Elevated carbohydrate antigen 19-9 following Helicobacter suis gastritis and normalisation after eradication: first case report and review of the literature.

Carbohydrate antigen 19-9 (CA 19-9) is a biological marker used to diagnose and monitor the progression of various cancers. Elevated CA 19-9 has also been sporadically observed in Helicobacter pylori infected patients. Similar to H. pylori, animalhosted non-H. pylori Helicobacter (NHPH) species can induce gastroduodenal lesions in humans. We report the first case of CA 19-9 elevation related to H. suis gastritis and its normalisation after eradication. A CA 19-9 screening prescribed as part of a regular check up by the general practitioner was found elevated in a 68-year-old man presenting chronic dyspeptic symptoms. Medical investigations were negative for presence of neoplasia or biliary obstruction. Upper gastrointestinal endoscopy confirmed the presence of chronic gastritis and H. suis was identified in gastric biopsies. The standard treatment for H. pylori successfully eradicated H. suis with normalisation of CA 19-9 levels. In addition to H. pylori, infection with NHPH species should be considered as an additional cause of elevated CA19-9.

Self-referencing circular dichroism ion yield measurements for improved statistics using femtosecond laser pulses.

The combination of circular dichroism with laser mass spectrometry via the measurement of ion yields is a powerful tool in chiral recognition, but the measured anisotropies are generally weak. The method presented in this contribution reduces the measurement error significantly. A common path optical setup generates a pair of counter-rotating laser foci in the interaction region of a time-of-flight spectrometer. As the space focus condition is fulfilled for both foci individually, this becomes a twin-peak ion source with well separated and sufficiently resolved mass peaks. The individual control of polarization allows for in situ correction of experimental fluctuations measuring circular dichroism. Our robust optical setup produces reliable and reproducible results and is applicable for dispersion sensitive femtosecond laser pulses. In this contribution, we use 3-methyl-cyclopentanone as a prototype molecule to illustrate the evaluation procedure and the measurement principle.

Antimicrobial susceptibility pattern of Helicobacter suis isolates from pigs and macaques.

Helicobacter suis is a fastidious, Gram negative bacterium that colonizes the stomach of pigs and non-human primates. It has also been associated with gastric disease in humans. A combined agar and broth dilution method was used to analyze the activity of 15 antimicrobial agents against 20 and 15 H. suis isolates obtained from pigs and macaques, respectively. After 48 h microaerobic incubation, minimal inhibitory concentrations (MICs) were determined by software-assisted calculation of bacterial growth as determined by quantitative real-time PCR. A monomodal distribution of MICs was seen for ß-lactam antibiotics, macrolides, gentamicin, neomycin, doxycycline, metronidazole, and rifampicin. Presence of a bimodal distribution of MICs indicated that 2 porcine isolates did not belong to the wild type population (WTP) for fluoroquinolones. This was also the case for 1 porcine isolate for tetracycline, 1 porcine and 2 primate isolates for lincomycin, and 1 primate isolate for spectinomycin. Single nucleotide polymorphisms (SNPs) were present in the gyrA gene of the isolates not belonging to the WTP for fluoroquinolones and in ribosomal protein encoding genes of the isolates not belonging to the WTP for tetracycline and spectinomycin. MICs of ampicillin, tetracycline and doxycycline were higher for porcine H. suis isolates compared to primate isolates and in these porcine isolates SNPs were detected in genes encoding penicillin binding and ribosomal proteins. This study indicates that acquired resistance occasionally occurs in H. suis isolates and that zoonotically important porcine isolates may be intrinsically less susceptible to ß-lactam antibiotics and tetracyclines than primate isolates.

Warming and Inhibition of Salinization at the Ocean's Surface by Cyanobacteria.

This paper describes high-resolution in situ observations of temperature and, for the first time, of salinity in the uppermost skin layer of the ocean, including the influence of large surface blooms of cyanobacteria on those skin properties. In the presence of the blooms, large anomalies of skin temperature and salinity of 0.95°C and -0.49 practical salinity unit were found, but a substantially cooler (-0.22°C) and saltier skin layer (0.19 practical salinity unit) was found in the absence of surface blooms. The results suggest that biologically controlled warming and inhibition of salinization of the ocean's surface occur. Less saline skin layers form during precipitation, but our observations also show that surface blooms of Trichodesmium sp. inhibit evaporation decreasing the salinity at the ocean's surface. This study has important implications in the assessment of precipitation over the ocean using remotely sensed salinity, but also for a better understanding of heat exchange and the hydrologic cycle on a regional scale.

