Electron beam fabrication and characterization of high- resolution magnetic force microscopy tips

The stray field, magnetic microstructure, and switching behavior of high‐resolution electron beam fabricated thin film tips for magnetic force microscopy (MFM) are investigated with different imaging modes in a transmission electron microscope (TEM). As the tiny smooth carbon needles covered with a thermally evaporated magnetic thin film are transparent to the electron energies used in these TEMs it is possible to observe both the external stray field emanating from the tips as well as their internal domain structure. The experiments confirm the basic features of electron beam fabricated thin film tips concluded from various MFM observations using these tips. Only a weak but highly concentrated stray field is observed emanating from the immediate apex region of the tip, consistent with their capability for high resolution. It also supports the negligible perturbation of the magnetization sample due to the tip stray field observed in MFM experiments. Investigation of the magnetization distributions within the tips, as well as preliminary magnetizing experiments, confirm a preferred single domain state of the high aspect ratio tips. To exclude artefacts of the observation techniques both nonmagnetic tips and those supporting different magnetization states are used for comparison

Spontaneous non-sustained ventricular tachycardia and premature ventricular contractions and their prognostic relevance in patients with cancer in routine care

AIMS: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. METHODS AND RESULTS: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction <45% were not included in the analysis. Non–sustained ventricular tachycardia (NSVT) episodes of either ≥3 and ≥4 beats duration were more frequent in cancer patients than controls (17% vs. 0%, p = 0.0008; 10% vs. 0%, p = 0.016). Premature ventricular contractions (PVCs)/24 h were not more frequent in cancer patients compared to controls (median (IQR), 26 (2–360) vs. 9 (1–43), p = 0.06; ≥20 PVCs 53% vs. 37%, p = 0.07). During follow-up, (up to 7.2 years, median 15 months) of the cancer patients, 158 (61%) died (1-/3-/5-year mortality rates: 45% [95%CI 39–51%], 66% [95%CI 59–73%], 73% [95%CI 64–82%]). Both non-sustained ventricular tachycardia of ≥4 beats and ≥20 PVCs/24 h independently predicted mortality in univariate and multivariate survival analyses, adjusted for all other univariate predictors of mortality as well as relevant clinical factors, including cancer stage and type, performance status (ECOG), prior potentially cardiotoxic anti-cancer drug therapy, coronary artery disease, potassium concentration, and haemoglobin (multivariate adjusted hazard ratios: NSVT ≥4 beats [HR 1.76, p = 0.022], ≥20 PVCs/24 h [HR 1.63, p < 0.0064]). CONCLUSIONS: NSVT ≥4 beats and ≥20 PVCs/day seen in routine 24 h ECGs of patients with cancer carry prognostic relevance

Heterologous Expression and Maturation of an NADP-Dependent [NiFe]-Hydrogenase: A Key Enzyme in Biofuel Production

Hydrogen gas is a major biofuel and is metabolized by a wide range of microorganisms. Microbial hydrogen production is catalyzed by hydrogenase, an extremely complex, air-sensitive enzyme that utilizes a binuclear nickel-iron [NiFe] catalytic site. Production and engineering of recombinant [NiFe]-hydrogenases in a genetically-tractable organism, as with metalloprotein complexes in general, has met with limited success due to the elaborate maturation process that is required, primarily in the absence of oxygen, to assemble the catalytic center and functional enzyme. We report here the successful production in Escherichia coli of the recombinant form of a cytoplasmic, NADP-dependent hydrogenase from Pyrococcus furiosus, an anaerobic hyperthermophile. This was achieved using novel expression vectors for the co-expression of thirteen P. furiosus genes (four structural genes encoding the hydrogenase and nine encoding maturation proteins). Remarkably, the native E. coli maturation machinery will also generate a functional hydrogenase when provided with only the genes encoding the hydrogenase subunits and a single protease from P. furiosus. Another novel feature is that their expression was induced by anaerobic conditions, whereby E. coli was grown aerobically and production of recombinant hydrogenase was achieved by simply changing the gas feed from air to an inert gas (N2). The recombinant enzyme was purified and shown to be functionally similar to the native enzyme purified from P. furiosus. The methodology to generate this key hydrogen-producing enzyme has dramatic implications for the production of hydrogen and NADPH as vehicles for energy storage and transport, for engineering hydrogenase to optimize production and catalysis, as well as for the general production of complex, oxygen-sensitive metalloproteins

Hand grip strength in patients with advanced cancer: a prospective study

BACKGROUND: Hand grip strength (HGS) is a widely used functional test for the assessment of strength and functional status in patients with cancer, in particular with cancer cachexia. The aim was to prospectively evaluate the prognostic value of HGS in patients with mostly advanced cancer with and without cachexia and to establish reference values for a European-based population. METHODS: In this prospective study, 333 patients with cancer (85% stage III/IV) and 65 healthy controls of similar age and sex were enrolled. None of the study participants had significant cardiovascular disease or active infection at baseline. Repetitive HGS assessment was performed using a hand dynamometer to measure the maximal HGS (kilograms). Presence of cancer cachexia was defined when patients had ≥5% weight loss within 6 months or when body mass index was <20.0 kg/m(2) with ≥2% weight loss (Fearon's criteria). Cox proportional hazard analyses were performed to assess the relationship of maximal HGS to all-cause mortality and to determine cut-offs for HGS with the best predictive power. We also assessed associations with additional relevant clinical and functional outcome measures at baseline, including anthropometric measures, physical function (Karnofsky Performance Status and Eastern Cooperative of Oncology Group), physical activity (4-m gait speed test and 6-min walk test), patient-reported outcomes (EQ-5D-5L and Visual Analogue Scale appetite/pain) and nutrition status (Mini Nutritional Assessment). RESULTS: The mean age was 60 ± 14 years; 163 (51%) were female, and 148 (44%) had cachexia at baseline. Patients with cancer showed 18% lower HGS than healthy controls (31.2 ± 11.9 vs. 37.9 ± 11.6 kg, P < 0.001). Patients with cancer cachexia had 16% lower HGS than those without cachexia (28.3 ± 10.1 vs. 33.6 ± 12.3 kg, P < 0.001). Patients with cancer were followed for a mean of 17 months (range 6-50), and 182 (55%) patients died during follow-up (2-year mortality rate 53%) (95% confidence interval 48-59%). Reduced maximal HGS was associated with increased mortality (per -5 kg; hazard ratio [HR] 1.19; 1.10-1.28; P < 0.0001; independently of age, sex, cancer stage, cancer entity and presence of cachexia). HGS was also a predictor of mortality in patients with cachexia (per -5 kg; HR 1.20; 1.08-1.33; P = 0.001) and without cachexia (per -5 kg; HR 1.18; 1.04-1.34; P = 0.010). The cut-off for maximal HGS with the best predictive power for poor survival was <25.1 kg for females (sensitivity 54%, specificity 63%) and <40.2 kg for males (sensitivity 69%, specificity 68%). CONCLUSIONS: Reduced maximal HGS was associated with higher all-cause mortality, reduced overall functional status and decreased physical performance in patients with mostly advanced cancer. Similar results were found for patients with and without cancer cachexia

Patient-reported ability to walk 4 m and to wash: New clinical endpoints and predictors of survival in patients with pre-terminal cancer

BACKGROUND: Maintaining the ability to perform self-care is a critical goal in patients with cancer. We assessed whether the patient-reported ability to walk 4 m and wash oneself predict survival in patients with pre-terminal cancer. METHODS: We performed a prospective observational study on 169 consecutive hospitalized patients with cancer (52% female, 64 ± 12 years) and an estimated 1-12 months prognosis at an academic, inpatient palliative care unit. Patients answered functional questions for 'today', 'last week', and 'last month', performed patient-reported outcomes (PROs), and physical function assessments. RESULTS: Ninety-two (54%) patients reported the ability to independently walk 4 m and 100 (59%) to wash 'today'. The median number of days patients reported the ability to walk 4 m and wash were 6 (IQR 0-7) and 7 (0-7) days ('last week'); and 27 (5-30) and 26 (10-30) days ('last month'). In the last week, 32% of patients were unable to walk 4 m on every day and 10% could walk on 1-3 days; 30% were unable to wash on every day and 10% could wash on 1-3 days. In the last months, 14% of patients were unable to walk 4 m on every day and 10% could only walk on 1-10 days; 12% were unable to wash on every day and 11% could wash on 1-10 days. In patients who could walk 'today' average 4 m gait speed was 0.78 ± 0.28 m/s. Patients who reported impaired walking and washing experienced more symptoms (dyspnoea, exertion, and oedema) and decreased physical function (higher Eastern Cooperative Oncology Group Performance Status, and lower Karnofsky Performance Status and hand-grip strength [unable vs. able to walk 'today': 205 ± 87 vs. 252 ± 78 Newton, P = 0.001; unable vs. able to wash 'today': 204 ± 86 vs. 250 ± 80 Newton, P = 0.001]). During the 27 months of observation, 152 (90%) patients died (median survival 46 days). In multivariable Cox proportional hazards regression analyses, all tested parameters were independent predictors of survival: walking 4 m 'today' (HR 0.63, P = 0.015), 'last week' (per 1 day: HR 0.93, P = 0.011), 'last month' (per 1 day: HR 0.98, P = 0.012), 4 m gait speed (per 1 m/s: HR 0.45, P = 0.002), and washing 'today' (HR 0.67, P = 0.024), 'last week (per 1 day HR 0.94, p=0.019), and 'last month' (per 1 day HR 0.99, P = 0.040). Patients unable to walk and wash experienced the shortest survival and most reduced functional status. CONCLUSIONS: In patients with pre-terminal cancer, the self-reported ability to walk 4 m and wash were independent predictors of survival and associated with decreased functional status

