Novel Straightening-Machine Design with Integrated Force Measurement for Straightening of High-Strength Flat Wire.

In a punch-bending machine, wire products are manufactured for a wide range of industrial sectors, such as the electronics industry. The raw material for this process is flat wire made of high-strength steel. During the manufacturing process of the flat wire, residual stresses and plastic deformations are induced into the wire. These residual stresses and deformations fluctuate over the length of the semi-finished product and have a negative effect on the final product quality. Straightening machines are used to reduce this influence to a minimum. So far, the adjustment of a straightening machine has been performed manually, which is a lengthy and complex task even for an experienced worker. This inevitably leads to the use of inefficient straightening strategies and causes high rejection rates in the entire production process. Due to a lack of sensor information from the straightening operation, application of modern feedback control methods has not been practicable. This paper presents a novel design for a straightening machine with an integrated, precise straightening force measurement. By simultaneously monitoring the position of the straightening rollers, state variables of the straightening operation can be derived. Additionally, a tension control for feeding the flat wire is introduced. This is implemented to mitigate the disturbing effects caused by irregularities in the wire-feeding process. In the results of this article, the high precision of the developed force measurement design and its possible applications are shown.

A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular Stroke Therapy in a Regional Stroke-Network.

BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.

Predictors of Dysphagia in Acute Pontine Infarction.

BACKGROUND AND PURPOSE: Little is known about the frequency and the clinical characteristics of neurogenic dysphagia in pontine strokes. In this study, we sought to identify predictors for dysphagia in a cohort of patients with isolated pontine infarctions. METHODS: We included all patients admitted to our department between 2008 and 2014 having an acute (<48 hours after symptom onset) ischemic stroke in the pons, as documented by means of diffusion-weighted magnetic resonance imaging. Precise infarct localization was stratified according to established vascular territories. The presence of dysphagia was the primary end point of the study and was assessed by a Speech-Language Pathologist according to defined criteria. RESULTS: The study recruited 59 patients, 14 with and 45 without dysphagia. Median (interquartile range) stroke severity (in terms of National Institutes of Health Stroke Scale values) was higher in the dysphagic group as compared with patients without dysphagia (8.5 [6-12] versus 2 [1-5]; P<0.001). Infarct localization in the upper part of the pons (78.6% versus 33.3%; P=0.004) and in the anterolateral vascular territory (78.6% versus 31.1%; P=0.002) occurred more often in the dysphagic group. In a multivariate model, age, infarct volume, and National Institutes of Health Stroke Scale value were independent predictors of dysphagia. CONCLUSIONS: Dysphagia occurs frequently in patients with isolated pontine infarctions. Clinical and imaging predictors of dysphagia may help to provide optimal screening, to prevent complications and to improve long-term prognosis.

Early Screening Parameters for Dysphagia in Acute Ischemic Stroke.

BACKGROUND: Dysphagia is a frequent symptom in patients with acute stroke. It is associated with malnutrition, aspiration and mortality. The identification of early screening parameters for dysphagia promptly leading to a professional swallowing examination is therefore of utmost importance. This study aimed to detect early and easily assessable predictors of dysphagia in a large cohort of patients with acute ischemic stroke. METHODS: Our analysis was based on data from a prospective in-hospital registry. Patients with ischemic stroke were included over the course of 3 years. Patients were scheduled to undergo a clinical swallowing investigation within the first 24 h after hospital admission. Step-wise multivariate logistic regression was used to identify independent predictors of dysphagia in general and of pneumonia in particular. RESULTS: 1,646 patients with ischemic stroke were included. Stroke severity in terms of higher National Institute of Health Stroke Scale (NIHSS) values (p < 0.001), male gender (p = 0.006) and higher age (p < 0.001) independently predicted dysphagia. A receiver operating characteristics analysis revealed an NIHSS cut-off value of 4.5 for optimal differentiation between patients with and without dysphagia (sensitivity 0.77; specificity 0.77). Dysphagia (p < 0.001), male gender (p = 0.002), higher NIHSS scores (p < 0.001) and higher age (p = 0.002) were factors that were independently associated with pneumonia. The NIHSS cut-off value for differentiating between patients with and without pneumonia was 5.5 (sensitivity 0.91; specificity 0.67). CONCLUSIONS: Stroke severity in terms of NIHSS is a simple and reliable predictor of dysphagia. Patients with NIHSS values ≥5 should be quickly directed towards a professional swallowing examination. Dysphagia was confirmed to be a strong predictor of pneumonia.

