A Versatile Magnetorquer Design for Microsatellite Constellation Missions

Attitude determination and control hardware for small satellites is constantly transforming to improve pointing accuracy and stability for target tracking missions. Magnetic attitude control is an effective and inexpensive approach when developing microsatellites for low earth orbit constellation missions. The Space Flight Laboratory (SFL) has implemented magnetic torquers (magnetorquers) and permanent magnets in previous missions for active and passive magnetic attitude control. A magnetorquer generates a magnetic dipole that torques the spacecraft when in the presence of Earth’s magnetic field. This paper outlines the design, analysis, and testing of an embedded coil magnetorquer for SFL’s SPARTAN and DEFIANT platforms. The SPARTAN magnetorquer was designed to be easily adaptable to other SFL platforms, including the DEFIANT platform which is shown to have only minor modifications. Simulations of sample missions for both platforms show how the magnetorquers are able to detumble the spacecraft after launch vehicle separation as well as mitigate reaction wheel saturation. All flight magnetorquers must go through environmental acceptance testing before they are ready for spacecraft integration. A set of three identical magnetorquers are orthogonally mounted in their respective platforms to enable magnetic dipole generation in all three body axes

Synthesis of Allylnickel Aryloxides and Arenethiolates: Study of Their Dynamic Isomerization and 1,3-Diene Polymerization Activity

A new family of allylnickel(I1) complexes, [Ni(η^3-+allyl)(µ-X)]_2 (X = ArO, ArS), have been synthesized by anion metathesis of the sodium or lithium salts of aryloxides or arenethiolates with [Ni(η^3-allyl)(µ-Br)]_2. The complexes are proposed to be dimeric and to consist of a mixture of cis and trans isomers. A dynamic process rapidly equilibrates the cis and trans isomers of the pentafluorophenoxide, 2,6-difluorophenoxide, and 3,5-bis(trifluoromethyl)phenoxide complexes on the ^1H NMR time scale. The 2,6-dimethylphenoxide, 2,6-diisopropylphenoxide, 2,4,6- tris(trifluoromethyl)phenoxide, and pentafluorothiophenoxide complexes are static at room temperature. A variable-temperature NMR study of the 3,5-bis(trifluoromethyl)phenoxide complex provided activation enthalpy and entropy values of 12.9 kcal/mol and -6.6 cal/ (K mol), respectively. Allyl rotation or cleavage of one of the µ-X bridges is proposed as the mechanism for the isomerization. The pentafluorophenoxide, 3,5-bis(trifluoromethyl)phenoxide, and 2,4,6-tris(trifluoromethy1)phenoxide complexes initiate the rapid polymerization of 1,3-cyclohexadiene and 1,3-butadiene to form high-molecular weight, 1,4-linked polymers

Ocean Futures for the World’s Largest Yellowfin Tuna Population Under the Combined Effects of Ocean Warming and Acidification

The impacts of climate change are expected to have profound effects on the fisheries of the Pacific Ocean, including its tuna fisheries, the largest globally. This study examined the combined effects of climate change on the yellowfin tuna population using the ecosystem model SEAPODYM. Yellowfin tuna fisheries in the Pacific contribute significantly to the economies and food security of Pacific Island Countries and Territories and Oceania. We use an ensemble of earth climate models to project yellowfin populations under a high greenhouse gas emissions (IPCC RCP8.5) scenario, which includes, the combined effects of a warming ocean, increasing acidification and changing ocean chemistry. Our results suggest that the acidification impact will be smaller in comparison to the ocean warming impact, even in the most extreme ensemble member scenario explored, but will have additional influences on yellowfin tuna population dynamics. An eastward shift in the distribution of yellowfin tuna was observed in the projections in the model ensemble in the absence of explicitly accounting for changes in acidification. The extent of this shift did not substantially differ when the three-acidification induced larval mortality scenarios were included in the ensemble; however, acidification was projected to weaken the magnitude of the increase in abundance in the eastern Pacific. Together with intensive fishing, these potential changes are likely to challenge the global fishing industry as well as the economies and food systems of many small Pacific Island Countries and Territories. The modelling framework applied in this study provides a tool for evaluating such effects and informing policy development

Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function.

Aims: Cardiac resynchronization therapy (CRT) may exert its beneficial haemodynamic effect by improving ventricular synchrony and improving atrioventricular (AV) timing. The aim of this study was to establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronization. Methods and Results: We performed simulations using the CircAdapt haemodynamic model and performed haemodynamic measurements while adjusting AV delay, at low and high heart rates, in 87 patients with CRT devices. We assessed QRS duration, presence of fusion, and haemodynamic response. The simulations suggest that intrinsic PR interval and the magnitude of reduction in ventricular activation determine the relative importance of the mechanisms of benefit. For example, if PR interval is 201 ms and LV activation time is reduced by 25 ms (typical for current CRT methods), then AV delay optimization is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25 ms produced an additional 2.6 mmHg increase in blood pressure (30% of effect size observed with current CRT). In the clinical population, ventricular fusion significantly shortened QRS duration (Δ-27 ± 23 ms, P < 0.001) and improved systolic blood pressure (mean 2.5 mmHg increase). Ventricular fusion was present in 69% of patients, yet in 40% of patients with fusion, shortening AV delay (to a delay where fusion was not present) produced the optimal haemodynamic response. Conclusions: Improving LV preloading by shortening AV delay is an important mechanism through which cardiac function is improved with CRT. There is substantial scope for further improvement if methods for delivering more efficient ventricular resynchronization can be developed. Clinical Trial Registration: Our clinical data were obtained from a subpopulation of the British Randomised Controlled Trial of AV and VV Optimisation (BRAVO), which is a registered clinical trial with unique identifier: NCT01258829, https://clinicaltrials.gov

Comparison of ALitretinoin with PUVA as the first-line treatment in patients with severe chronic HAnd eczema (ALPHA):study protocol for a randomised controlled trial

Introduction Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. The 1-year prevalence of HE is estimated to be up to 10% and it is estimated that 5%–7% of those develop severe chronic HE. However, current clinical evidence is not compelling enough to guide clinical practice. In a survey among 194 UK dermatologists the most frequent first choice approaches were psoralen combined with ultraviolet A (UVA) treatment (PUVA), oral steroids and alitretinoin (AL). When asked which strategy was most efficient for long-term outcome 20% of clinicians indicated they did not know; 43% of clinicians reported AL and 30% reported PUVA. Methods and analysis ALPHA is a multicentre, open, prospective, two-arm parallel group, randomised controlled trial comparing PUVA and AL with a planned sample size re-estimation. Between 500 and 780 participants will be randomised on a 1:1 basis. The physician’s global assessment (PGA) will direct treatment after randomisation, non-responders will be treated according to usual clinical practice; providing valuable pilot data on second line therapeutic approaches to inform future trials. Assessments will be conducted up to 52 weeks post randomisation. The primary outcome measure is the Hand Eczema Severity Index at 12 weeks. Secondary outcome measures include modified Total Lesion Symptom Score, PGA, time to relapse, patient reported outcome measures and DNA extraction and assessment of genetic variants. A substudy on molecular inflammatory mediators will provide information on subgroup specific treatment responses. Photographs will be taken and HE severity assessed by a central review panel

Man of Letters, Literary Lady, Journalist or Reporter?

The enormous changes wrought in the British newspaper industry during the late nineteenth and early twentieth centuries brought about a revolution in newspaper reading habits, financing and influence, all aspects of which have been well-documented by historians of the press. But what of the contributor, particularly the freelance whose millions of words formed, mostly anonymously, the content of the new mass market press? How did writers negotiate changes in the literary marketplace during this time as editors demanded more ‘news’ and less in the way of whimsical paragraphing, and sketches, the traditional newspaper output of the professional man, or woman, of letters? Through the study of memoirs, correspondence and the fictional output of contributors to the press during this time, it is possible to discern the often fraught relations between writers and their most lucrative market

OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice

BACKGROUND: Tuberculosis (TB) is still a leading cause of death worldwide. Almost a third of the world's population is infected with TB bacilli, and each year approximately 8 million people develop active TB and 2 million die as a result. Today's TB treatment, which dates back to the 1970s, is long and burdensome, requiring at least 6 mo of multidrug chemotherapy. The situation is further compounded by the emergence of multidrug-resistant TB (MDR-TB) and by the infection's lethal synergy with HIV/AIDS. Global health and philanthropic organizations are now pleading for new drug interventions that can address these unmet needs in TB treatment. METHODS AND FINDINGS: Here we report OPC-67683, a nitro-dihydro-imidazooxazole derivative that was screened to help combat the unmet needs in TB treatment. The compound is a mycolic acid biosynthesis inhibitor found to be free of mutagenicity and to possess highly potent activity against TB, including MDR-TB, as shown by its exceptionally low minimum inhibitory concentration (MIC) range of 0.006–0.024 μg/ml in vitro and highly effective therapeutic activity at low doses in vivo. Additionally, the results of the post-antibiotic effect of OPC-67683 on intracellular Mycobacterium tuberculosis showed the agent to be highly and dose-dependently active also against intracellular M. tuberculosis H37Rv after a 4-h pulsed exposure, and this activity at a concentration of 0.1 μg/ml was similar to that of the first-line drug rifampicin (RFP) at a concentration of 3 μg/ml. The combination of OPC-67683 with RFP and pyrazinamide (PZA) exhibited a remarkably quicker eradication (by at least 2 mo) of viable TB bacilli in the lung in comparison with the standard regimen consisting of RFP, isoniazid (INH), ethambutol (EB), and PZA. Furthermore, OPC-67683 was not affected by nor did it affect the activity of liver microsome enzymes, suggesting the possibility for OPC-67683 to be used in combination with drugs, including anti-retrovirals, that induce or are metabolized by cytochrome P450 enzymes. CONCLUSIONS: We concluded that based on these properties OPC-67683 has the potential to be used as a TB drug to help combat the unmet needs in TB treatment

Effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for patients with moderate-to-severe psoriasis: a cohort study from BADBIR

Background Real-world data evaluating effectiveness and persistence of systemic therapies for patients with psoriasis are limited. Objectives To determine the effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters (FAEs) and methotrexate in patients with moderate-to-severe psoriasis. Methods Data from The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective, multi-centre pharmacovigilance register of patients with moderate-to-severe psoriasis receiving biologic and/or conventional systemic therapies, were analysed. Eligible patients were ≥16 years of age receiving a first course of acitretin, ciclosporin, FAEs or methotrexate between 2007 and 2021 with ≥6 months’ follow-up. Effectiveness was defined as achieving absolute Psoriasis Area and Severity Index (aPASI) ≤ 2 reported ≥4 weeks after treatment start date until stop date. To identify baseline clinical variables associated with treatment effectiveness, we used multivariable logistic regression models estimating the adjusted odds ratio (aOR) of achieving aPASI ≤2. To describe drug persistence associated with ineffectiveness, occurrence of adverse events or other reasons of discontinuation, survival estimates with 95% confidence interval (CI) were obtained using a flexible parametric model. Results were obtained using multiple imputed data. Results In total, 5430 patients were included in the analysis: 1023 (19%) on acitretin, 1401 (26%) ciclosporin, 347 (6%) FAEs and 2659 (49%) methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower with acitretin 118 (21%) compared with those on ciclosporin 233 (34%), FAEs 43 (30%) and methotrexate 372 (32%). Factors associated with ineffectiveness included prior experience to previous non-biologic systemic therapies (acitretin) [(aOR, (95% CI) 0.64 (0.42, 0.96)], male sex (methotrexate) 0.58 (0.46, 0.74), co-morbidities 0.70 (0.51, 0.97) and alcohol consumption (≤14 units per week) (ciclosporin) 0.70 (0.50, 0.98). Persistence associated with all reasons of discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [(Survival estimate (95% CI), 46.1 (44.0, 48.3), 31.9 (29.4, 34.7), 30.0 (27.5, 32.4) and 35.0 (29.9, 40.9)], respectively. Conclusions The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous non-biologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness