Methods for calibrating the gain and offset of the DSSC detector for the European XFEL

The DEPFET Sensor with Signal Compression (DSSC) will be a 2d 1Mpx imaging detector for the European X-­ray Free Electron Laser Facility (XFEL.EU). The DSSC is foreseen as an imaging detector for soft X-­radiation from 0.5 keV up to 6 keV. Driven by its scientific requirements, the design goals of the detector system are single photon detection, a high dynamic range and a high frame rate of up to 4.5 MHz. Signal compression, amplification and digitization will be performed in the focal plane. Utilizing an in-­pixel active filtering stage and an 8/9-­bit ADC, the detector will provide parallel readout of all pixels. Here the results of studies on the stability and performance of a parameterized model for determining gain and offset in DSSC prototype calibration line spectra will be presented

'Gut health': a new objective in medicine?

'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Methods for Calibrating the Gain and Offset of the DSSC Detector for the European XFEL

The DEPFET Sensor with Signal Compression (DSSC) will be a 2d 1Mpx imaging detector for the European X-ray Free Electron Laser facility (XFEL.EU), that is currently under construction in Hamburg. The DSSC is foreseen as a photon counting detector for soft X-ray radiation from 0.5 keV up to 6 keV. Driven by its scientific requirements, the design goals of the detector system are foremost low noise, a high dynamic range and a high frame rate of up to 4.5 MHz. Signal compression, amplification and digitization will be performed in the focal plane. Utilizing an in-pixel active filtering stage and an 8/9-bit ADC, the detector will provide parallel readout of all pixels. A critical step of calibrating the detector is the determination of the system gain and offset based on peak energies of X-ray calibration line sources such as $-{55}Fe$. This is demanding due to the intrinsically low spectral resolution of the DSSC. The results of studies on the stability and performance of automated procedures for peak fitting in single pixel spectra with a low energy resolution were presented on a poster

Methods for Calibrating the Gain and Offset of the DSSC Detector for the European XFEL

The DEPFET Sensor with Signal Compression (DSSC) will be a 2d 1Mpx imaging detector for the European X-­ray Free Electron Laser Facility (XFEL.EU). The DSSC is foreseen as an imaging detector for soft X-­radiation from 0.5 keV up to 6 keV. Driven by its scientific requirements, the design goals of the detector system are single photon detection, a high dynamic range and a high frame rate of up to 4.5 MHz. Signal compression, amplification and digitization will be performed in the focal plane. Utilizing an in-­pixel active filtering stage and an 8/9-­bit ADC, the detector will provide parallel readout of all pixels. Here the results of studies on the stability and performance of a parameterized model for determining gain and offset in DSSC prototype calibration line spectra will be presented

Study of Systematic and Statistical Uncertainty in Offset, Noise, and Gain Determination of the DSSC Detector for the European XFEL

The DSSC (DEPFET Sensor with Signal Compression) is a new instrument with non-linear response and parallel signal processing (filtering, linear amplification, and 8-bit digitization) for all pixels. The DSSC will serve as ultra-fast megapixel imaging detector at the European XFEL (X-ray Free Electron Laser) in Schenefeld, Germany, which began science operation in September this year. The DSSC detector needs to be calibrated for each of a set of twelve predefined operation modes before being employed in scientific experiments. A crucial step in the calibration of the response of each individual detector pixel is the calibration of offset and gain. We present a study of both systematic and statistical uncertainty in the determination of offset, noise, and gain. The best possible calibration of offset and gain requires that these two quantities can be determined with an uncertainty that is less than half the finite resolution of the respective read-out ASIC calibration settings. The study is based on simulated calibration data, which were then analyzed using our calibration tools. Systematic and statistical uncertainty in offset, noise, and gain determination was quantified by comparing analysis results with the actual values employed in the simulations. A review of all results identified the most suitable calibration approaches. Their ability for providing the best possible offset and gain calibration is discussed

Development of Large-Scale Functional Networks over the Lifespan

The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18–89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2–4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence

Changes in cortical slow wave activity in healthy aging

A number of studies have demonstrated enhanced slow wave activity associated with pathological brain function e.g. in stroke patients, schizophrenia, depression, Morbus Alzheimer, and post-traumatic stress disorder. However, the association between slow wave activity and healthy aging has remained largely unexplored. This study examined whether the frequency at which focal generators of delta waves appear in the healthy cerebral cortex changes with age and whether this measure relates to cognitive performance. We investigated 53 healthy individuals aged 18 to 89 years and assessed MEG during a resting condition. Generators of focal magnetic slow waves were localized. Results showed a significant influence of age: dipole density decreases with increasing age. The relationship between cognitive performance and delta dipole density was not significant. The results suggest that in healthy aging slow waves decrease with aging and emphasize the importance of age-matched control groups for further studies. Increased appearance of slow waves as a marker for pathological stages can only be detected in relation to a control group of the same age

Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100-250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer's dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI;n= 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (β= 0.38,p= 0.003;β= -0.27,p= 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (β= 0.57,p= 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia.publishe

Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100–250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer’s dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (β = 0.38, p = 0.003; β = −0.27, p = 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (β = 0.57, p = 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia