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Abstract Organic solvents host the synthesis of high-value crystals used as pharmaceuticals and optical devices, among other applications. A knowledge gap persists on how replacing the hydrogen bonds and polar attraction that dominate aqueous environments with the weaker van der Waals forces affects the growth mechanism, including its defining feature, whether crystals grow classically or nonclassically. Here we demonstrate a rare dual growth mode of etioporphyrin I crystals, enabled by liquid precursors that associate with crystal surfaces to generate stacks of layers, which then grow laterally by incorporating solute molecules. Our findings reveal the precursors as mesoscopic solute-rich clusters, a unique phase favored by weak bonds such as those between organic solutes. The lateral spreading of the precursor-initiated stacks of layers crucially relies on abundant solute supply directly from the solution, bypassing diffusion along the crystal surface; the direct incorporation pathway may, again, be unique to organic solvents. Clusters that evolve to amorphous particles do not seamlessly integrate into crystal lattices. Crystals growing fast and mostly nonclassically at high supersaturations are not excessively strained. Our findings demonstrate that the weak interactions typical of organic systems promote nonclassical growth modes by supporting liquid precursors and enabling the spreading of multilayer stacks.

Niklas Kahr Rasmussen,1 Birgitte Berg,2 Anne Sia Louise Christiansen,3 Jesper Skov Neergaard,1 Gitte Ter-Borch,2 Emily A Hildebrand,4 Maya Gonczi,4 Thomas Sparre1 1Medical & Science Innovation, Novo Nordisk A/S, Søborg, Denmark; 2Clinical Operations, Novo Nordisk A/S, Søborg, Denmark; 3Biostatistics, Novo Nordisk A/S, Søborg, Denmark; 4Research Collective LLC, Tempe, AZ, USACorrespondence: Niklas Kahr Rasmussen, Medical & Science Innovation, Novo Nordisk A/S, Søborg, Denmark, Tel +45 3075 5040, Email NKHR@novonordisk.comIntroduction: Concizumab is a once-daily prophylactic treatment developed for patients with hemophilia A or B (HA/HB) with or without inhibitors. It is the first treatment for hemophilia patients to be delivered subcutaneously using a pre-filled, multi-dose pen-injector with a 4 mm, 32 G needle.Aim: To investigate patient and caregiver handling and preference for the concizumab pen-injector compared with current injection systems used to treat hemophilia.Methods: This preference and handling study was conducted in accordance with authority guidelines for approval of new devices and included adults and adolescents with HA/HB with or without inhibitors and caregivers currently administering factor replacement therapy or factor VIII mimetic (emicizumab) therapy. All participants underwent a training session, followed by a test session during which participants independently administered a single pen-injection into an injection pad or manikin. Time to train, time to prepare and inject, and number of complete independent injections handling the pen were assessed. Participants evaluated handling and preference via the Hemophilia Device Handling and Preference Assessment Questionnaire.Results: 80 participants (44 adults, 21 adolescents, 15 caregivers) currently using factor replacement therapy (n=41, 51%) or emicizumab (n=39, 49%) participated. Average training time and time to complete an injection were 7 min 49s and 1 min 21s. In total, 98% of independent complete injections were achieved at first attempt. 98% (n=78; 95% confidence interval [CI] 91– 100%) of participants assessed the pen-injector as either “easy” or “very easy” to use. 88% of participants preferred the pen-injector (n=70; 95% CI 78– 94%) over their current injection system, and 9% (n=7) reported “no preference”.Conclusion: Participants found the concizumab pen-injector easy to learn and easy to use and preferred it over their current injection systems.Plain Language Summary: People with hemophilia lack clotting factors that help stop bleeding after an injury. If left untreated, it can lead to life-threatening bleeding episodes. Treatment such as replacement therapy with clotting factors needs to be administered at regular intervals to prevent bleeding. The administration of intravenous (inside the vein) medication can be challenging due to the required skills, injection pain and availability of a good vein to inject into. Factor VIII mimetic therapy now allows people to inject medication under the skin (subcutaneously). However, using vials and syringes still poses challenges with the time to prepare and inject medication. Pen-injectors have been developed to address these challenges and provide additional benefits, including increased dose accuracy, portability, reduced discomfort, and less administration time. Concizumab is a medication developed for once-daily subcutaneous injection for people with hemophilia A or hemophilia B, with or without inhibitors, using a pen-injector. The objective of this preference and handling study was to understand patient and caregiver pen-injector handling experiences, and device preferences compared to their existing devices. In this study, most participants found it easy to learn to use the pen-injector. 98% of participants reported that the pen-injector was easy or very easy to use compared with their current device. 88% of participants reported a preference for the concizumab pen-injector over their current device. This shows that the pen-injector can easily and effectively be used to inject concizumab, providing more control and independence in patients’ treatment while reducing the burden caused by intravenous modes of administration.Keywords: concizumab, pen-injector, subcutaneous, preference and handling study, questionnaire

ObjectivesThe purpose of the systematic review was to synthesize literature on eating disorders (ED) and non-interpersonal traumatic events (NTE) and consolidate the reported prevalence of NTE in patients with an ED.MethodsThe literature search was performed in Embase, PsycInfo, and PubMed. The keywords in the search were “eating disorder,” “trauma” and “non-interpersonal,” using index-terms and free-search keywords related to NTE and ED. The PRISMA guidelines were followed. Relevant studies were screened using Rayyan.ResultsOf the 16 studies included in the quantitative synthesis, five overall types of NTE were identified: accidents, illness, injury, natural disaster and war. Findings provided tentative evidence for illness and injury being more prevalent in patients suffering from an ED compared to controls. The remaining subtypes of NTE did not show a higher prevalence in patients with an ED when compared to controls. Findings also suggest that those with binge/purge subtype of anorexia nervosa (AN) had a higher prevalence of non-interpersonal traumatic events compared to the restrictive subtype of AN.DiscussionThis systematic review provided a clear synthesis of previous findings related to NTE among patients with an ED. Noteworthy, is that many studies do not take into account if the trauma happened prior or after to ED onset, which may affect the association. Furthermore, the body of research on NTE in patients with ED is exceedingly limited, and more research is needed.