The role of infectious agents in the development of porcine gastric ulceration.

Ulceration of the non-glandular part of the stomach is a common disease entity of pigs worldwide, with prevalences of up to 93%. It may result in decreased daily weight gain, decreased feed intake and sudden death, thus leading to significant economic losses, as well as animal welfare issues. The aetiology is multifactorial. Diet particle size, management and infectious agents have been hypothesised to be involved. The exact mechanism behind porcine gastric ulceration is, however, not completely clear. The aim of this article is to provide an overview of the role of infectious agents in the development of porcine gastric ulceration. Results of recent studies indicate that Helicobacter suis infection plays an important role in gastric ulceration, probably by affecting gastric acid secretion through alteration of the number and/or function of parietal, D and G cells. In a gastric environment altered by H. suis, higher numbers of Fusobacterium gastrosuis are present and this novel pathogen has a potential role in the development of porcine gastric ulceration. Inoculation of pigs with Lactobacillus sp., Bacillus sp. or Helicobacter pylori-like bacteria in combination with a carbohydrate-rich diet may induce gastric lesions. It has been hypothesised that production of short chain fatty acids by some of these bacteria might be involved in the pathogenesis of porcine gastric ulceration, but the lack of taxonomic characterisation hampers the interpretation of these studies. Severe infectious diseases have also been associated with gastric lesions, probably due to interruption in feed intake and/or histamine release. Other agents, including fungi and parasites such as Hyostrongylus rubidus and Ascaris suum, have occasionally been associated with gastric lesions in pigs.

Presence of Helicobacter and Campylobacter species in faecal samples from zoo mammals.

Helicobacter and Campylobacter species (spp.) colonize the gastrointestinal tract of various domesticated animals. Apart from their pathogenic significance in animals, several species are of zoonotic importance as well. For most non-domesticated animal spp., however, little is known on the presence and importance of these agents. Therefore, we investigated the presence of Helicobacter and Campylobacter spp. in marine and terrestrial zoo mammals. Faecal samples of various marine and terrestrial zoo mammals were collected from 6 different zoos in Belgium. These samples were tested for the presence of Helicobacter and Campylobacter spp. by isolation and direct demonstration of DNA using genus-specific PCRs, followed by sequencing of the obtained amplicons. Helicobacter spp. were detected in 12 and Campylobacter spp. in 5 of the 22 faecal samples from marine mammals. In 4 of 5 dolphins, H. cetorum was demonstrated, a well-known pathogen associated with gastritis and gastric ulceration in marine mammals. C. insulaenigrae was isolated from 4 of 6 sea lions and from 1 of 11 seals. To our knowledge, this is the first description of the presence of C. insulaenigrae on the European mainland. Helicobacter spp. were detected in 5 and Campylobacter spp. (mainly C. jejuni subsp. jejuni and C. coli) in 9 of the 26 faecal samples from terrestrial mammals. Potential novel enterohepatic Helicobacter spp. were detected in both marine and terrestrial zoo mammals. For the first time, the presence of several known and unknown Campylobacter and Helicobacter spp. was demonstrated in the gastrointestinal tract of various marine and terrestrial zoo mammals. Further investigation is needed on the pathogenic and zoonotic importance of these species.

Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages.

Gastric mRNA expression of markers for acid secretion and inflammation and presence of gastric ulceration was studied in naturally Helicobacter suis-infected and non-infected 2-3 months old, 6-8 months old and adult pigs. In H. suis-infected 2-3 months old pigs, IL-8 and IL-1ß transcript levels were upregulated in the pyloric gland zone, indicating an innate immune response. A similar response was demonstrated in the fundic gland zone of adult pigs, potentially due to a shift of H. suis colonization from the pyloric to the fundic gland zone. A Treg response in combination with decreased expressions of IL-8, IL-17A and IFN-γ was indicated to be present in the H. suis-infected 6-8 months old pigs, which may have contributed to persistence of H. suis. In H. suis-infected adult pigs, a Treg response accompanied by a Th17 response was indicated, which may have played a role in the decreased number of H. suis bacteria in the stomach of this age group. The decreased G-cell mass and upregulated expression of somatostatin indicated decreased acid secretion in H. suis-infected 6-8 months old pigs. In H. suis-infected adult pigs, upregulation of most markers for gastric acid secretion and increased G-cell mass was detected. Presence of severe hyperkeratosis and erosions in the non-glandular part of the stomach were mainly seen in the H. suis-positive groups. These results show that H. suis infection affects the expression of markers for acid secretion and inflammation and indicate that these effects differ depending on the infection phase.

