Efficient Interpretation of Tandem Mass Tags in Top-Down Proteomics

Mass spectrometry is the major analytical tool for the identification and quantification of proteins in biological samples. In so-called top-down proteomics, separation and mass spectrometric analysis is performed at the level of intact proteins, without preparatory digestion steps. It has been shown that the tandem mass tag (TMT) labeling technology, which is often used for quantification based on digested proteins (bottom-up studies), can be applied in top-down proteomics as well. This, however, leads to a complex interpretation problem, where we need to annotate measured peaks with their respective generating protein, the number of charges, and the a priori unknown number of TMT-groups attached to this protein. In this work, we give an algorithm for the efficient enumeration of all valid annotations that fulfill available experimental constraints. Applying the algorithm to real-world data, we show that the annotation problem can indeed be efficiently solved. However, our experiments also demonstrate that reliable annotation in complex mixtures requires at least partial sequence information and high mass accuracy and resolution to go beyond the proof-of-concept stage

Reporting interventions in trials evaluating cognitive rehabilitation in people with Multiple Sclerosis: a systematic review

Objective: To determine the quantity and quality of description of cognitive rehabilitation for cognitive deficits in people with Multiple Sclerosis, using a variety of published checklists, and suggest ways of improving the reporting of these interventions. Data sources: Ten electronic databases were searched, including MEDLINE, EMBASE, CINAHL and PsycINFO, from inception to May 2017. Grey literature databases, trials registers, reference lists and author citations were also searched. Review methods: Papers were included if participants were people with multiple sclerosis aged 18 years and over, and if the effectiveness of cognitive rehabilitation in improving functional ability for memory, attention or executive dysfunction, with or without a control group, was being evaluated. Results: Fifty-four studies were included in this review. The reporting of a number of key aspects of cognitive rehabilitation was poor. This was particularly in relation to content of interventions (reported completely in 26 of the 54 studies), intervention procedures (reported completely in 16 of the 54 studies), delivery mode (reported completely in 24 of the 54 studies) and intervention mechanism of action (reported completely in 21 of the 54 studies). Conclusion: The quality of reporting of cognitive rehabilitation for memory, attention and executive function for multiple sclerosis, across a range of study designs, is poor. Existing reporting checklists do not adequately cover aspects relevant to cognitive rehabilitation, such as the approaches used to address cognitive deficits. Future checklists could consider these aspects we have identified in this review

Evaluation of contemporary treatment of high- and very high-risk patients for the prevention of cardiovascular events in Europe – Methodology and rationale for the multinational observational SANTORINI study

Publisher Copyright: © 2021 The AuthorsBackground and aims: Clinical practice before 2019 suggests a substantial proportion of high and very high CV risk patients taking lipid-lowering therapy (LLT) would not achieve the new LDL-C goals recommended in the 2019 ESC/EAS guidelines (<70 and < 55 mg/dL, respectively). To what extent practice has changed since the last ESC/EAS guideline update is uncertain, and quantification of remaining implementation gaps may inform health policy. Methods: The SANTORINI study is a multinational, multicentre, prospective, observational, non-interventional study documenting patient data at baseline (enrolment) and at 12-month follow-up. The study recruited 9606 patients ≥18 years of age with high and very high CV risk (as assigned by the investigators) requiring LLT, with no formal patient or comparator groups. The primary objective is to document, in the real-world setting, the effectiveness of current treatment modalities in managing plasma levels of LDL-C in high- and very high-risk patients requiring LLT. Key secondary effectiveness objectives include documenting the relationship between LLT and levels of other plasma lipids, high-sensitivity C-reactive protein (hsCRP) and overall predicted CV risk over one year. Health economics and patient-relevant parameters will also be assessed. Conclusions: The SANTORINI study, which commenced after the 2019 ESC/EAS guidelines were published, is ideally placed to provide important contemporary insights into the evolving management of LLT in Europe and highlight factors contributing to the low levels of LDL-C goal achievement among high and very high CV risk patients. It is hoped the findings will help enhance patient management and reduce the burden of ASCVD in Europe.Peer reviewe

Theory of Type-II Superconductors with Finite London Penetration Depth

Previous continuum theory of type-II superconductors of various shapes with and without vortex pinning in an applied magnetic field and with transport current, is generalized to account for a finite London penetration depth lambda. This extension is particularly important at low inductions B, where the transition to the Meissner state is now described correctly, and for films with thickness comparable to or smaller than lambda. The finite width of the surface layer with screening currents and the correct dc and ac responses in various geometries follow naturally from an equation of motion for the current density in which the integral kernel now accounts for finite lambda. New geometries considered here are thick and thin strips with applied current, and `washers', i.e. thin film squares with a slot and central hole as used for SQUIDs.Comment: 14 pages, including 15 high-resolution figure

CO 2 injection via a horizontal well into the coal seam at the Experimental Mine Barbara in Poland

This study, conducted as part of the ROCCS project, investigates the potential of coal seams for CO2 sequestration through in situ tests. The in situ tests, performed at Experimental Mine Barbara in Mikołów, Poland, involved injecting CO2 through a horizontal well into a coal seam, with variable well lengths and injection parameters. The experiments included monitoring for CO2 leakage and migration within the coal seam. The objective was to examine the correlation between the CO2 injection rate and the coal–CO2 contact area, monitoring for any potential leakage. The total mass of CO2 injected was about 7700 kg. Significant leakage, probably due to the formation of preferential pathways, prevented pressure buildup in the injection well. The results provide insights into challenges regarding CO2 injection into coal seams, with implications for the design of commercial-scale CO2 storage installations

Baby schema in human and animal faces induces cuteness perception and gaze allocation in children