Isolated transient vertigo: posterior circulation ischemia or benign origin?

BACKGROUND: Isolated transient vertigo can be the only symptom of posterior circulation ischemia. Thus, it is important to differentiate isolated vertigo of a cerebrovascular origin from that of more benign origins, as patients with cerebral ischemia have a much higher risk for future stroke than do those with 'peripheral' vertigo. The current study aims to identify risk factors for cerebrovascular origin of isolated transient vertigo, and for future cerebrovascular events. METHODS: From the files of 339 outpatients with isolated transient vertigo we extracted history, clinical and technical findings, diagnosis, and follow-up information on subsequent stroke or transient ischemic attack (TIA). Risk factors were analyzed using multivariate regression models (logistic or Cox) and reconfirmed in univariate analyses. RESULTS: On first presentation, 48 (14.2%) patients received the diagnosis 'probable or definite cerebrovascular vertigo'. During follow-up, 41 patients suffered stroke or TIA (event rate 7.9 per 100 person years, 95% confidence interval (CI) 5.5-10.4), 26 in the posterior circulation (event rate 4.8 per 100 person years, 95% CI 3.0-6.7). The diagnosis was not associated with follow-up cerebrovascular events. In multivariate models testing multiple potential determinants, only the presentation mode was consistently associated with the diagnosis and stroke risk: patients who presented because of vertigo (rather than reporting vertigo when they presented for other reasons) had a significantly higher risk for future stroke or TIA (p = 0.028, event rate 13.4 vs. 5.4 per 100 person years) and for future posterior circulation stroke or TIA (p = 0.044, event rate 7.8 vs. 3.5 per 100 person years). CONCLUSIONS: We here report for the first time follow-up stroke rates in patients with transient isolated vertigo. In such patients, the identification of those with cerebrovascular origin remains difficult, and presentation mode was found to be the only consistent risk factor. Confirmation in an independent prospective sample is needed.

Dysphagia risk assessment in acute left-hemispheric middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. METHODS: We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. RESULTS: 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. CONCLUSIONS: In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.

Understanding the Symptoms and Impacts Experienced by People with Relapsing-Remitting MS: A Qualitative Investigation Using Semi-Structured Interviews.

INTRODUCTION: Multiple sclerosis (MS) is a disabling disease with unpredictable clinical manifestations. As clinical assessments may not fully capture the impact of MS on quality of life, they can be complemented by patient-reported outcome (PRO) measures to provide a more comprehensive picture of MS disease state and impact. The objectives of this study were to explore the experiences of people with relapsing-remitting MS, including symptoms and impacts on daily life, and to provide a conceptual model of MS outcomes. METHODS: A literature review of studies that evaluated the experiences of people with MS was completed and combined with semi-structured concept elicitation interviews conducted with 14 people with relapsing-remitting MS in the USA. RESULTS: The average age of the 14 participants was 43.9 (range 25-64) years, most were White (78.6%) and female (78.6%), and the mean duration since diagnosis was 6.6 (2-10) years. The most bothersome symptoms identified included fatigue (n = 9), cognitive dysfunction (n = 5), mobility/difficulty with walking (n = 3), and vision problems (n = 3). The most commonly reported impacts on daily life were balance problems/instability (n = 13), work life/productivity (n = 12), difficulty walking (n = 11), daily activities/household chores (n = 11), and leisure activities (n = 10). CONCLUSION: There was a high frequency of concepts associated with physical function, fatigue, and sensory-motor actions. A conceptual model was developed that captures the disease symptoms, impairments, and impacts identified in the interviews as well as known processes and symptoms identified in the literature search. This model underpins the appropriateness of PRO instruments, such as the PROMIS Fatigue (MS) 8a and PROMIS Physical Function (MS) 15a, which evaluate symptoms and impacts that matter most to people with MS.

