The Exponentially Weighted Moving Average Procedure for Detecting Changes in Intensive Longitudinal Data in Psychological Research in Real-Time:A Tutorial Showcasing Potential Applications

Affect, behavior, and severity of psychopathological symptoms do not remain static throughout the life of an individual, but rather they change over time. Since the rise of the smartphone, longitudinal data can be obtained at higher frequencies than ever before, providing new opportunities for investigating these person-specific changes in real-time. Since 2019, researchers have started using the exponentially weighted moving average (EWMA) procedure, as a statistically sound method to reach this goal. Real-time, person-specific change detection could allow (a) researchers to adapt assessment intensity and strategy when a change occurs to obtain the most useful data at the most useful time and (b) clinicians to provide care to patients during periods in which this is most needed. The current paper provides a tutorial on how to use the EWMA procedure in psychology, as well as demonstrates its added value in a range of potential applications.</p

Zingen en zorg voor de ziel, Een onderzoek naar hoe zingen als weg tot zinervaring kan bijdragen aan existentiële begeleiding

Een onderzoek naar hoe zingen als weg tot zinervaring kan bijdragen aan existentiële begeleiding In mijn scriptie heb ik onderzocht welke bijdrage zingen kan leveren in existentiële begeleiding. Iedereen zingt wel eens, in een koor, op een verjaardag of in een voetbalstadion. Aan zingen kunnen we veel plezier beleven, maar we kunnen ons er ook vreselijk ongemakkelijk bij voelen. Muziek kan ons diep raken en onze stem is onze eigen unieke klank, waarin al snel hoorbaar wordt hoe wij ons voelen. Zingen raakt aan wie wij als uniek mens in wezen zijn en dat voelt kwetsbaar. Daarmee is zingen echter ook een manier om te komen bij wat er in ons leeft, dit uit te drukken en te delen met anderen. In existentiële begeleiding begeven we ons op het terrein van zingeving. Hierin wordt veelal gewerkt met gesprekken. Zingeving behelst, naast een cognitief, reflectief en evaluatief proces, ook een emotioneel en affectief ervaren van zin of betekenis, of juist het ontbreken daarvan. In het beleven en uitdrukken van onze ervaringen of het daarin steun bieden aan anderen, kunnen woorden soms tekort schieten. Zingen kan, als weg naar binnen, als weg van zelfexpressie, en als weg tot verbondenheid, een weg zijn tot zinervaring en daarmee tot zingeving. Zingen kan ons een bedding geven voor het ervaren, onderzoeken, uiten en delen van onze gevoelens en diepe innerlijke ervaringen, ook wanneer woorden tekort schieten. Zingen kan ons houvast bieden in het spanningsveld tussen betekenisgeving en vertwijfeling en ons proces van zingeving bevorderen en ondersteunen. Zingen kan daarmee een krachtige aanvulling zijn op het instrumentarium van de existentieel begeleider. Bovendien kan zingen gezien worden als een weg om aan het humanisme, waarin de mens centraal staat, het streven naar een goed, zinvol, mooi persoonlijk leven en een humane samenleving, gestalte te geven en biedt het een humanistische vorm voor een non-verbaal, symbolisch, ritueel raadswerk

Silicon-on-insulator shortwave infrared wavelength meter with integrated photodiodes for on-chip laser monitoring

This paper demonstrates a very compact wavelength meter for on-chip laser monitoring in the shortwave infrared wavelength range based on an optimized arrayed waveguide grating (AWG) filter with an integrated photodiode array. The AWG response is designed to obtain large nearest neighbor crosstalk (i. e. large overlap) between output channels, which allows accurately measuring the wavelength of a laser under test using the centroid detection technique. The passive AWG is fabricated on a 220 nm silicon-on-insulator (SOI) platform and is combined with GaInAsSb-based photodiodes. The photodiodes are heterogeneously integrated on the output grating couplers of the AWG using DVS-BCB adhesive bonding. The complete device with AWG and detectors has a footprint of only 2 mm(2) while the measured accuracy and resolution of the detected wavelength is better than 20pm. (C)2014 Optical Society of Americ