IntroductionSARS-CoV-2 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to comprehensively assess symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe COVID-19 infection.MethodsThis prospective registry included patients with PCR-confirmed COVID-19 infection requiring hospitalization. Follow-up approximately 6 months post discharge comprised a detailed patient history, clinical examination, transthoracic echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a laboratory panel. At the time of the second follow-up visit at 18 months, patients without pathologic findings during the first study visit were contacted by phone to inquire about the course of their symptoms. In all other patients all initial examinations were repeated.ResultsTwo hundred Patients, who were hospitalized for COVID-19, were contacted by phone and were recruited for the study. Due to dropouts the second study visit was performed in 170 patients. A comparison between the two study visits at 6 and 18 months post discharge showed the following results: Six months after discharge, 73% and 18 months after discharge 52% fulfilled the criteria for Long COVID with fatigue being the most common symptom (49%). Echocardiography at 6 months post discharge showed an impaired left ventricular function in 8% of which 80% returned to normal. Six months post discharge, cMRI revealed pericardial effusion in 17% which resolved in 47% of the 15 patients who underwent a control cMRI. Signs of peri- or myocarditis were present in 5% of the patients and were resolved in all 4 patients who attended control studies. At 6 months, chest CT scans identified post-infectious residues in 24%. In the 25 repeated chest CT scans 20% showed full recovery. Length of in-hospital stay was identified as a significant predictor for persisting Long COVID (95% CI: 1.005–1.12, p = 0.03).ConclusionComparing 6 to 18 months, the prevalence of Long COVID decreased over time, but a high symptom burden remained. Structural and functional abnormalities were less frequent than the portrayed symptoms, and it thus remains a challenge to substantiate the symptoms.

Abstract Background Controlling malaria-transmitting Anopheles mosquitoes with pyrethroid insecticides is becoming increasingly challenging because of widespread resistance amongst vector populations. The development of new insecticides and insecticidal formulations is time consuming and costly, however. A more active crystalline form of deltamethrin, prepared by heating the commercial crystalline form, previously was reported to be 12-times faster acting against susceptible North American Anopheles quadrimaculatus mosquitoes. Herein the potential for heat-activated deltamethrin dispersed on chalk to overcome various resistance mechanisms amongst five West African Anopheles strains is investigated, and its long-term sustained lethality evaluated. Methods The more active deltamethrin form was generated in a commercial dust containing deltamethrin by heating the material as purchased. Tarsal contact bioassays were conducted to investigate its efficacy, potency, and speed of action against resistant Anopheles populations compared to the commercially available form of deltamethrin dust. Results In all cases, D-Fense Dust heated to generate the more active form of deltamethrin was substantially more effective than the commercially available formulation. 100% of both Banfora M and Kisumu populations were knocked down 10 min post-exposure with no recovery afterwards. Gaoua-ara and Tiefora strains exhibited 100% knockdown within 15 min, and the VK7 2014 strain exhibited 100% knockdown within 20 min. In all cases, 100% mortality was observed 24 h post-exposure. Conversely, the commercial formulation (unheated) resulted in less than 4% mortality amongst VK7 2014, Banfora, and Gaoua-ara populations by 24 h, and Tiefora and Kisumu mosquitoes experienced 14 and 47% mortality by 24 h, respectively. The heat-activated dust maintained comparable efficacy 13 months after heating. Conclusions The heat-activated form of commercial deltamethrin D-Fense Dust outperformed the material as purchased, dramatically increasing efficacy against all tested pyrethroid-resistant strains. This increase in lethality was retained for 13 months of storage under ambient conditions in the laboratory. Higher energy forms of commonly used insecticides may be employed to overcome various resistance mechanisms seen in African Anopheles mosquitoes through more rapid uptake of insecticide molecules from their respective solid surfaces. That is, resistant mosquitoes can be killed with an insecticide to which they are resistant without altering the molecular composition of the insecticide.

Multiplex sampling, so far mainly used as a tool for S/N ratio improvement in spectroscopic applications and separation techniques, has been investigated here for its potential suitability for time-resolved monitoring where chromatograms of transient signals are recorded at intervals much shorter than the chromatographic runtime. Different designs of multiplex sample introduction were developed and utilized to analyze lithium-ion battery degradation products under normal or abuse conditions to achieve fast and efficient sample introduction. After comprehensive optimization, measurements were performed on two different GC systems, with either barrier discharge ionization detection (BID) or mass spectrometric detection (MS). Three different injector designs were examined, and modifications in the pertinent hardware components and operational conditions used. The shortest achievable sample introduction time was 50 ms with an interval of 6 s. Relative standard deviations were lower than 4% and 10% for the intra- and inter-day repeatability, respectively. The sample introduction system and column head pressure had to be carefully controlled, as this parameter most critically affects the amount of sample introduced and, thus, detector response. The newly developed sample introduction system was successfully used to monitor volatile degradation products of lithium-ion batteries and demonstrated concentration changes over the course of time of the degradation products (e.g., fluoroethane, acetaldehyde and ethane), as well as for solvents from the battery electrolyte like ethyl carbonate.

Many roles of human platelets in health and disease are linked to their ability to transport and secrete a variety of small molecules and proteins carried in dense (δ-) and α-granules. Determination of granule number and content is important for diagnosis of platelet disorders and for studies of platelet structure, function, and development. We have optimized methods for detection and localization of platelet proteins via antibody and lectin staining, imaging via structured illumination laser fluorescence microscopy (SIM), and three-dimension (3D) image analysis. The methods were validated via comparison with published studies based on electron microscopy and high-resolution fluorescence microscopy. The α-granule cargo proteins thrombospondin-1 (TSP1), osteonectin (SPARC), fibrinogen (FGN), and Von Willebrand factor (VWF) were localized within the granule lumen, as was the proteoglycan serglycin (SRGN). Colocalization analysis indicates that staining with fluorescently labeled wheat germ agglutinin (WGA) allows detection of α-granules as effectively as immunostaining for cargo proteins, with the advantage of not requiring antibodies. RAB27B was observed to be concentrated at dense granules, allowing them to be counted via visual scoring and object analysis. We present a workflow for counting dense and α-granules via object analysis of 3D SIM images of platelets stained for RAB27B and with WGA. Abbreviation: SIM: structured illumination microscopy; WGA: wheat germ agglutinin; FGN: fibrinogen; TSP1: thrombospondin 1; ER: endoplasmic reticulum