Clinical and prognostic relevance of cardiac wasting in patients with advanced cancer

BACKGROUND: Body wasting in patients with cancer can affect the heart. OBJECTIVES: The frequency, extent, and clinical and prognostic importance of cardiac wasting in cancer patients is unknown. METHODS: This study prospectively enrolled 300 patients with mostly advanced, active cancer but without significant cardiovascular disease or infection. These patients were compared with 60 healthy control subjects and 60 patients with chronic heart failure (ejection fraction <40%) of similar age and sex distribution. RESULTS: Cancer patients presented with lower left ventricular (LV) mass than healthy control subjects or heart failure patients (assessed by transthoracic echocardiography: 177 ± 47 g vs 203 ± 64 g vs 300 ± 71 g, respectively; P < 0.001). LV mass was lowest in cancer patients with cachexia (153 ± 42 g; P < 0.001). Importantly, the presence of low LV mass was independent of previous cardiotoxic anticancer therapy. In 90 cancer patients with a second echocardiogram after 122 ± 71 days, LV mass had declined by 9.3% ± 1.4% (P < 0.001). In cancer patients with cardiac wasting during follow-up, stroke volume decreased (P < 0.001) and resting heart rate increased over time (P = 0.001). During follow-up of on average 16 months, 149 patients died (1-year all-cause mortality 43%; 95% CI: 37%-49%). LV mass and LV mass adjusted for height squared were independent prognostic markers (both P < 0.05). Adjustment of LV mass for body surface area masked the observed survival impact. LV mass below the prognostically relevant cutpoints in cancer was associated with reduced overall functional status and lower physical performance. CONCLUSIONS: Low LV mass is associated with poor functional status and increased all-cause mortality in cancer. These findings provide clinical evidence of cardiac wasting–associated cardiomyopathy in cancer

Characteristics, Opportunities, and Challenges of Osteopathy Based on the Perceptions of Osteopaths in Austria: Qualitative Interview Study

BackgroundThere are no uniform regulations for the osteopathic profession in Europe. It is subject to country-specific regulations defining who shall be allowed to practice osteopathy and which qualification shall be required. In recent years, legal regulations have been established in several European countries for the profession of osteopathy; however, these are also still pending for Austria. Currently, physiotherapists and physicians with osteopathic training are practicing osteopathy in Austria. ObjectiveThis study aims to examine the characteristics, challenges, and opportunities of osteopaths in Austria. MethodsGuideline-based interviews with osteopaths (N=10) were conducted. The different research questions were examined using a qualitative content analysis. ResultsThe study provided a differentiated insight into the professional situation of osteopaths in Austria. The most important result was that all interviewees unanimously supported a legal regulation of their profession. However, owing to their different professional self-image—on the one hand, individuals working on a structural basis, and, on the other hand, individuals working on a cranial or biodynamic basis—they were able to imagine a uniform professional regulation only to a limited extent. Additional topics for the interviewed osteopaths in Austria were the quality assurance of training and the urgent need for scientific research. Furthermore, the study also dealt with the influence of the COVID-19 pandemic on daily practice and on education and training in osteopathy. ConclusionsThis study is a pioneering study with regard to systematic basic research on osteopathy in Austria. The obtained results and the newly acquired research questions not only have the potential to serve as a basis for further studies but also provide insight into the working and professional situation of osteopaths in Austria for universities, schools, professional associations, politics, and—last but not least—all interested parties. International Registered Report Identifier (IRRID)RR2-10.2196/1539

Quantitative magnetic force microscopy on perpendicularly magnetized samples

We present a transfer-function approach to calculate the force on a magnetic force microscope tip and the stray field due to a perpendicularly magnetized medium having an arbitrary magnetization pattern. Under certain conditions, it is possible to calculate the magnetization pattern from the measured force data. We apply this transfer function theory to quantitatively simulate magnetic force microscopy data acquired on a CoNi/Pt multilayer and on an epitaxially grown Cu/Ni/Cu/Si(001) magnetic thin film. The method described here serves as an excellent basis for (i) the definition of the condition for achieving maximum resolution in a specific experiment, (ii) the differences of force and force z-derivative imaging, (iii) the artificial distinction between domain and domain wall contrast, and finally (iv) the influence of various tip shapes on image content