diaries, which can thereby support the diagnostic and therapeutic clinical processes. Based on this study’s results, additional diagnostic functionalities of primary headache management apps can be implemented. Finally, future research can use this classification algorithm for large scale database analysis for epidemiological studies

Understanding demographic limiting factors to species recovery: Nest-site suitability and breeding ecology of Phelsuma guentheri on Round Island, Mauritius

The island of Mauritius in the Mascarenes has already suffered high levels of extinction, and habitat destruction and invasive alien species have pushed many of the remaining endemic species to the brink of extinction. Round Island, a small island northeast of Mauritius, is home to remnant populations of several reptile species that were once distributed across Mauritius. One of the most threatened of these is Günther’s gecko Phelsuma guentheri, where despite extensive management efforts, population size remains small and below expectation. We identify determinants of nest-site suitability across Round Island, and examine whether suitable nest sites are a limiting factor for the abundance of P. guentheri. Over one breeding season, we recorded and monitored a high number (269) of nest sites harbouring a total of 1475 eggs. We used the number of eggs at each nest, and the hatching success as proxies for nest-site suitability. To study the reproductive behaviour of P. guentheri, we installed trail cameras at three nest sites. We did not find the expected high frequency of use of hardwood trees as nest sites, as found on Ile aux Aigrettes to the southeast of Mauritius, probably because hardwood trees are still relatively sparse and small on Round Island. Instead, the endemic palm Latania loddigesii was the most used nest sites, harbouring 78.8% of all nests with 56.3% of all eggs. Hatching success was high for palm nest sites (90.6%), rock surfaces (91.8%), and on the endemic screw pine Pandanus vandermeeschii (96%), rates that are similar to that reported from hardwood trees on Ile aux Aigrettes (~90%). Communal nesting occurred on all substrates, with up to five individuals using the same nest site. Egg-laying took place at dusk or at night, lasting around 30 min, whereas hatching occurred mostly during the day, lasting 2–107 min. Females laid eggs every 34 days on average, and produced up to four clutches of 1–2 eggs each within the season. We conclude that P. guentheri does not suffer from nest site limitation on Round Island, and that reproductive success is high in terms of both numbers of eggs laid and hatching success, likely due to ongoing habitat restoration. Further research is needed to investigate the factors inhibiting abundance and distribution of P. guentheri on Round Island

Critical Mass in Inter-Organizational Platforms

This paper examines how the critical mass challenge manifests itself during inter-organizational platform development. In previous research, critical mass is treated as an issue that occurs after platform launch. Strategies proposed, such as tactful pricing, opening the platform, user onboarding, and side-switching assume the platform to have already been launched. They may not work well in conditions where the platform is still under development. Over a two-and-a-half-year time period, this study traced the development of a data platform in a revelatory case within the New Zealand tourism sector. It revealed five critical mass issues faced by the platform sponsor in phases of development that occur before platform launch: (i) attracting initial interest, (ii) aligning heterogenous goals, (iii) sustaining commitment to the project (iv), negotiating architecture design, and (v) sustaining commitment to implementation. These findings provide a foundation for problematizing critical mass theory and its boundary conditions in inter-organizational platform development

Preliminary assessment of the imaging capability of the YAP-(S)PET small animal scanner in neuroscience

The new and fully engineered version of the YAP–(S)PET small animal scanner has been tested at the University of Mainz for preliminary assessment of its imaging capability for studies related to neuropharmacology and psychiatry. The main feature of the scanner is the capability to combine PET and SPECT techniques. It allows the development of new and interesting protocols for the investigation of many biological phenomena, more effectively than with PET or SPECT modalities alone. The scanner is made up of four detector heads, each one composed of a 4 � 4c m 2 of YAlO3:Ce (or YAP:Ce) matrix, and has a field of view (FOV) of 4 cm axially � 4c m + transaxially. In PET mode, the volume resolution is less than 8 mm 3 and is nearly constant over the whole FOV, while the sensitivity is about 2%. The SPECT performance is not so good, due to the presence of the multi-hole lead collimator in front of each head. Nevertheless, the YAP–PET scanner offers excellent resolution and sensitivity for performing on the availability of D2-like dopamine receptors on mice and rats in both PET and SPECT modalities

Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients

Background: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Methods: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. Results: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. Conclusions: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

A review of the lumped element kinetic inductance detector

The Lumped Element Kinetic Inductance Detector (LEKID) was first proposed in 2007 as a solution for using kinetic inductance type detectors for sub-mm astronomy (450 - 200μm). Since then the LEKID has been demonstrated to have applications over a much wider range of wavelength. Examples of this have been 200μm detection of a cold blackbody and successful testing of a demonstration array operating at 2mm on the IRAM telescope in October 2009. Due to the combination of absorber and detector in a single element, the LEKID is an extremely simple detector to fabricate requiring only one deposition and etch step to produce an array of up to 1000 pixels multiplexed onto a single feedline. The LEKID is also a very compact detector making it ideal for producing arrays with high filling factors. The suitability of the LEKID for use in large arrays has prompted a return visit to the IRAM telescope with a dual band instrument in 2010. This presentation will review the progress to date of the LEKIDs development and outline design considerations for producing LEKIDs for future FIR astronomical instruments such as SPICA. Also reviewed will be possible applications for the LEKID outside sub-mm and mm astronomy

A continuous flow diffusion chamber study of sea salt particles acting as cloud nuclei: deliquescence and ice nucleation

Phase changes of sea salt particles alter their physical and chemical properties, which is significant for Earth’s chemistry and energy budget. In this study, continuous flow diffusion chamber is used to investigate deliquescence, homogeneous and heterogeneous ice nucleation between 242 K and 215 K, of four salts: pure NaCl, pure MgCl2, synthetic sea water salt, and salt distilled from sampled sea water. Anhydrous particles, aqueous droplets and ice particles were discriminated using a polarisation-sensitive optical particle counter coupled with a machine learning analysis technique. The measured onset deliquescence relative humidities agree with previous studies, where sea water salts deliquescence at lower humidities than pure NaCl. Deliquesced salt droplets homogenously freeze when the relative humidity reaches a sufficiently high value at temperatures below 233 K. From 224 K and below, deposition nucleation freezing on a fraction of NaCl particles was observed at humidities lower than the deliquescence relative humidity. At these low temperatures, otherwise unactivated salt particles deliquesced at the expected deliquescence point, followed by homogeneous freezing at temperatures as low as 215 K. Thus, the observed sea salt particles exhibit a triad of temperature-dependent behaviours. First, they act as cloud condensation particles (CCNs) > 233 K, second they can be homogeneous freezing nuclei (HFNs) < 233 K and finally they act as ice nucleating particles (INPs) for heterogeneous nucleation <224 K. Keywords: sea salt; deliquescence; homogeneous ice nucleation; heterogeneous ice nucleation; continuous flow diffusion chamberNational Science Foundation (U.S.) (Grant AGS-1461305)National Science Foundation (U.S.) (Grant AGS-1461347