The baby schema concept was originally proposed as a set of infantile traits with high appeal for humans, subsequently shown to elicit caretaking behavior and to affect cuteness perception and attentional processes. However, it is unclear whether the response to the baby schema may be extended to the human-animal bond context. Moreover, questions remain as to whether the cute response is constant and persistent or whether it changes with development. In the present study we parametrically manipulated the baby schema in images of humans, dogs, and cats. We analyzed responses of 3–6 year-old children, using both explicit (i.e., cuteness ratings) and implicit (i.e., eye gaze patterns) measures. By means of eye-tracking, we assessed children’s preferential attention to images varying only for the degree of baby schema and explored participants’ fixation patterns during a cuteness task. For comparative purposes, cuteness ratings were also obtained in a sample of adults. Overall our results show that the response to an infantile facial configuration emerges early during development. In children, the baby schema affects both cuteness perception and gaze allocation to infantile stimuli and to specific facial features, an effect not simply limited to human faces. In line with previous research, results confirm human positive appraisal toward animals and inform both educational and therapeutic interventions involving pets, helping to minimize risk factors (e.g., dog bites)

Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation

<p>Abstract</p> <p>Background</p> <p>To evaluate retrospectively the results of radiotherapy for periarthritis of the shoulder</p> <p>Methods</p> <p>In 1983–2004, 141 patients were treated, all had attended at least one follow-up examination. 19% had had pain for several weeks, 66% for months and 14% for years. Shoulder motility was impaired in 137/140 patients. Nearly all patients had taken oral analgesics, 81% had undergone physiotherapy, five patients had been operated on, and six had been irradiated. Radiotherapy was applied using regular anterior-posterior opposing portals and Co-60 gamma rays or 4 MV photons. 89% of the patients received a total dose of 6 Gy (dose/fraction of 1 Gy twice weekly, the others had total doses ranging from 4 to 8 Gy. The patients and the referring doctors were given written questionnaires in order to obtain long-term results. The mean duration of follow-up was 6.9 years [0–20 years].</p> <p>Results</p> <p>During the first follow-up examination at the end of radiotherapy 56% of the patients reported pain relief and improvement of motility. After in median 4.5 months the values were 69 and 89%, after 3.9 years 73% and 73%, respectively. There were virtually no side effects. In the questionnaires, 69% of the patients reported pain relief directly after radiotherapy, 31% up to 12 weeks after radiotherapy. 56% of the patients stated that pain relief had lasted for "years", in further 12% at least for "months".</p> <p>Conclusion</p> <p>Low-dose radiotherapy for periarthropathy of the shoulder was highly effective and yielded long-lasting improvement of pain and motility without side effects.</p

Cognitive rehabilitation in multiple sclerosis: A systematic review

Abstract Background Cognitive impairment is a common clinical feature of multiple sclerosis (MS) at both the earlier and later stages of the disease, and has a significant impact on patients' functional status and quality of life. The need to address this deficit should be taken into account in clinical practice and research studies. Objective To conduct an updated systematic review of all published studies of cognitive rehabilitation interventions in people with MS, including studies with methodological shortcomings, to highlight major strengths and weaknesses in the field and to provide directions for future research. Search methods We searched electronic databases (PubMed and Web of Science) for articles published in English up until January 2014. The reference lists of all identified articles were also searched to complete the initial list of references. Data extraction Articles were categorized into outcome measures: cognition, imaging, mood, fatigue, quality of life and self-perceived cognitive deficits. All articles were reviewed independently and assessed according to predetermined criteria. Results A total of 33 studies met the inclusion criteria of which 4 were of Level II-1 and none was Level I. Although the majority of these studies reported some improvements in cognitive abilities (N = 31), the evidence which has been reported in the literature remains inconclusive and no definite conclusions can be drawn about the effect of different types of interventions on cognitive rehabilitation outcomes (recommendation C). Conclusions This review identified conflicting findings in the published literature about the effectiveness of various forms of cognitive rehabilitation techniques used in patients with MS. Studies with more rigorous methodology are therefore needed to clarify which form of cognitive rehabilitation may lead to greater clinical improvement

Use of complementary alternative medicine for low back pain consulting in general practice: a cohort study

<p>Abstract</p> <p>Background</p> <p>Although back pain is considered one of the most frequent reasons why patients seek complementary and alternative medical (CAM) therapies little is known on the extent patients are actually using CAM for back pain.</p> <p>Methods</p> <p>This is a post hoc analysis of a longitudinal prospective cohort study embedded in a RCT. General practitioners (GPs) recruited consecutively adult patients presenting with LBP. Data on physical function, on subjective mood, and on utilization of health services was collected at the first consultation and at follow-up telephone interviews for a period of twelve months</p> <p>Results</p> <p>A total of 691 (51%) respectively 928 (69%) out of 1,342 patients received one form of CAM depending on the definition. Local heat, massage, and spinal manipulation were the forms of CAM most commonly offered. Using CAM was associated with specialist care, chronic LBP and treatment in a rehabilitation facility. Receiving spinal manipulation, acupuncture or TENS was associated with consulting a GP providing these services. Apart from chronicity disease related factors like functional capacity or pain only showed weak or no association with receiving CAM.</p> <p>Conclusion</p> <p>The frequent use of CAM for LBP demonstrates that CAM is popular in patients and doctors alike. The observed association with a treatment in a rehabilitation facility or with specialist consultations rather reflects professional preferences of the physicians than a clear medical indication. The observed dependence on providers and provider related services, as well as a significant proportion receiving CAM that did not meet the so far established selection criteria suggests some arbitrary use of CAM.</p