There are about 100 chemical elements, and 200 space groups, rounding to the nearest hundreds. The elements, by virtue of the iconic periodic table, which hangs in schoolrooms worldwide, are part of our common culture. Few on the outside of solid-state science and discrete mathematics know of the remarkable enumeration of the space groups and how they organize solids, the chemical elements included, that can be conformed to translationally periodic lattices in three dimensions. Perhaps the comparative inaccessibility of space groups to non-specialists can be attributed to the absence of a single chart that captures and organizes the space groups in a glance, as does the periodic table for the chemical elements? Here is designed a periodic-like table of the space groups. The symmorphic space groups are organized as the coordinates of two non-linear, non-orthogonal axes that capture the point group symmetry and the order of the group, the multiplicity of general positions. The related non-symmorphic groups are treated as `isotopes' of the symmorphic groups and are enumerated with a subscript. The intent is to inspire better designs and to bring the crystallographic space groups to the attention of a wider audience.

The global Covid 19-pandemic led to many challenges for higher education (HE) teachers. However, it also provided an opportunity to not only re-evaluate a previously unquestioned teaching culture, but also to fundamentally question the capabilities of HE institutions and teachers to implement digitally supported education at the organizational, teaching, and learning levels. In this study, we analyzed data from 1,339 HE teachers’ conclusions for post-pandemic teaching terms of instructional course quality. Our findings shed light on HE teachers’ mindsets toward traditional face-to-face and online teaching, as well as (im)probable changes in academic teaching culture. Our results offer a “bottom-up” basis for recommendations on how institutions can support their faculty for digital transformations in HE based on teachers’ expertise and perceptions of the advantages and hindrances of HE online teaching.

Optically anisotropic materials were produced via colloidal lithography and characterized using scanning electronic microscopy (SEM), confocal microscopy, and polarimetry. A compact hexagonal array mask composed of silica sub-micron particles was fabricated via the Langmuir–Blodgett self-assembly technique. Subsequently, the mask pattern was transferred onto monocrystalline silicon and commercial glass substrates using ion beam etching in a vacuum. Varying the azimuthal angle while etching at oblique incidence carved screw-like shaped pillars into the substrates, resulting in heterochiral structures depending on the azimuthal angle direction. To enhance the material’s optical properties through plasmon resonance, gold films were deposited onto the pillars. Polarimetric measurements were realized at normal and oblique incidences, showing that the etching directions have a clear influence on the value of the linear birefringence and linear dichroism. The polarimetric properties, especially the chiroptical responses, increased with the increase in the angle of incidence.

Introduction Psychology students at universities in Denmark and worldwide often receive relatively little clinical training, even though such training is crucial to job performance after graduation. Training common psychotherapeutic skills, such as being empathic and facilitating the therapeutic alliance, is critical since these skills are related to psychotherapy outcomes. In this study, a deliberate practice-based approach to student training will be compared with theoretical teaching. The main hypothesis is that deliberate practice training will result in a larger improvement in students’ observer-rated interpersonal skills.Methods and analysis The TRaining of graduate students In general Psychotherapeutic Skills study has a double-centre, randomised, assessor-blinded, two-way crossover study design. About 200 graduate students from two Danish universities will be randomised into two groups, (a) deliberate practice training of common psychotherapeutic skills using role-play and Skillsetter, an online skill-building system with therapy videos or (b) theoretical teaching. Group a will first receive the experimental condition, followed by the control condition, while group b will receive the conditions in reverse order. Each condition consists of 15 hours of classroom participation and homework. The primary outcome is facilitative interpersonal skills—observer. Secondary outcomes include the facilitative interpersonal skills—self-report, the Counselor Activity Self-Efficacy Scales and the Interpersonal Reactivity Index. Outcomes will be measured at baseline (week 0), after the first condition (week 5; before the crossover, reflecting true randomisation) and after both conditions (week 10). Main outcome analyses will be performed at week 5. Several predictors of the effect of deliberate practice will be explored.Ethics and dissemination Ethical approval from university ethics boards has been obtained. All participants will be asked to provide informed consent before participation. Once completed, the study can potentially transform the training of psychotherapy in graduate education, which, ultimately, may positively influence psychotherapy outcomes (IP-IRB / 03092021).Trial registration number NCT05164497.

Abstract Background Severe hemophilia A (SHA) patients vary in severity of bleeding, arthropathy, and requirements for replacement factor VIII (FVIII). Baseline hemostatic activity assays using calibrated automated thrombography (CAT) and thromboelastography (TEG) may offer insights into the physiological basis of clinical heterogeneity. Objectives Use CAT and TEG to measure baseline hemostatic activity in a cohort of 30 pediatric SHA patients with available clinical data. Determine effect of contact activation inhibition with corn trypsin inhibitor (CTI). Assess heterogeneity among patients for baseline hemostatic activity and examine correlations between assay results and clinical parameters including FVIII dosing regimen, von Willebrand factor level, and Pettersson arthropathy score. Methods SHA blood after FVIII washout was subjected to TEG, and platelet‐rich (PRP) and platelet‐poor plasma was used for CAT assays. Varying concentrations of tissue factor (TF) were used. Statistical analysis examined relationships between assay results, and clinical parameters. Results CTI treatment was required to obtain TEG and CAT results representative of baseline hemostatic activity. Weak activity was observed in assays with low TF concentrations (0.5–2 pM), and most but not all samples approached normal activity levels at high TF concentrations (10–20 pM). A significant positive correlation was observed between results of TEG and CAT‐PRP assays. Correlations were not detected between hemostatic assay results and clinical parameters. Conclusions In vitro hemostatic assay results of samples containing platelets showed concordance. Assay results were not predictive of FVIII requirements or correlated with other clinical parameters. SHA patient heterogeneity is influenced by factors other than baseline hemostatic activity.

Abstract Aims Cardiac resynchronization therapy (CRT) has become an important therapy in patients with heart failure with reduced left ventricular ejection fraction (LVEF). The effect of diabetes on long‐term outcome in these patients is controversial. We assessed the effect of diabetes on long‐term outcome in CRT patients and investigated the role of diabetes in ischaemic and non‐ischaemic cardiomyopathy. Methods and results All patients undergoing CRT implantation at our institution between November 2000 and January 2015 were enrolled. The study endpoints were (i) a composite of ventricular assist device (VAD) implantation, heart transplantation, or all‐cause mortality; and (ii) reverse remodelling (improvement of LVEF ≥ 10% or reduction of left ventricular end‐systolic volume ≥ 15%). Median follow‐up of the 418 patients (age 64.6 ± 11.6 years, 22.5% female, 25.1% diabetes) was 4.8 years [inter‐quartile range: 2.8;7.4]. Diabetic patients had an increased risk to reach the composite endpoint [adjusted hazard ratio (aHR) 1.48 [95% CI 1.12–2.16], P = 0.041]. Other factors associated with an increased risk to reach the composite endpoint were a lower body mass index or baseline LVEF (aHR 0.95 [0.91; 0.98] and 0.97 [0.95; 0.99], P

A molecular genetic and morphometric investigation revealed the supposedly widespread Caribbean and Western Atlantic intertidal oribatid mite species Fortuynia atlantica to comprise at least two different species. Although there are no distinct morphological differences separating these taxa, COI and 18S sequence divergence data, as well as different species delimitation analyses, clearly identify the two species. Fortuynia atlantica is distributed in the northern Caribbean and the Western Atlantic and the new Fortuynia antillea sp. nov. is presently endemic to Barbados. Vicariance is supposed to be responsible for their genetic diversification and stabilizing selection caused by the extreme intertidal environment is suggested to be the reason for the found morphological stasis. The genetic structure of Fortuynia atlantica indicates that Bermudian populations are derived from the northern Caribbean and thus support the theory of dispersal by drifting on the Gulf Stream. Haplotype network data suggest that Bermudian and Bahamian populations were largely shaped by colonization, expansion and extinction events caused by dramatic sea level changes during the Pleistocene. A preliminary phylogenetic analysis based on 18S gene sequences indicates that the globally distributed genus Fortuynia may be a monophyletic group, whereas Caribbean and Western Atlantic members are distinctly separated from the Indo-Pacific and Western Pacific species.

A molecular genetic and morphometric investigation revealed the supposedly widespread Caribbean and Western Atlantic intertidal oribatid mite species Fortuynia atlantica to comprise at least two different species. Although there are no distinct morphological differences separating these taxa, COI and 18S sequence divergence data, as well as different species delimitation analyses, clearly identify the two species. Fortuynia atlantica is distributed in the northern Caribbean and the Western Atlantic and the new Fortuynia antillea sp. nov. is presently endemic to Barbados. Vicariance is supposed to be responsible for their genetic diversification and stabilizing selection caused by the extreme intertidal environment is suggested to be the reason for the found morphological stasis. The genetic structure of Fortuynia atlantica indicates that Bermudian populations are derived from the northern Caribbean and thus support the theory of dispersal by drifting on the Gulf Stream. Haplotype network data suggest that Bermudian and Bahamian populations were largely shaped by colonization, expansion and extinction events caused by dramatic sea level changes during the Pleistocene. A preliminary phylogenetic analysis based on 18S gene sequences indicates that the globally distributed genus Fortuynia may be a monophyletic group, whereas Caribbean and Western Atlantic members are distinctly separated from the Indo-Pacific and Western Pacific species.

The summer semester had just begun at Austrian and German universities when Covid-19 was declared a global pandemic by the World Health Organization. Thus, in March 2020, all universities closed their campuses, switching to distance learning within the span of about a single day. How did lecturers handle the situation? Were they still able to turn the situation into a positive one? What were the main obstacles with this difficult situation, and where there conditions which helped them to overcome the new challenges? These are research questions of the present survey with a sample of 1,152 lecturers at universities in Austria and Germany. The survey focuses on the lecturers’ appraisals of the novel situation as challenging or threatful. These appraisals are important for approaching a situation or shying away from it. However, how well a person adjusts to a novel situation is also influenced by personal and environmental resources which help to overcome the situation. The present survey focused on four possible sources of influence: internal assessments of the situation determining it to be threatening and/or challenging, personal resources, attitudes, and support by the organization. It was investigated to which degree these sources of influence could contribute to the lecturers’ satisfaction (or dissatisfaction) with their teaching processes. A multiple regression with three criterion variables describing university lecturers’ perceived satisfaction with distance teaching was carried out. Predictor variables were the lecturers’ appraisals of challenge and threat, perceived support by the university and sense of belonging to the university, temporal resources, proficiency in using digital technologies, length of teaching experience, and gender. Lecturers were mostly satisfied with their teaching activities. Together with the perception of a low threat potential, challenge appraisals contributed strongest to satisfaction. In comparison, assessments of actual personal resources, skills in the use of digital technologies, teaching experience, and temporal resources were important but contributed less to satisfaction than challenge appraisals. It seems that lecturers were only able to use these resources when the technological resources were available and when the lecturers were confident in their technical abilities.

Editorial independence is a bedrock principle of academic publishing. The growing domination of academic publishing by large, for-profit corporations threatens this independence. There is alarming evidence that large companies too often serve their own business interests and those of powerful clients rather than serving the scientific community and the general public. This evidence includes the publication of infelicitous commercial science and concealing scientific misconduct. We present two case studies in which the UK-based publisher Taylor & Francis interfered in the editorial process by blocking publication of legitimate criticism that had been reviewed and approved for publication by its specialized editors. The integrity of science depends in part on the transparency and intellectual honesty of all stakeholders. The widely-acknowledged inadequacies of English libel law are reviewed as context for some of Taylor & Francis’s fearful decisions.

Real-time monitoring is essential for understanding and precisely controlling of growth of two-dimensional transition metal dichalcogenide (2D TMDC) materials. However, it is very challenging to carry out such studies during chemical vapor deposition (CVD). Here, we report the first, real time, in situ study of the CVD growth of 2D TMDCs. More specifically, the CVD growth of a molybdenum disulfide (MoS2) monolayer on sapphire substrates has been monitored in situ using differential transmittance spectroscopy (DTS). The growth of the MoS2 monolayer can be precisely followed by observation of the evolution of the characteristic optical features. Consequently, a strong correlation between the growth rate of the MoS2 monolayer and the temperature distribution in the CVD reactor has been revealed. Our results demonstrate the great potential of real time, in situ optical spectroscopy to assist the precisely controlled growth of 2D semiconductor materials.

BackgroundAs a daily point measurement, basal body temperature (BBT) might not be able to capture the temperature shift in the menstrual cycle because a single temperature measurement is present on the sliding scale of the circadian rhythm. Wrist skin temperature measured continuously during sleep has the potential to overcome this limitation. ObjectiveThis study compares the diagnostic accuracy of these two temperatures for detecting ovulation and to investigate the correlation and agreement between these two temperatures in describing thermal changes in menstrual cycles. MethodsThis prospective study included 193 cycles (170 ovulatory and 23 anovulatory) collected from 57 healthy women. Participants wore a wearable device (Ava Fertility Tracker bracelet 2.0) that continuously measured the wrist skin temperature during sleep. Daily BBT was measured orally and immediately upon waking up using a computerized fertility tracker with a digital thermometer (Lady-Comp). An at-home luteinizing hormone test was used as the reference standard for ovulation. The diagnostic accuracy of using at least one temperature shift detected by the two temperatures in detecting ovulation was evaluated. For ovulatory cycles, repeated measures correlation was used to examine the correlation between the two temperatures, and mixed effect models were used to determine the agreement between the two temperature curves at different menstrual phases. ResultsWrist skin temperature was more sensitive than BBT (sensitivity 0.62 vs 0.23; P

The anthropologist and acclaimed essayist, Loren Eiseley, in the midst of recounting a vision in the conclusion of a draft of a 1960 composition, “Creativity and Modern Science,” invoked Charles Darwin as the essay’s animating spirit. Eiseley modified his draft the next year and published it in no less than three of his subsequent books. The most striking differences between his draft and published texts is the substitution of Darwin in the final moments of the narrative with Francis Bacon, a barrister and philosopher who died nearly two centuries before the famous biologist was born. Here, is crafted a rationale for this unlikely switch, to the extent that the intent of another can be uncovered, by closely reading Eiseley’s psychologically charged work. Eiseley’s own struggles as both a scientist and an artist, identities respectively epitomized by Darwin and Bacon, reveal how and why the writer permitted his foremost heroes to be substituted, one for the other.

The active forms of contact insecticides used for combatting mosquito-borne infectious diseases are typically crystalline solids. Numerous molecular crystals are polymorphic, crystallizing in several solid forms characterized by different physicochemical properties, including bioavailability. Our laboratory recently found that the activity of crystalline contact insecticides is inversely dependent on the thermodynamic stability of their polymorphs, suggesting that efficacy can be enhanced by the manipulation of the solid-state structure. This paper argues that crystallography should be central to the development of contact insecticides, particularly because their efficacy continues to be compromised by insecticide resistance, especially among Anopheles mosquito populations that spread malaria. Although insecticidal compounds with new modes of action have been introduced to overcome resistance, new insecticides are expensive to develop and implement. The repurposing of existing chemical agents in metastable, more active crystalline forms provides an inexpensive and efficient method for ‘evergreening’ compounds whose risks are already well-established. We report herein seven new single-crystal structures of insecticides used for controlling infectious disease vectors. The structures reported herein include pyrethroid insecticides recommended by the WHO for indoor residual spraying (IRS)-bifenthrin, β-cyfluthrin, etofenprox, α-cypermethrin, and λ-cyhalothrin as well as the neonicotinoid insecticide thiacloprid.

Rolling element bearing faults significantly contribute to overall machine failures, which demand different strategies for condition monitoring and failure detection. Recent advancements in machine learning even further expedite the quest to improve accuracy in fault detection for economic purposes by minimizing scheduled maintenance. Challenging tasks, such as the gathering of high quality data to explicitly train an algorithm, still persist and are limited in terms of the availability of historical data. In addition, failure data from measurements are typically valid only for the particular machinery components and their settings. In this study, 3D multi-body simulations of a roller bearing with different faults have been conducted to create a variety of synthetic training data for a deep learning convolutional neural network (CNN) and, hence, to address these challenges. The vibration data from the simulation are superimposed with noise collected from the measurement of a healthy bearing and are subsequently converted into a 2D image via wavelet transformation before being fed into the CNN for training. Measurements of damaged bearings are used to validate the algorithm’s performance.

Few would expect women to feature often in the literature on minerology from the 15th through the 19th centuries, the recorded history of science being what it is. Among the approximately 1500 scholars in a massive catalogue of authors of mineralogy texts from 1439 to 1919 complied by the independent scholar, Curtis P. Schuh, we count six women as primary entries and three others discussed secondarily. From the documents that Schuh left behind before his death, our database for this investigation, women wrote approximately 0.5% of the texts described. Only very unusual circumstances supported the life of a woman devoted to crystals in centuries past.

Homozygosity/compound heterozygosity for loss of function mutations in neurobeachin-like 2 (NBEAL2) is causative for Gray platelet syndrome (GPS; MIM #139090), characterized by thrombocytopenia and large platelets lacking α-granules and cargo. Most GPS-associated NBEAL2 mutations generate nonsense codons; frameshifts causing premature translation termination and/or changes in mRNA splicing have also been observed. Data regarding NBEAL2 protein expression in GPS patients is limited. We observed absence of NBEAL2 in platelets from GPS patients with 3 different genotypes, and reduced/truncated platelet NBEAL2 has been reported for others. GPS is commonly associated with mild bleeding, but lifethreatening bleeding has been reported in some cases. A common long-term complication in GPS patients is myelofibrosis; splenomegaly is less common but sometimes of sufficient severity to merit splenectomy. Like GPS patients, mice lacking NBEAL2 expression exhibit macrothrombocytopenia, deficiency of platelet α-granules, splenomegaly, myelofibrosis, impaired platelet function and abnormalities in megakaryocyte development. Animal studies have also reported impaired platelet function in vivo using laser injury and thrombo-inflammation models. NBEAL2 is a large gene with 54 exons, and several putative functional domains have been identified in NBEAL2, including PH (pleckstrin homology) and BEACH (beige and Chediak-Higashi) domains shared with other members of a protein family that includes LYST and LRBA, also expressed by hematopoietic cells. Potential NBEAL2-interacting proteins have recently been identified, and it is expected that current and future efforts will reveal the cellular mechanisms by which NBEAL2 facilitates platelet development and supports hemostatic function.

