Progress in Micro Joule-Thomson Cooling at Twente University

At the University of Twente, research on the development of a sorption-based micro cooler is in progress. Because of the absence of moving parts, such a cooler is virtually vibration free and highly durable, which potentially results in a long lifetime. A miniature cryogenic cooler with these properties would be appealing in a wide variety of applications including the cooling of vibration-sensitive detectors in space missions, low-noise amplifiers and semi- and superconducting circuitry. The objective of the present project is to scale down a Joule-Thomson (JT) cold stage to a total volume of a few hundredths of a cm3. This size reduction introduces many problems. The proposed cold stage volume results in a restriction cross-sectional area of about a thousandth of a mm2 which may cause clogging problems. Flow channels with a cross-sectional area of a few hundredths of a mm2 will produce high pressure drops influencing the JT cycle. Furthermore, the micro channels must be capable of withstanding high pressures and maintaining a large temperature gradient over a relatively short length. The project aim is to develop a reliable micro JT cold stage that is fabricated out of one material with a relatively simple and reproducible fabrication method. The length of the cold stage is calculated at about 20 mm with a width of 1.7 mm and height of about 0.3 mm. The mass flow is in the order of one mg per second to create a net cooling power of 10 mW at 96 K. The final objective of the project is to integrate the cold stage, vacuum chamber and device into one compact design. This paper discusses possible solutions to the problems mentioned and presents a concept design of such a miniature JT cold stage

Difference in signalling between various hormone therapies in endometrium, myometrium and upper part of the vagina

BACKGROUND: Combined hormone treatments in post-menopausal women have different clinical responses on uterus and vagina; therefore, we investigated differences in steroid signalling between various hormone therapies in these tissues. METHODS: A total of 30 post-menopausal women scheduled for hysterectomy were distributed into four subgroups: control-group (n = 9), Tibolone-group (n = 8); estradiol (E(2))-group (n = 7); E(2) + medroxyprogesterone acetate (MPA)-group (n = 6). Medication was administered orally every day for 21 days prior to removal of uterus and upper part of the vagina. Tissue RNA was isolated, and gene expression profiles were generated using GeneChip technology and analysed by cluster analysis and significance analysis of microarrays. Apoptosis and cell proliferation assays, as well as immunohistochemistry for hormone receptors were performed. RESULTS: 21-days of treatment with E(2), E(2) + MPA or tibolone imposes clear differential gene expression profiles on endometrium and myometrium. Treatment with E(2) only results in the most pronounced effect on gene expression (up to 1493 genes differentially expressed), proliferation and apoptosis. Tibolone, potentially metabolized to both estrogenic and progestagenic metabolites, shows some resemblance to E(2) signalling in the endometrium and, in contrast, shows significant resemblance to E(2) + MPA signalling in the myometrium. In the vagina the situation is entirely different; all three hormonal treatments result in regulation of a small number (4-73) of genes, in comparison to signalling in endometrium and myometrium. CONCLUSION: Endometrium and myometrium differentially respond to the hormone therapies and use complet

Building an international network for a primary care research program: reflections on challenges and solutions in the set-up and delivery of a prospective observational study of acute cough in 13 European countries

BACKGROUND: Implementing a primary care clinical research study in several countries can make it possible to recruit sufficient patients in a short period of time that allows important clinical questions to be answered. Large multi-country studies in primary care are unusual and are typically associated with challenges requiring innovative solutions. We conducted a multi-country study and through this paper, we share reflections on the challenges we faced and some of the solutions we developed with a special focus on the study set up, structure and development of Primary Care Networks (PCNs).METHOD: GRACE-01 was a multi-European country, investigator-driven prospective observational study implemented by 14 Primary Care Networks (PCNs) within 13 European Countries. General Practitioners (GPs) recruited consecutive patients with an acute cough. GPs completed a case report form (CRF) and the patient completed a daily symptom diary. After study completion, the coordinating team discussed the phases of the study and identified challenges and solutions that they considered might be interesting and helpful to researchers setting up a comparable study.RESULTS: The main challenges fell within three domains as follows:i) selecting, setting up and maintaining PCNs;ii) designing local context-appropriate data collection tools and efficient data management systems; andiii) gaining commitment and trust from all involved and maintaining enthusiasm.The main solutions for each domain were:i) appointing key individuals (National Network Facilitator and Coordinator) with clearly defined tasks, involving PCNs early in the development of study materials and procedures.ii) rigorous back translations of all study materials and the use of information systems to closely monitor each PCNs progress;iii) providing strong central leadership with high level commitment to the value of the study, frequent multi-method communication, establishing a coherent ethos, celebrating achievements, incorporating social events and prizes within meetings, and providing a framework for exploitation of local data.CONCLUSIONS: Many challenges associated with multi-country primary care research can be overcome by engendering strong, effective communication, commitment and involvement of all local researchers. The practical solutions identified and the lessons learned in implementing the GRACE-01 study may assist in establishing other international primary care clinical research platforms

Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC4 E): the ALIC4 E protocol

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations

Integrative Analysis of the Mitochondrial Proteome in Yeast

In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Design av en fasstyrd gruppantenn med en bandpass frekvensselektiv yta hybrid radom : Analys och karaktärisering av en frevensselektiv yta och en fasstyrd gruppantenn

A circular polarised phased array antenna and a frequency selective hybrid radome are designed and evaluated. The antenna system is well suited as a part of a communication link between platforms with a 600 MHz bandwidth and a centre frequency of 5 GHz. A prototype consisting of 8 x 8 patch elements has been designed, manufactured and characterised. The final configuration will be a compact, relatively inexpensive system with single-fed antenna elements. An array antenna with circular polarisation is suitable when the receiver must maintain a strong signal regardless of the relative antenna orientation. The radome protects the antenna and can also reduce both the radar cross section and interference from out-of-band signals. The main focus is to make sure that the phased array antenna and the radome work as one unit and maximise the field of view in which the polarisation is circular. The method to maximise the field of view is to reduce the coupling between antenna elements by using shorting via fences surrounding each element. Following this method results in a total array gain of 18 dBi, 25° half-power beamwidth and a ±35° maximum scan angle with maintained circular polarisation. Prototype measurements agree well with the simulated results.En cirkulärpolariserad fasstyrd gruppantenn samt en frekvensselektiv hybrid-radom har designats och utvärderats. Antennsystemet lämpar sig väl som en kommunikationslänk mellan plattformar med en 600 MHz bandbredd och centerfrekvens 5 GHz. En prototyp besåtende av 8 × 8 patchelement har designats, tillverkats och karaktäriserats. Den slutgiltiga konfigurationen resulterade i ett kompakt och relativt billigt system med single-matade antennelement. En gruppantenn med cirkulär polarisation är lämplig när mottagaren måste bibehålla en stark signal oavsett antennens relativa orientering. Radomen skyddar antennen från väder och vind och kan även minska både radarmålsarean och störningar från utombandiga signaler. Huvudfokus är att se till att den fasstyrda gruppantennen och radomen fungerar som en enhet och maximerar scan-området i vilket polarisationen är cirkulär. Metoden för att maximera detta område är att minska kopplingen mellan antennelementen genom att använda ett kortslutande viastaket som omsluter varje element. Metoden resulterar i totalt 18 dBi array gain, 25° half-power beamwidth och en maximal utstyrningsvinkel på ±35° med bibehållen cirkulär polarisation. Prototypens mätresultat stämmer väl överens med simulationsresultaten

A Discrete Cylindrical Luneburg Lens With Liquid Layers

In this project, a cylindrical Luneburg lens isdesigned operating at optical frequencies. A Luneburg lens isa gradient index lens that transforms a point source into aplane wave or vice versa. The lens is rotational symmetric whichallows wide-angle beam scan. In this work, the gradient indexis discretized in layers. The refractive index of each layer isrealized with a transparent liquid. Ray tracing is used to designand evaluate the lens performance. We have simulated Luneburglenses with 4 - 10 layers. Increasing the number of layersimproves the performance. However, difficulties are present inthe manufacturing part of the lens considering that liquids withdesired refractive index cannot be mixed.I detta projekt designas en cylindrisk Luneburg-lins som fungerar vid optiska frekvenser. En Luneburg-lins är en gradientindexlins som omvandlar en punktkälla till en plan våg eller vice versa. Linsen är rotationssymmetrisk vilket möjliggör vidvinkelstrålescanning. I detta arbete diskretiseras gradienta indexet i lager, brytningsindex för varje lager realiseras med en transparent vätska. Raytracing används för att designa och utvärdera linsprestandan. Vi har simulerat Luneburg-linser med 4 - 10 lager. Genom att öka antalet lager förbättras prestandan. Svårigheter förekommer i linsens tillverkningsprocess med tanke på att vätskor med önskat brytningsindex inte kan blandas.Kandidatexjobb i elektroteknik 2020, KTH, Stockhol