Measuring fatigue in people with multiple sclerosis - which questionnaire should be used? A Plain Language Summary of Publication.

WHAT IS THIS SUMMARY ABOUT?: This summary explains the findings of a recent study that compared different questionnaires used by doctors to measure levels of fatigue in people with multiple sclerosis (MS). The aim of the study was to find out which questionnaire doctors should use to measure fatigue in people with MS in the future. Fatigue, which can be described as the overwhelming feeling of tiredness or exhaustion, is a very common symptom of MS. For the majority of people with MS, fatigue is one of the worst symptoms of MS, so it is essential that doctors can measure it accurately. Currently, people with MS are asked to complete questionnaires so that their care team can see the effect of fatigue on their day-to-day lives. There are many questionnaires that are used to measure fatigue in people with MS. It would be valuable to come to an agreement, based on evidence from research like this study, on which questionnaire is the most appropriate for measuring fatigue in both research and healthcare settings. This study compared a questionnaire called the PROMIS® Fatigue (MS) 8a, referred to throughout this summary as the PROMIS® MS Fatigue Short Form, with two of the most commonly used questionnaires: the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). The questionnaires were compared to see which one should be recommended to doctors for measuring fatigue in people with MS. WHAT ARE THE KEY TAKEAWAYS?: It was found that while all three questionnaires were good, the PROMIS® MS Fatigue Short Form questionnaire was better than the other two questionnaires at showing differences in levels of fatigue between people with MS. The PROMIS® MS Fatigue Short Form was also found to be better than the Fatigue Severity Scale (FSS) at showing changes in the person with MS's level of fatigue. The PROMIS® MS Fatigue Short Form questionnaire may help people with MS to better communicate challenges with their fatigue to their doctors. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: The study suggests that the PROMIS® MS Fatigue Short Form questionnaire is a helpful tool for doctors and people with MS to measure fatigue.

Paraneoplastic cerebellar degeneration associated with lymphoepithelial carcinoma of the tonsil.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a classical tumor-associated, immune-mediated disease typically associated with gynecological malignancies, small-cell lung-cancer or lymphoma. CASE PRESENTATION: Here we present the case of a 38-year old male with an over 12 months rapidly progressive cerebellar syndrome. Extensive diagnostic workup revealed selective hypermetabolism of the right tonsil in whole-body PET. Histological examination after tonsillectomy demonstrated a lymphoepithelial carcinoma of the tonsil and the tongue base strongly suggesting a paraneoplastic cause of the cerebellar syndrome. To the best of our knowledge this is the first case of an association of a lymphoepithelial carcinoma, a rare pharyngeal tumor, with PCD. CONCLUSIONS: In cases of classical paraneoplastic syndromes an extensive search for neoplasms should be performed including whole-body PET to detect tumors early in the course of the disease.

Concept for a Basic ISO 14721 Archive Information Package for Clinical Studies.

Secondary use of medical data for research is desirable for intrinsic, ethical and financial reasons. In this context, the question becomes relevant as to how such datasets are to be made accessible to a larger target group in the long term. Typically, datasets are not extracted ad hoc from the primary systems, because they are processed qualitatively (FAIR data). Special data repositories are currently being built for this purpose. This paper examines the requirements for the reuse of clinical trial data in a data repository utilizing the Open Archiving Information System (OAIS) reference model. In particular, a concept for an Archive Information Package (AIP) is developed with the central focus on a cost-effective trade-off between the effort of creation for the data producer and the comprehensibility of the data for the data consumer.

Reekeekee- and roodoodooviruses, two different Microviridae clades constituted by the smallest DNA phages.