Coating conducting polymers onto active cathode materials has been proven to mitigate issues at high current densities stemming from the limited conducting abilities of the metal-oxides. In the present study, a carbon coating was applied onto nickel-rich NMC622 via polymerisation of furfuryl alcohol, followed by calcination, for the first time. The formation of a uniform amorphous carbon layer was observed with scanning- and transmission-electron microscopy (SEM and TEM) and X-ray photoelectron spectroscopy (XPS). The stability of the coated active material was confirmed and the electrochemical behaviour as well as the cycling stability was evaluated. The impact of the heat treatment on the electrochemical performance was studied systematically and was shown to improve cycling and high current performance alike. In-depth investigations of polymer coated samples show that the improved performance can be correlated with the calcination temperatures. In particular, a heat treatment at 400 °C leads to enhanced reversibility and capacity retention even after 400 cycles. At 10C, the discharge capacity for carbon coated NMC increases by nearly 50% compared to uncoated samples. This study clearly shows for the first time the synergetic effects of a furfuryl polymer coating and subsequent calcination leading to improved electrochemical performance of nickel-rich NMC622.

ARPC1B is a component of the actin-related protein 2/3 complex (Arp2/3), which is required for actin filament branching. Kahret al. show that ARPC1B deficiency in humans is associated with severe multisystem disease that includes platelet abnormalities, eosinophilia, eczema and other indicators of immune disease.

Platelets are critical to hemostasis and thrombosis. Upon detecting injury, platelets show a range of responses including the release of protein cargo from α-granules. This cargo is synthesized by platelet precursor megakaryocytes or endocytosed by megakaryocytes and/or platelets. Insights into α-granule biogenesis have come from studies of hereditary conditions where these granules are immature, deficient or absent. Studies of Arthrogryposis, Renal dysfunction, and Cholestasis (ARC) syndrome identified the first proteins essential to α-granule biogenesis: VPS33B and VPS16B. VPS33B and VPS16B form a complex, and in the absence of either, platelets lack α-granules and the granule-specific membrane protein P-selectin. Gray Platelet Syndrome (GPS) platelets also lack conventionally recognizable α-granules, although P-selectin containing structures are present. GPS arises from mutations affecting NBEAL2. The GPS phenotype is more benign than ARC syndrome, but it can cause life-threatening bleeding, progressive thrombocytopenia, and myelofibrosis. We review the essential roles of VPS33B, VPS16B, and NBEAL2 in α-granule development. We also examine the existing data on their mechanisms of action, where many details remain poorly understood. VPS33B and VPS16B are ubiquitously expressed and ARC syndrome is a multisystem disorder that causes lethality early in life. Thus, VPS33B and VPS16B are clearly involved in other processes besides α-granule biogenesis. Studies of their involvement in vesicular trafficking and protein interactions are reviewed to gain insights into their roles in α-granule formation. NBEAL2 mutations primarily affect megakaryocytes and platelets, and while little is known about NBEAL2 function some insights can be gained from studies of related proteins, such as LYST.

Atypical hemolytic uremic syndrome is a thrombotic microangiopathy, which is linked to hereditary or autoimmune defects in complement activators or regulators present in blood and on vascular endothelial cells. Acute thrombotic microangiopathy episodes are typically preceded by infections, which by themselves would not be expected to manifest HUS. Thus, it is possible that the host immune response contributes to the precipitation of aHUS. However, the mechanisms involved are not fully understood. We hypothesized that neutrophils trigger aHUS via initiating platelet aggregate formation on complement-activated endothelial cells. Methods: We investigated neutrophil adhesion to complement-activated endothelial cells under static and flow conditions in vitro and ex vivo. Results: Our results show that complement activation on endothelial cells promotes neutrophil adhesion, which is significantly reduced when the complement terminal pathway is blocked. When neutrophils and platelets are perfused simultaneously, neutrophils adhering to endothelial cells also induce the formation of platelet-neutrophil aggregates on these cells. Sera from patients with aHUS recapitulated these results. Discussion: Therefore, our findings of (i) neutrophils adhering to complement-activated endothelial cells, (ii) the formation of neutrophil-platelet aggregates on endothelial cells, and (iii) the ability of aHUS serum to induce similar effects identify a possible role for neutrophils in aHUS manifestation.

In der vorliegenden Evaluationsstudie wurden Studierende und Lehrende einer österreichischen Universität befragt, in welchen Bereichen der Lehre sich Studierende eine stärkere Flexibilisierung wünschen und inwieweit sich diese Wünsche von der Einschätzung Lehrender unterscheiden. Die Ergebnisse zeigen, dass Studierende und Lehrende in ihren Präferenzen zur Lehrveranstaltungsgestaltung zum großen Teil übereinstimmen, sich aber auch in einzelnen Bereichen unterscheiden. Insbesondere hinsichtlich einzelner Aspekte von Zeit, Inhalt, Lernressourcen und Support, Beurteilung und Bereitstellung schätzen Studierende Flexibilität bedeutsamer ein als Lehrende. Es zeigen sich hier bedeutsame statistische Effekte.