6-Mercaptopurine, still valuable for the palliative treatment of acute myeloid leukaemia

Although 6-mercaptopurine (6-MP) is frequently used in the treatment of acute myeloid leukaemia (AML), its effect on disease progression has not been studied systematically. In a small retrospective analysis, we found that 6-MP could induce marked haematological improvement in a considerable number of AML patients who were not treated with intensive remission induction courses. Due to the inherent limitations of retrospective analyses, we then investigated prospectively in 51 consecutive patients over a 3-year period in a single centre, to what extent, oral 6-MP 250 mg twice a week could be beneficial to AML patients who were not-or no longer-eligible for intensive chemotherapy. Clinical response was scored according to changes in blood cell counts and dependency on blood transfusions. Thirteen patients (25%) were considered responders since they showed an increased platelet count from the first month after initiation of 6-MP onwards and they became independent of blood transfusions after 3 months. This effect lasted for 13 (range 7-30+) months. Median overall survival of this subgroup was 16.5 (6-33+) months. Ten patients (20%) had a shorter or incomplete response and a survival of 12 (6-30) months. Seven patients were lost to follow-up. Twenty-one (41%) failed to respond and survived for 4 (1.5-17) months. The response seemed not to be affected by previous chemotherapy, history of myelodysplasia, or karyotype abnormalities, but high leukocyte count initially was unfavourable. 6-MP thus can induce marked improvement of blood cell counts in a considerable proportion of AML patients who are not eligible for intensive chemotherapy, leading to good quality of life and a significant prolongation of survival.</p

Isolation of ‘Candidatus Nitrosocosmicus franklandus’, a novel ureolytic soil archaeal ammonia oxidiser with tolerance to high ammonia concentration

Acknowledgements The authors would like to thank Mr Kevin Mackenzie and Mrs Gillian Milne (University of Aberdeen) for technical support with scanning electron microscopy, and Dr Robin Walker for access to the Woodlands Field experimental plots at the SRUC,Craibstone Estate, Aberdeen. Funding This work was financially supported by Natural Environmental Research Council (standard grants NE/I027835/1 and NE/L006286/1 and fellowship NE/J019151/1), EC Marie Curie ITN NORA, Grant Agreement No. 316472, the AXA Research Fund and the Centre for Genome Enabled Biology and Medicine, University of Aberdeen.Peer reviewedPublisher PD

Obstructive pulmonary disease in patients with previous tuberculosis: Pathophysiology of a community-based cohort

Background. An association between chronic airflow limitation (CAL) and a history of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies, but the mechanisms responsible for this association are unclear. It is debated whether CAL in this context should be viewed as chronic obstructive pulmonary disease (COPD) or a separate phenotype. Objective. To compare lung physiology and high-resolution computed tomography (HRCT) findings in subjects with CAL and evidence of previous (healed) PTB with those in subjects with smoking-related COPD without evidence of previous PTB. Methods. Subjects with CAL identified during a Burden of Obstructive Lung Disease (BOLD) study performed in South Africa were studied. Investigations included questionnaires, lung physiology (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT scans to assess bronchial anatomy and the presence of emphysema (–200 HU). Findings in subjects with a past history and/or HRCT evidence of PTB were compared with those in subjects without these features. Results. One hundred and seven of 196 eligible subjects (54.6%) were enrolled, 104 performed physiology tests and 94 had an HRCT scan. Based on history and HRCT findings, subjects were categorised as no previous PTB (NPTB, n=31), probable previous PTB (n=33) or definite previous PTB (DPTB, n=39). Subjects with DPTB had a lower diffusing capacity (Δ=–17.7%; p=0.001) and inspiratory capacity (Δ=–21.5%; p=0.001) than NPTB subjects, and higher gas-trapping and fibrosis but not emphysema scores (Δ=+6.2% (p=0.021), +0.36% (p=0.017) and +3.5% (p=0.098), respectively). Conclusions. The mechanisms of CAL associated with previous PTB appear to differ from those in the more common smoking-related COPD and warrant further study..info:eu-repo/semantics/publishedVersio

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors:the phase 1 BNT211-01 trial

The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278 .</p