Detection, isolation and characterization of Fusobacterium gastrosuis sp. nov. colonizing the stomach of pigs.

Nine strains of a novel Fusobacterium sp. were isolated from the stomach of 6-8 months old and adult pigs. The isolates were obligately anaerobic, although they endured 2h exposure to air. Phylogenetic analysis based on 16S rRNA and gyrase B genes demonstrated that the isolates showed high sequence similarity with Fusobacterium mortiferum, Fusobacterium ulcerans, Fusobacterium varium, Fusobacterium russii and Fusobacterium necrogenes, but formed a distinct lineage in the genus Fusobacterium. Comparative analysis of the genome of the type strain of this novel Fusobacterium sp. confirmed that it is different from other recognized Fusobacterium spp. DNA-DNA hybridization, fingerprinting and genomic %GC determination further supported the conclusion that the isolates belong to a new, distinct species. The isolates were also distinguishable from these and other Fusobacterium spp. by phenotypical characterization. The strains produced indole and exhibited proline arylamidase and glutamic acid decarboxylase activity. They did not hydrolyse esculin, did not exhibit pyroglutamic acid arylamidase, valine arylamidase, α-galactosidase, ß-galactosidase, ß-galactosidase-6-phosphate or α-glucosidase activity nor produced acid from cellobiose, glucose, lactose, mannitol, mannose, maltose, raffinose, saccharose, salicin or trehalose. The major fatty acids were C16:0 and C18:1ω9c. The name Fusobacterium gastrosuis sp. nov. is proposed for the novel isolates with the type strain CDW1(T) (=DSM 101753(T)=LMG 29236(T)). We also demonstrated that Clostridium rectum and mortiferum Fusobacterium represent the same species, with nomenclatural priority for the latter.

Self-management education for rehabilitation inpatients suffering from inflammatory bowel disease: a cluster-randomized controlled trial.

Although inflammatory bowel disease (IBD) affects patients' psychological well-being, previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life. Therefore, we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management skills, delivered in an interactive manner, and evaluated it in a large, cluster-randomized trial. We assigned 540 rehabilitation inpatients suffering from IBD (mean age 43 years, 66% female) to either the new intervention or a control group comprising the same overall intensity and the same medical information, but only general psychosocial information. The primary outcome was patient-reported IBD-related concerns. Secondary outcomes included disease knowledge, coping, self-management skills, fear of progression, anxiety, depression and quality of life. Assessments took place at baseline, end of rehabilitation and after 3 and 12 months.The psychoeducational self-management program did not prove superior to the control group regarding primary and secondary outcomes. However, positive changes over time occurred in both groups regarding most outcomes. The superior effectiveness of the newly developed psychoeducational program could not be demonstrated. Since the intervention and control groups may have been too similar, this trial may have been too conservative to produce between-group effects.

Heart Rate Variability and Arrhythmic Burden in Pulmonary Hypertension.

A growing body of evidence indicates that sudden cardiac death constitutes a major cause of mortality in pulmonary hypertension (PH). As validated method to evaluate cardiac autonomic system dysfunction, alterations in heart rate variability (HRV) are predictive of arrhythmic events, particularly in left ventricular disease. Here, we sought to determine the clinical value of HRV assessment in PH. Sixty-four patients were allocated to different PH-subgroups in this prospectively conducted trial: 25 patients with pulmonary arterial hypertension (PAH), 11 patients with chronic thromboembolic PH (CTEPH), and 28 patients with COPD-induced PH. All patients underwent 24-h Holter electrocardiogram for HRV assessment by time- and frequency-domain analysis. Arrhythmic burden was evaluated by manual analysis and complementary automatic measurement of premature atrial and ventricular contractions. The results were compared to 31 healthy controls. The PAH patients offered a significantly higher mean heart rate (78.6 ± 10.4 bpm vs. 70.1 ± 10.3 bpm, p = 0.04), a higher burden of premature ventricular contractions (p < 0.01), and decreases in HRV (SDNN: p < 0.01; SDANN: p < 0.01; very low frequency: p < 0.01; low frequency/high frequency ratio: p < 0.01; total power: p = 0.02). In CTEPH patients, only the amount of premature ventricular contractions differed from controls (p < 0.01), whereas in COPD both premature atrial contraction count and frequency-domain-based HRV manifested significant differences. In conclusion, PAH appears to be primarily affected by HRV alterations and ventricular arrhythmic burden, indicating a high risk for malignant arrhythmic events.

Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and Risk Factors.

Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes as compared with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for females as compared with males (OR = 2.9;P= .05). Multivariable logistic regression revealed that independent risk factors for amyloid development were increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001), and nephritis (OR = 2.3;P= .01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis.

Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients.

Self-reported health-related quality of life in kindergarten children: psychometric properties of the Kiddy-KINDL.

OBJECTIVES: To assess the psychometric properties of the German self-reported version of the Kiddy-KINDL that measures Health Related Quality of Life (HRQoL) in 3 to 5 year old kindergarten children. STUDY DESIGN: The population of the study comprised baseline data of a longitudinal study whose main aim is to investigate self-reported health outcomes in young children (N = 317). METHODS: Missing values, the distribution of data, internal consistency (Cronbach's alpha and Guttman's lambda), and reliability (split half and two weeks test-retest) were analysed. To assess discriminant validity, mean differences were tested splitting the sample regarding socio-emotional competences (VBV 3-6), age and gender. Structural validity was investigated with Confirmatory Factor Analysis (CFA). RESULTS: Mean HRQoL was 69.79 (SD 16.84). Overall missing values were 8.1%, overall Cronbach's alpha was 0.75 and overall Guttman's lambda was 0.77; for the whole scale Spearman-Brown test for split half reliability resulted in 0.80 and ICC for test-retest in 0.83. Discriminant validity investigation differentiated groups with high and low socio-emotional competence and those children who were 4.5 years or older, compared to the younger ones. Differences between boys and girls were also found. CFA suggested two main dimensions: physical and socio-emotional. CONCLUSION: This preliminary validation of the Kiddy-KINDL in very young children shows satisfactory psychometric properties. However, results of the Cronbach's alpha, Guttman's lambda and the CFA depicted problems, mainly in the psychological dimension. Due to these we recommend to use the Kiddy-KINDL as an instrument with only two dimensions. Further studies in general population samples are needed.

[Current position on Vedolizumab for ulcerative colitis and Crohn's disease]. / Vedolizumab bei Colitis ulcerosa und Morbus Crohn: eine Standortbestimmung.

Vedolizumab, the first drug in the class of anti-integrin molecules, is newly approved for ulcerative colitis and Crohn's disease and can be prescribed in Germany since mid-2014. By a specific receptor binding a relatively gut-selective mode of action was achieved without the known side effects of the systemic immunosuppression of the anti-TNF-alpha antibodies. According to the present data the safety profile of Vedolizumab appears to be more favorable than that of the anti-TNF- alpha therapy. Vedolizumab is suitable for induction therapy in patients with ulcerative colitis and Crohn's disease, however the kinetic of response compared with the anti-TNF-alpha antibodies seems to be slower. For maintenance therapy the Vedolizumab data show a deep and sustained remission in patients initially responding to induction therapy with a lower loss of efficacy in the long-term treatment known from the anti-TNF-alpha therapy. On the basis of currently available data the efficacy of Vedolizumab in ulcerative colitis appears to be slightly better than in Crohn's disease.

Quantitative chemical exchange saturation transfer with hyperpolarized nuclei (qHyper-CEST): sensing xenon-host exchange dynamics and binding affinities by NMR.

The reversible binding of xenon to host molecules has found numerous applications in nuclear magnetic resonance studies. Quantitative characterization of the Xe exchange dynamics is important to understand and optimize the physico-chemical behavior of such Xe hosts, but is often challenging to achieve at low host concentrations. We have investigated a sensitive quantification technique based on chemical exchange saturation transfer with hyperpolarized nuclei, qHyper-CEST. Using simulated signals we demonstrated that qHyper-CEST yielded accurate and precise results and was robust in the presence of large amounts of noise (10%). This is of particular importance for samples with completely unknown exchange rates. Using these findings we experimentally determined the following exchange parameters for the Xe host cryptophane-A monoacid in dimethyl sulfoxide in one type of experiment: the ratio of bound and free Xe, the Xe exchange rate, the resonance frequencies of free and bound Xe, the Xe host occupancy, and the Xe binding constant. Taken together, qHyper-CEST facilitates sensitive quantification of the Xe exchange dynamics and binding to hydrophobic cavities and has the potential to analyze many different host systems or binding sites. This makes qHyper-CEST an indispensable tool for the efficient design of highly specific biosensors.