Most research universities have concrete policies for navigating the conflicts of interest of faculty members. Policies that might constrain university administrators acting on behalf of their schools, so-called institutional conflicts of interest, are absent or poorly developed at most places that could benefit from them. Researchers have argued for the illustration of institutional conflicts as a foundation for policy development. Here, we show the failure of research accountability when a faculty member made massive gifts to a leading American public research university, the University of Washington in Seattle, thereby creating allegiances that undermined commitments to academic values. Correspondence, some from thousands of pages acquired through the Washington State Public Records Act, show faculty colleagues, department chairs, deans, a provost, presidents, and the Board of Regents soliciting and accepting the donor's money but not sufficiently guarding the integrity of science when that was required. These records offer a rare look inside a university scientific misconduct investigation, a process typically shrouded in secrecy under the guise of confidentiality. They amount to a forensic analysis of what can go wrong with science at the nexus of a secret history of misconduct, spectacularly ambitious science, and large donations. The inabilities of federal and state authorities to reckon with institutional conflicts of interest are highlighted. The collective inaction can be understood within Lessig’s framework of institutional corruption. The failings described herein are metaphorical holes in the safety net intended to protect the integrity of American science, a shared practice that is under increasing strain. All public records are available from the authors upon request. Those cited here are included in an appendix posted by the journal.

Editorial independence is a bedrock principle of academic publishing. The growing domination of academic publishing by large, for-profit corporations threatens this independence. There is alarming evidence that large companies too often serve their own business interests and those of powerful clients rather than serving the scientific community and the general public. This evidence includes the publication of infelicitous commercial science and concealing scientific misconduct. We present two case studies in which the UK-based publisher Taylor & Francis interfered in the editorial process by blocking publication of legitimate criticism that had been reviewed and approved for publication by its specialized editors. The integrity of science depends in part on the transparency and intellectual honesty of all stakeholders. The widely-acknowledged inadequacies of English libel law are reviewed as context for some of Taylor & Francis’s fearful decisions.

In contrast to most common gene delivery techniques, lentiviral vectors allow targeting of almost any mammalian cell type, even non-dividing cells, and they stably integrate in the genome. Therefore, these vectors are a very powerful tool for biomedical research. Here we report the generation of a versatile new set of 22 lentiviral vectors with broad applicability in multiple research areas. In contrast to previous systems, our platform provides a choice between constitutive and/or conditional expression and six different C-terminal fusions. Furthermore, two compatible selection markers enable the easy derivation of stable cell lines co-expressing differently tagged transgenes in a constitutive or inducible manner. We show that all of the vector features are functional and that they contribute to transgene overexpression in proof-of-principle experiments.

In der Praxis wird zumeist angenommen, dass die Ergebnisse in einem Aufnahmeverfahren individuelle Unterschiede in den zu erfassenden Fähigkeiten fair messen. Der vorliegende Beitrag gibt einen Überblick über Modelle zur Fairness von Aufnahmeverfahren und deren Überprüfung in der Praxis anhand von Beispielen zum Aufnahmeverfahren für Medizinische Studiengänge in Österreich (MedAT). Der Beitrag arbeitet zudem auch den engen Zusammenhang zwischen Fairness und anderen Gütekriterien heraus und veranschaulicht die Vorteile einer stark theoriegeleiteten automatischen Itemgenerierung (AIG), um auf die erhöhten Qualitätsanforderungen bei modernen Aufnahmeverfahren reagieren zu können.

Arrhythmogenic cardiomyopathy (AC) is a rare mostly hereditary disease, in which fibro-fatty tissue replaces cardiomyocytes. Typically, the first alterations of the disease can be encountered in the epicardium of the right ventricle in adolescent patients. From there, the disease usually progresses over time. Besides the development of heart failure, the clinical significance of the disease is determined by the predisposition to potentially lethal ventricular arrhythmias. Hence, a majority of patients with AC require an implantable cardioverter-defibrillator (ICD) to be protected from sudden cardiac death. A recently developed alternative to transvenous systems are subcutaneous ICDs (S-ICD), associated with a lower risk of device-related complications such as endocarditis since no foreign material is implanted within the heart and vascular system. In this report, we describe and discuss our experience with the implantation of a S-ICD in a patient with AC, who had low QRS voltage and persistent atrial fibrillation precluding successful S-ICD implantation, as well as the challenges encountered during subsequent transvenous lead implantation.

Ultrasound exams need skilled examiners, and simulation-based training could provide standardized and safe skill training. This study aims to give an overview of different types of virtual-reality simulators for use in abdominal diagnostic ultrasound training in radiology. Fifteen specialized radiologists and radiological residents were presented with two similar cases on four different simulators for abdominal ultrasound training. A feedback sheet for each individual simulator and for an overall comparison was filled out by all participants. All means of scores were compared, and simulators were ranked from least to most favorable. One simulator was ranked most favorable in seven out of nine questions, but none of the mean scores had statistically significant differences. All simulators were recommended for training radiologists, and all simulators were perceived to benefit trainees more than experienced ultra-sonographers.

Accurate knowledge of the spatial magnetic field distribution is necessary when measuring field gradients. Therefore, a MEMS magnetic field gradiometer is reported, consisting of two identical, but independent laterally oscillating masses on a single chip. The sensor is actuated by Lorentz force and read out by modulation of the light flux passing through stationary and moving arrays of the chip. This optical readout decouples the transducer from the electronic components. Both phase and intensity are recorded which reveals information about the uniformity of the magnetic field. The magnetic flux density is measured simultaneously at two points in space and the field gradient is evaluated locally. The sensor was characterised at ambient pressure by performing frequency and magnitude response measurements with coil and various different permanent magnet arrangements, resulting in a responsivity of 35.67 V/T and detection limit of 3.07 µT/ Hz (@ 83 Hz ENBW). The sensor is compact, offers a large dynamic measurement range and can be of low-cost by using conventional MEMS batch fabrication technology.

Neutrophils deposit antimicrobial proteins such as myeloperoxidase and proteases on chromatin, which they release as neutrophil extracellular traps (NETs). Neutrophils also carry key components of the complement alternative pathway (AP) such as properdin or complement factor P (CFP), complement factor B (CFB) and C3. However, the contribution of these complement components and complement activation during NET formation in the presence and absence of bacteria is poorly understood. We studied complement activation on NETs and a Gram-negative opportunistic bacterial pathogen Pseudomonas aeruginosa (PA01, PAKwt, PAKgfp). Here we show that anaphylatoxin C5a, formyl-Methionyl-Leucyl-Phenylalanine (fMLP), and phorbol myristate acetate (PMA) that activates NADPH oxidase induce the release of CFP, CFB and C3 from neutrophils. In response to PMA or P. aeruginosa, neutrophils secrete CFP, deposit it on NETs and bacteria, and induce the formation of terminal complement complexes (C5b-9). A blocking anti-CFP antibody inhibited AP-mediated but not non-AP-mediated complement activation on NETs and P. aeruginosa. Therefore, NET-mediated complement activation occurs via both AP- and non AP-based mechanisms, and AP-mediated complement activation during NETosis is dependent on CFP. These findings suggest that neutrophils could use their AP tool kit to readily activate complement on NETs and Gram-negative bacteria such as P. aeruginosa, whereas additional components present in the serum help to fix non-AP-mediated complement both on NETs and bacteria. This unique mechanism may play important roles in host defense, and help to explain specific roles of complement activation in NET-related diseases.

