Towards single-electron metrology

We review the status of the understanding of single-electron transport (SET) devices with respect to their applicability in metrology. Their envisioned role as the basis of a high-precision electrical standard is outlined and is discussed in the context of other standards. The operation principles of single electron transistors, turnstiles and pumps are explained and the fundamental limits of these devices are discussed in detail. We describe the various physical mechanisms that influence the device uncertainty and review the analytical and numerical methods needed to calculate the intrinsic uncertainty and to optimise the fabrication and operation parameters. Recent experimental results are evaluated and compared with theoretical predictions. Although there are discrepancies between theory and experiments, the intrinsic uncertainty is already small enough to start preparing for the first SET-based metrological applications.Comment: 39 pages, 14 figures. Review paper to be published in International Journal of Modern Physics

Peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy

Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy: a prospective single-centre study

Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy. To evaluate the effects of anti-tumour necrosis factor-α treatment on expression of adhesion molecules and angiogenesis in psoriatic lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab (3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4. Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI was reduced from 12.3 ± 2.4 at baseline to 1.8 ± 0.4 (P ≤ 0.02). The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 (P ≤ 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of α(v)β(3 )integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration and clinical improvement in psoriasis and psoriatic arthritis

Understanding context specificity:the effect of contextual factors on clinical reasoning

Background: Situated cognition theory argues that thinking is inextricably situated in a context. In clinical reasoning, this can lead to context specificity: a physician arriving at two different diagnoses for two patients with the same symptoms, findings, and diagnosis but different contextual factors (something beyond case content potentially influencing reasoning). This paper experimentally investigates the presence of and mechanisms behind context specificity by measuring differences in clinical reasoning performance in cases with and without contextual factors. Methods: An experimental study was conducted in 2018-2019 with 39 resident and attending physicians in internal medicine. Participants viewed two outpatient clinic video cases (unstable angina and diabetes mellitus), one with distracting contextual factors and one without. After viewing each case, participants responded to six open-ended diagnostic items (e.g. problem list, leading diagnosis) and rated their cognitive load. Results: Multivariate analysis of covariance (MANCOVA) results revealed significant differences in angina case performance with and without contextual factors [Pillai's trace = 0.72, F=12.4, df=(6, 29), p Conclusions: Using typical presentations of common diagnoses, and contextual factors typical for clinical practice, we provide ecologically valid evidence for the theoretically predicted negative effects of context specificity (i.e. for the angina case), with large effect sizes, offering insight into the persistence of diagnostic error

Functioning of patients with chronic idiopathic axonal polyneuropathy (CIAP)

Although patients with Chronic Idiopathic Axonal Polyneuropathy (CIAP) report a slow deterioration of sensory and motor functions, the impact of this deterioration on daily functioning has not yet been investigated in detail. The first aim of this crosssectional study involving 56 patients with CIAP was, therefore, to assess patients’ functioning with use of the International Classification of Functioning, Disability and Health (ICF). The second aim was to find determinants of walking ability, dexterity, and autonomy. Fatigue and limited walking ability were present in most patients and differed considerably. In regression models, age, muscle strength, and fatigue together explained 63% of the variance in walking ability, which by itself explained almost 50% of the variance in patients’ autonomy indoors and outdoors (42% and 49%, respectively). Muscle strength and sensory function scores together explained 30% of the variance in dexterity scores, which in turn explained only 13% of the variance in autonomy indoors. The diminished autonomy of patients with CIAP might be improved by reducing fatigue, by means of training, and by improving walking ability

State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease

Altres ajuts: NIH grants (ADNI U19 AG024904); UPenn (ADRC P30 AG010124); MJFox Foundation for Parkinson's Research (MJFF-005441); National Medical Research Council of Singapore; AMED grants (JP20dm0207073, JP20dm0107143); MHLW grants (19192257, 20316440); National Natural Science Foundation of China (81530036); the National Key Scientific Instrument and Equipment Development Project (31627803); Beijing Scholars Program; Beijing Brain Initiative from Beijing Municipal Science & Technology Commission (Z201100005520016, Z201100005520017); Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine; Beijing Municipal Commission of Health and Family Planning (PXM2019_026283_000003); National Key Research and Development Project grant (2017YFC1311100); Keep Memory Alive (KMA); National Institute of General Medical Sciences grant (P20GM109025); National Institute of Neurological Disorders and Stroke grant (U01NS093334); National Institute on Aging grant (R01AG053798); European Commission (Marie Curie International Training Network, Joint Programme - Neurodegenerative Disease); Health Holland; Dutch Research Council (ZonMw); the Selfridges Group Foundation; Alzheimer Netherlands; Alzheimer Association.Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD

The use of lumbar puncture and safety recommendations in Alzheimer's disease : a plain language summary

What is this summary about? This is a plain language summary of an article published in Alzheimer's & Dementia. It looks at a type of test called a lumbar puncture (also known as spinal tap) used in people suspected of having Alzheimer's disease or some other form of dementia. This summary focuses on how to do a lumbar puncture safely. Why is this important? Alzheimer's disease is a progressive condition, which means it gets worse over time. This leads to difficulties with thinking and memory. People with Alzheimer's disease show a build up of proteins called amyloid-β and tau in the brain. This is followed by a gradual loss of brain cells and brain function. The changes in the brain are thought to occur years before symptoms appear. Lumbar puncture is a medical procedure during which samples of cerebrospinal fluid are collected. In Alzheimer's disease, it is used to examine cerebrospinal fluid biomarkers that can help diagnose disease. Lumbar puncture is traditionally considered as a painful and invasive procedure with frequent side effects. However, multiple studies indicate that a lumbar puncture can be performed safely. Side effects are typically mild and do not require specialist intervention. What are the key takeaways? Despite the low risk of serious complications associated with a lumbar puncture, physicians and their patients may be reluctant to recommend or undergo this procedure. Patient education, specialist training, as well as new methods concerning patient safety are important factors to support the widespread use of lumbar puncture in Alzheimer's disease. </sec

Samenwerken en zakendoen via het Internet

In de Internetwereld zien we een nieuwe paradigma ontstaan: de ‘retailer’. Ook al is niet helemaal duidelijk wie deze rol gaat invullen, duidelijk is wel dat eindgebruikers een éénduidige ingang wensen voor een scala aan diensten. Transparantie van, onder andere, kosten is hierbij gewenst. Een dienstenaanbieder wil zich ook niet langer zorgen hoeven maken over generieke functionaliteit zoals authenticiteit en autorisatie van gebruikers, transacties, ‘application hosting’, betaling, of andere zaken die de zogenoemde retailer voor hem kan oplossen. Zo’n retailer past in een dienst-, in plaats van productgerichte aanpak. Het retailer paradigma wordt ondersteund door technische ontwikkelingen rondom het ASP model, de programmeertaal Java, ‘interoperabiliteit’, component software (hergebruik) en ‘netwerkcomputers’. Gebaseerd op het bovenstaande paradigma heeft FRIENDS een geïntegreerd platform ontwikkeld dat ondersteuning biedt aan zowel eindgebruikers, als ontwikkelaars, als aanbieders van on-line gedistribueerde diensten