Small circular single-stranded DNA viruses of the Microviridae family are both prevalent and diverse in all ecosystems. They usually harbor a genome between 4.3 and 6.3 kb, with a microvirus recently isolated from a marine Alphaproteobacteria being the smallest known genome of a DNA phage (4.248 kb). A subfamily, Amoyvirinae, has been proposed to classify this virus and other related small Alphaproteobacteria-infecting phages. Here, we report the discovery, in meta-omics data sets from various aquatic ecosystems, of sixteen complete microvirus genomes significantly smaller (2.991-3.692 kb) than known ones. Phylogenetic analysis reveals that these sixteen genomes represent two related, yet distinct and diverse, novel groups of microviruses-amoyviruses being their closest known relatives. We propose that these small microviruses are members of two tentatively named subfamilies Reekeekeevirinae and Roodoodoovirinae. As known microvirus genomes encode many overlapping and overprinted genes that are not identified by gene prediction software, we developed a new methodology to identify all genes based on protein conservation, amino acid composition, and selection pressure estimations. Surprisingly, only four to five genes could be identified per genome, with the number of overprinted genes lower than that in phiX174. These small genomes thus tend to have both a lower number of genes and a shorter length for each gene, leaving no place for variable gene regions that could harbor overprinted genes. Even more surprisingly, these two Microviridae groups had specific and different gene content, and major differences in their conserved protein sequences, highlighting that these two related groups of small genome microviruses use very different strategies to fulfill their lifecycle with such a small number of genes. The discovery of these genomes and the detailed prediction and annotation of their genome content expand our understanding of ssDNA phages in nature and are further evidence that these viruses have explored a wide range of possibilities during their long evolution.

Modeling the Application of IHE QRPH Profiles in Data Integration Centers: A Practical Approach with 3LGM2.

The Data Integration Centers (DICs), all part of the German Medical Informatics Initiative (MII), prepare routine care data captured in university hospitals to enable its reuse in clinical research. Tackling this challenging task requires them to maintain multiple data stores, implement the necessary transformation processes, and provide the required terminology services, all while also addressing the use case specific needs researchers might have. An MII wide application of the standardized profiles defined in the IHE QRPH domain might therefore be able to drastically reduce the overhead at any one DIC. The MII DIC reference model built in 3LGM2, a method to describe complex information system architectures, serves as a starting point to evaluate whether such an application is possible. We first extend the IHE modeling capabilities of 3LGM2 to also support the five profiles from the QRPH domain that our experts evaluated as relevant in the MII DIC context. We then expand the DIC reference model by some IHE QRPH actors and transactions, showing that their application could be beneficial in the MII DIC context, provided they surpass their trial status.

The effect of disease modifying therapies on fatigue in multiple sclerosis.

INTRODUCTION: Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard in the treatment of MS and their effectiveness has been assessed through randomized clinical trials (RCTs). However, there is limited evidence on the impact of DMTs on fatigue in (PwMS). We conducted a systematic review to 1) understand whether fatigue is included as an outcome in MS trials of DMTs; 2) determine the effects on fatigue of treating MS with DMTs and 3) assess the quality of MS trials including fatigue as an outcome. METHODS: Two independent researchers systematically searched MEDLINE, EMBASE and ClinicalTrials.gov from 1993 to January 2023 for RCTs that measured fatigue as an outcome. Adherence to reporting standards was assessed with the Consolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO), while the risk of bias (RoB) was assessed with the RoB 2 tool by the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review protocol was registered in PROSPERO (CRD42022383321). RESULTS: The search strategy identified 130 RCTs of DMTs of which 7 (5%) assessed fatigue as an outcome. Of the 7 trials, only two presented statistically significant results. In addition, the reporting of fatigue among RCTs was suboptimal with a mean adherence to the CONSORT-PRO Statement of 36% across all trials. Of the 7 trials included, four were assessed as 'high' RoB.. CONCLUSIONS: Fatigue has a major impact on PwMS yet there is limited trial-based evidence on the impact of DMTs on fatigue. Assessment of fatigue as an outcome is underrepresented in trials of DMTs and the reporting of PRO trial data is suboptimal. Thus, it is imperative that MS researchers conduct RCTs that include fatigue as an outcome, to support clinicians and people with MS (PwMS) to consider the impact of the different DMTs on fatigue.