This work presents the investigation on a MEMS based optomechanical transducer for displacements or vibration regarding its cross-sensitivities to multidirectional input excitations. The principle of the optomechanical transducer is based on the modulation of the light flux passing through one static and one movable micromechanical aperture. This kind of transducer is of increasing interest for MEMS sensors since it has inherent benefits and can compete with state-ofthe- art readout concepts regarding its resolution. We have experimentally proven that the sensitivities of the device is 3.3 × 107 V/m in x-direction, 8.23 × 106 V/m in y-direction, while it is negligible in z-direction.

This paper reports a MEMS gradiometer consisting of two independent, laterally oscillating masses on a single chip with integrated optical readout featuring a responsitivity of 35V/T at resonant operation. The symmetrical design of the two masses offers high accuracy and low cost by using conventional MEMS batch fabrication technology. The sensing principle is based on lateral displacement of the masses actuated by Lorentz forces which modulates a light flux passing through a stationary mask and the moving mask integrated in the masses. Phase and intensity detected by photodiodes reveal information about the uniformity of an external applied magnetic field, hence, enables the measurement of gradient-, homogeneous- and offset gradient magnetic fields.

The functional principle of an optical gradient magnetic field sensor consisting of two independent laterally oscillating masses on a single chip is reported. These oscillations are caused by the Lorentz forces resulting from an alternating current through the masses interacting with a static magnetic field. Light is modulated by relative in-plane movement of the masses and a fixed frame and subsequently detected by two photodiodes. Evaluation of magnitude and phase of the output signal reveals information about the uniformity of the magnetic field. The sensor is capable of detecting uniaxially strength and direction of magnetic gradient fields, offset gradient fields and homogeneous fields.

This paper reports a novel 3D-printed MEMS resonant magnetometer with optical readout which features a mechanical conversion of a vertical oscillation into a horizontal one. This demonstrates the advantages of 3D-printing technology in terms of rapid prototyping, low costs and fast product development cycles. In addition, 3D-printing enables ‘true’ three-dimensional MEMS structures in contrast to the traditional MEMS technology which allows only two dimensional structures. The measurement approach comprises a hybrid implementation of an optical modulator, an LED and a photodetector.

This paper reports on a novel, miniaturized magnetomechanical transducer/sensor made of borosilicate glass with wide dynamic range. The prototype is manufactured with laser micromachining and ablation techniques. Compared to state of the art, borosilicate glass substrate offers the highest thermal shock resistance and is best suited for MEMS magnetometers, for aerospace and space applications or magnetic monitoring systems for diagnostics and plasma stability control of nuclear fusion experiments, where thermal shock resistance is a critical requirement.

This paper reports a novel 3D printed MEMS magnetometer with optical readout, which demonstrates the advantages of 3D printing technology in terms of rapid prototyping. Low-cost and fast product development cycles favour 3D printing as an effective tool. Sensitivity measurement with such devices indicate high accuracy and good structural performance, considering material and technological uncertainties. This paper is focusing on the novelty of the rapid, 3D-printing prototyping approach and verification of the working principle for printed MEMS magnetometers.

We report on a new optical sensing principle for measuring the electric field strength based on MEMS technology. This method allows for distortion-free and point-like measurements with high stability regarding temperature. The main focus of this paper rests on an enhanced measurement set-up and the thereby obtained measurement results. These results reveal an improved resolution limit and point to the limitations of the current characterization approach. A resolution limit of 222 V/m was achieved while a further improvement of roughly one order of magnitude is feasible.

Die künstlerische Forschung bietet neue Möglichkeiten und Herausforderungen für akademische Institute im Bereich Jazz und Popularmusik. In diesem Werkstattbericht über das kürzlich abgeschlossene künstlerische Forschungsprojekt Jazz & the City: Identität einer Jazz(haupt)stadt, das vom österreichischen Wissenschaftsfonds FWF im Rahmen des PEEK-Programms gefördert und in Kooperation der Institute für Jazz und Jazzforschung an der Kunstuniversität Graz durchgeführt wurde, wird versucht, eine Perspektive zur Entwicklung der bereits existenten, aber oftmals verdeckt stattfindenden künstlerischen Forschung vor dem Hintergrund der Geschichte dieser beiden Institute herauszuarbeiten. 30.03.2015 | Michael Kahr (Graz)

Cyclopentyl substituted silanetriol can be prepared and isolated. Its condensation yields the corresponding disiloxanetetrol as a primary condensation product. Further condensation leads to the hexameric polyhedral silsesquioxane cage T6. The latter has been mentioned in the literature before however, lacking structural data. All compounds have been characterized with multinuclear NMR spectroscopy and, in addition, the molecular structures have been determined in the case of the disiloxanetetrol and the hexasilsesquioxane via single crystal X-ray diffraction.

Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.

This article examines an educational design experiment which aimed to support young people’s involvement and reflection in the exhibition at a Danish science centre. The experiment consisted in the examination of the design and implementation of a mobile phone facilitated narrative, which was planned as a so-called scaffolding remedy in the hands-on based exhibition. The digital narrative, called EGO-TRAP, was developed using Design-Based Research as the overall methodological framework. The study of students’ interactions in the exhibition suggests, among other things, that because of its quality as a digital narrative, EGO-TRAP scaffolds pleasurable engagement and counteracts the tendency of "random button pressing" that often occurs in classical science centre exhibitions. In this connection, the mobile phone plays an essential role due to the fact that it, as the favoured media by the young students, offers an experience which they describe as both personal and flexible.