Microfluidic resonant cavities enable acoustophoresis on a disposable superstrate.

We demonstrate surface acoustic wave (SAW) induced microparticle manipulation in a microstructured disposable glass-polymer composite superstrate, positioned on a piezoelectric substrate with a single, slanted SAW transducer. An excited SAW was coupled from the piezoelectric substrate into the superstrate, which acted as a transversal resonator structure. We show that the energy transmitted into the superstrate allowed acoustophoretic particle manipulation, while the wide frequency response of the SAW transducer enabled tuneable pressure distributions confined by the microchannel layout. The configuration provides a significant tolerance in positioning - making assembly easy.

Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR.

Xenon is well known to undergo host-guest interactions with proteins and synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical pumping, allowing the investigation of highly dilute systems, it makes an ideal nuclear magnetic resonance probe for such host molecules. The utility of xenon as a probe can be further improved using Chemical Exchange Saturation Transfer using hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires a polarizer and xenon infusion system optimized for such measurements. We present the design of a hyperpolarizer and xenon infusion system specifically designed to meet the requirements of Hyper-CEST measurements. One key element of this design is preventing rubidium runaway, a chain reaction induced by laser heating that prevents efficient utilization of high photon densities. Using thermocouples positioned along the pumping cell we identify the sources of heating and conditions for rubidium runaway to occur. We then demonstrate the effectiveness of actively cooling the optical cell to prevent rubidium runaway in a compact setup. This results in a 2-3-fold higher polarization than without cooling, allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min of (129)Xe. The simplicity of this design also allows it to be retrofitted to many existing polarizers. Combined with a direction infusion system that reduces shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in unprecedented detail, allowing us to completely resolve peaks separated by just 1.62 ppm. Due to its high polarization and excellent stability, our design allows the comparison of underlying theories of host-guest systems with experiment at low concentrations, something extremely difficult with previous polarizers.

Development of auditory localization accuracy and auditory spatial discrimination in children and adolescents.

The present study investigated the development of two parameters of spatial acoustic perception in children and adolescents with normal hearing, aged 6-18 years. Auditory localization accuracy was quantified by means of a sound source identification task and auditory spatial discrimination acuity by measuring minimum audible angles (MAA). Both low- and high-frequency noise bursts were employed in the tests, thereby separately addressing auditory processing based on interaural time and intensity differences. Setup consisted of 47 loudspeakers mounted in the frontal azimuthal hemifield, ranging from 90° left to 90° right (-90°, +90°). Target signals were presented from 8 loudspeaker positions in the left and right hemifields (±4°, ±30°, ±60° and ±90°). Localization accuracy and spatial discrimination acuity showed different developmental courses. Localization accuracy remained stable from the age of 6 onwards. In contrast, MAA thresholds and interindividual variability of spatial discrimination decreased significantly with increasing age. Across all age groups, localization was most accurate and MAA thresholds were lower for frontal than for lateral sound sources, and for low-frequency compared to high-frequency noise bursts. The study also shows better performance in spatial hearing based on interaural time differences rather than on intensity differences throughout development. These findings confirm that specific aspects of central auditory processing show continuous development during childhood up to adolescence.

Electronic transport with dielectric confinement in degenerate InN nanowires.

In this Letter, we present the size effects on charge conduction in InN nanowires by comprehensive transport studies supported by theoretical analysis. A consistent model for highly degenerate narrow gap semiconductor nanowires is developed. In contrast to common knowledge of InN, there is no evidence of an enhanced surface conduction, however, high intrinsic doping exists. Furthermore, the room-temperature resistivity exhibits a strong increase when the lateral size becomes smaller than 80 nm and the temperature dependence changes from metallic to semiconductor-like. This effect is modeled by donor deactivation due to dielectric confinement, yielding a shift of the donor band to higher ionization energies as the size shrinks.

Extracting physically interpretable data from electron energy-loss spectra.

Principal component analysis is routinely applied to analyze data sets in electron energy-loss spectroscopy (EELS). We show how physically meaningful spectra can be obtained from the principal components using a knowledge of the scattering of the probe electron and the geometry of the experiment. This approach is illustrated by application to EELS data for the carbon K edge in graphite obtained using a conventional transmission electron microscope. The effect of scattering of the probe electron is accounted for, yielding spectra which are equivalent to experiments using linearly polarized X-rays. The approach is general and can also be applied to EELS in the context of scanning transmission electron microscopy.