Abundance, classification and genetic potential of Thaumarchaeota in metagenomes of European agricultural soils: a meta-analysis.

BACKGROUND: For a sustainable production of food, research on agricultural soil microbial communities is inevitable. Due to its immense complexity, soil is still some kind of black box. Soil study designs for identifying microbiome members of relevance have various scopes and focus on particular environmental factors. To identify common features of soil microbiomes, data from multiple studies should be compiled and processed. Taxonomic compositions and functional capabilities of microbial communities associated with soils and plants have been identified and characterized in the past few decades. From a fertile Loess-Chernozem-type soil located in Germany, metagenomically assembled genomes (MAGs) classified as members of the phylum Thaumarchaeota/Thermoproteota were obtained. These possibly represent keystone agricultural soil community members encoding functions of relevance for soil fertility and plant health. Their importance for the analyzed microbiomes is corroborated by the fact that they were predicted to contribute to the cycling of nitrogen, feature the genetic potential to fix carbon dioxide and possess genes with predicted functions in plant-growth-promotion (PGP). To expand the knowledge on soil community members belonging to the phylum Thaumarchaeota, we conducted a meta-analysis integrating primary studies on European agricultural soil microbiomes. RESULTS: Taxonomic classification of the selected soil metagenomes revealed the shared agricultural soil core microbiome of European soils from 19 locations. Metadata reporting was heterogeneous between the different studies. According to the available metadata, we separated the data into 68 treatments. The phylum Thaumarchaeota is part of the core microbiome and represents a major constituent of the archaeal subcommunities in all European agricultural soils. At a higher taxonomic resolution, 2074 genera constituted the core microbiome. We observed that viral genera strongly contribute to variation in taxonomic profiles. By binning of metagenomically assembled contigs, Thaumarchaeota MAGs could be recovered from several European soil metagenomes. Notably, many of them were classified as members of the family Nitrososphaeraceae, highlighting the importance of this family for agricultural soils. The specific Loess-Chernozem Thaumarchaeota MAGs were most abundant in their original soil, but also seem to be of importance in other agricultural soil microbial communities. Metabolic reconstruction of Switzerland_1_MAG_2 revealed its genetic potential i.a. regarding carbon dioxide (CO[Formula: see text]) fixation, ammonia oxidation, exopolysaccharide production and a beneficial effect on plant growth. Similar genetic features were also present in other reconstructed MAGs. Three Nitrososphaeraceae MAGs are all most likely members of a so far unknown genus. CONCLUSIONS: On a broad view, European agricultural soil microbiomes are similarly structured. Differences in community structure were observable, although analysis was complicated by heterogeneity in metadata recording. Our study highlights the need for standardized metadata reporting and the benefits of networking open data. Future soil sequencing studies should also consider high sequencing depths in order to enable reconstruction of genome bins. Intriguingly, the family Nitrososphaeraceae commonly seems to be of importance in agricultural microbiomes.

Uncovering Microbiome Adaptations in a Full-Scale Biogas Plant: Insights from MAG-Centric Metagenomics and Metaproteomics.

The current focus on renewable energy in global policy highlights the importance of methane production from biomass through anaerobic digestion (AD). To improve biomass digestion while ensuring overall process stability, microbiome-based management strategies become more important. In this study, metagenomes and metaproteomes were used for metagenomically assembled genome (MAG)-centric analyses to investigate a full-scale biogas plant consisting of three differentially operated digesters. Microbial communities were analyzed regarding their taxonomic composition, functional potential, as well as functions expressed on the proteome level. Different abundances of genes and enzymes related to the biogas process could be mostly attributed to different process parameters. Individual MAGs exhibiting different abundances in the digesters were studied in detail, and their roles in the hydrolysis, acidogenesis and acetogenesis steps of anaerobic digestion could be assigned. Methanoculleus thermohydrogenotrophicum was an active hydrogenotrophic methanogen in all three digesters, whereas Methanothermobacter wolfeii was more prevalent at higher process temperatures. Further analysis focused on MAGs, which were abundant in all digesters, indicating their potential to ensure biogas process stability. The most prevalent MAG belonged to the class Limnochordia; this MAG was ubiquitous in all three digesters and exhibited activity in numerous pathways related to different steps of AD.

Acupuncture--deep pain with an autonomic dimension?

Stimulation of acupuncture point Pc6, located above the median nerve, has been shown to be effective in treating nausea and vomiting. It has also frequently been reported to cause a heart rate reduction. The mechanism behind this autonomic reaction has not been clarified, so far. We combined brainstem-sensitive functional magnetic resonance imaging with heart rate recording and time-resolved rating of the needling sensation to measure neuronal correlates of sensations and autonomic reactions during acupuncture. On the cortical level, needling sensation activated typical pain-related areas, of which the ventromedial and dorsolateral prefrontal cortex and perigenual anterior cingulate cortex were further involved in mediating the heart rate response. In the brainstem, needling sensation activated nuclei of the descending pain control system, in which a network of hypothalamus, periaqueductal gray, rostral ventromedial medulla, and ventrolateral medulla was identified as the source of the heart rate changes. Our findings indicate that acupuncture may be a special pain stimulus, whose autonomic concomitants could explain its non-analgesic effects and in some cases even have a therapeutic potential.

A comparison of the measurement properties of the PROMIS Fatigue (MS) 8a against legacy fatigue questionnaires.

BACKGROUND: Amidst the growing number of patient-reported outcome (PRO) measures of fatigue being used in multiple sclerosis (MS) clinical trials and clinics, evidence-based consensus on the most appropriate and generalizable measures across different settings would be beneficial for clinical research and patient care. The objective of this research was to compare the validity and responsiveness of scores from the PROMIS Fatigue (MS) 8a with those of the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), across US and UK MS populations. METHODS: Two observational studies were performed in MS populations as part of a PRO measure development project, including a cross-sectional study in two tertiary US MS centers (n = 340) and a 96-week longitudinal study in the UK MS Register cohort (n = 352). In post-hoc analyses, we examined  relative validity, based on ability to discriminate across patient groups with different fatigue levels or functional status at baseline (i.e., ANOVA-F PROX ÷ ANOVA-F PROMIS (MS) 8a), and relative responsiveness, based on baseline-to-Week-52 score change (effect sizes) across fatigue or functional status response groups . RESULTS: Mean ± standard deviation (SD) age was 44.6 ± 11.3/50.0 ± 9.7; and 72.9%/77.3% were female (US/UK samples). The mean PROMIS Fatigue (MS) 8a T-score ± SD at baseline was 57.7 ± 10.5/58.9 ± 9.3 (US/UK samples). Compared with the PROMIS Fatigue (MS) 8a, relative validity (anchor: Global Health Score [GHS] fatigue global question) was 85% for MFIS symptom score, 48% for MFIS total score, and 44% for the FSS. Relative to the FSS, PROMIS Fatigue (MS) 8a scores were more sensitive to worsening (effect size = -0.43 versus -0.18) as well as improvement (effect size = 0.5 versus 0.2) in fatigue (≥1-point increase/decrease in GHS fatigue global question) over 52 weeks of follow-up. A similar pattern of score changes was observed based on a second anchor. CONCLUSION: The PROMIS Fatigue (MS) 8a scores showed higher responsiveness to fatigue changes than those of the FSS. The PROMIS measure also had higher precision in differentiating levels of fatigue compared to the FSS, the MFIS physical, and MFIS total scores. These differences have practical implications for the application of these questionnaires in both clinical practice and research settings (e.g., sample size estimation in clinical trials).

The validity, responsiveness, and score interpretation of the PROMISnq Physical Function - Multiple Sclerosis 15a short form in multiple sclerosis.

BACKGROUND: A valid, sensitive patient-reported outcome (PRO) measure of physical function (PF) for people with multiple sclerosis (MS) would have substantial value in routine care and clinical research. We now describe development of the PROMISnq Short Form v2.0 PF - Multiple Sclerosis 15a [PROMISnq PF(MS)15a] for assessing PF in relapsing and progressive MS. Also, the validity, reliability, and responsiveness of the PROMISnq PF(MS)15a is evaluated, minimal important difference (MID) thresholds for score change estimated and a score interpretation guide developed. METHODS: A mixed-methods sequential design was employed. Relevant PF concepts were elicited through semi-structured interviews with people with relapsing MS, and then mapped to the PROMIS PF item bank. Measurement experts integrated results from interviews with people with MS and input from a panel of neurologists to generate a draft short form. Relevance and comprehensiveness of the draft short form were assessed in cognitive debriefing interviews with people with relapsing or progressive MS. Subsequently, item reduction and evaluation of psychometric properties were performed in two observational studies: a cross-sectional study in the US (n = 296), and a 96-week longitudinal study in the UK MS Register cohort (n = 558). The main outcomes and measures are estimates of: known-groups validity, convergent validity, reliability, responsiveness; MID for worsening. RESULTS: Factor analyses supported the unidimensionality of the newly derived 15-item short form. Cronbach's alpha (≥ 0.97) and intraclass correlation coefficient (≥ 0.97) of test-retest scores (5-27 days) indicated strong reliability. Convergent validity was demonstrated by moderate-to-strong correlations with scores on related PRO measures. Scores discriminated among patient groups classified by levels of physical health and other criteria. Score changes of 2.3-2.7 points are proposed as MID criteria for minimal worsening in PF. CONCLUSION: PROMISnq PF(MS)15a demonstrated reliability, validity and sensitivity to change. Input from patients and clinicians ensured the content is comprehensive and relevant for people with MS.

Methodological problems in FMRI studies on acupuncture: a critical review with special emphasis on visual and auditory cortex activations.

Functional magnetic resonance imaging (fMRI) has been used for more than a decade to investigate possible supraspinal mechanisms of acupuncture stimulation. More than 60 studies and several review articles have been published on the topic. However, till now some acupuncture-fMRI studies have not adopted all methodological standards applied to most other fMRI studies. In this critical review, we comment on some of the problems including the choice of baseline, interpretation of deactivations, attention control and implications of different group statistics. We illustrate the possible impact of these problems by focussing on some early findings, namely activations of visual and auditory cortical areas, when acupoints were stimulated that are believed to have a therapeutic effect on vision or hearing in traditional Chinese medicine. While we are far from questioning the validity of using fMRI for the study of acupuncture effects, we think that activations reported by some of these studies were probably not a direct result of acupuncture stimulation but rather attributable to one or more of the methodological problems covered here. Finally, we try to offer solutions for these problems where possible.

Forgotten features of head zones and their relation to diagnostically relevant acupuncture points.

In the 1890s Sir Henry Head discovered certain areas of the skin that develop tenderness (allodynia) in the course of visceral disease. These areas were later termed "Head zones". In addition, he also emphasized the existence of specific points within these zones, that he called "maximum points", a finding that seems to be almost forgotten today. We hypothesized that two important groups of acupuncture points, the diagnostically relevant Mu and Shu points, spatially and functionally coincide with these maximum points to a large extent. A comparison of Head's papers with the Huang Di Neijing (Yellow Thearch's Inner Classic) and the Zhen Jiu Jia Yi Jing (Systematic Classic of Acupuncture and Moxibustion), two of the oldest still extant Chinese sources on acupuncture, revealed astonishing parallels between the two concepts regarding both point locations and functional aspects. These findings suggest that the Chinese discovery of viscerocutaneous reflexes preceded the discovery in the West by more than 2000 years. Furthermore, the fact that Chinese medicine uses Mu and Shu points not only diagnostically but also therapeutically may give us new insights into the underlying mechanisms of acupuncture.