Beyond A/B Testing: Sequential Randomization for Developing Interventions in Scaled Digital Learning Environments

Randomized experiments ensure robust causal inference that are critical to effective learning analytics research and practice. However, traditional randomized experiments, like A/B tests, are limiting in large scale digital learning environments. While traditional experiments can accurately compare two treatment options, they are less able to inform how to adapt interventions to continually meet learners' diverse needs. In this work, we introduce a trial design for developing adaptive interventions in scaled digital learning environments -- the sequential randomized trial (SRT). With the goal of improving learner experience and developing interventions that benefit all learners at all times, SRTs inform how to sequence, time, and personalize interventions. In this paper, we provide an overview of SRTs, and we illustrate the advantages they hold compared to traditional experiments. We describe a novel SRT run in a large scale data science MOOC. The trial results contextualize how learner engagement can be addressed through inclusive culturally targeted reminder emails. We also provide practical advice for researchers who aim to run their own SRTs to develop adaptive interventions in scaled digital learning environments

On the Elevated Temperature Thermal Stability of Nanoscale Mn-Ni-Si Precipitates Formed at Lower Temperature in Highly Irradiated Reactor Pressure Vessel Steels.

Atom probe tomography (APT) and scanning transmission electron microscopy (STEM) techniques were used to probe the long-time thermal stability of nm-scale Mn-Ni-Si precipitates (MNSPs) formed in intermediate and high Ni reactor pressure vessel steels under high fluence neutron irradiation at ≈320 °C. Post irradiation annealing (PIA) at 425 °C for up to 57 weeks was used to determine if the MNSPs are: (a) non-equilibrium solute clusters formed and sustained by radiation induced segregation (RIS); or, (b) equilibrium G or Γ2 phases, that precipitate at accelerated rates due to radiation enhanced diffusion (RED). Note the latter is consistent with both thermodynamic models and x-ray diffraction (XRD) measurements. Both the experimental and an independently calibrated cluster dynamics (CD) model results show that the stability of the MNSPs is very sensitive to the alloy Ni and, to a lesser extent, Mn content. Thus, a small fraction of the largest MNSPs in the high Ni steel persist, and begin to coarsen at long times. These results suggest that the MNSPs remain a stable phase, even at 105 °C higher than they formed at, thus are most certainly equilibrium phases at much lower service relevant temperatures of ≈290 °C

Atom probe characterisation of segregation driven Cu and Mn-Ni-Si co-precipitation in neutron irradiated T91 tempered-martensitic steel

The T91 grade and similar 9Cr tempered-martensitic steels (also known as ferritic-martensitic) are leading candidate structural alloys for fast fission nuclear and fusion power reactors. At low temperatures (300 to 400 $^\circ$C) neutron irradiation hardens and embrittles these steels, therefore it is important to investigate the origin of this mode of life limiting property degradation. T91 steel specimens were separately neutron irradiated to 2.14 dpa at 327 $^\circ$C and 8.82 dpa at 377 $^\circ$C in the Idaho National Laboratory Advanced Test Reactor. Atom probe tomography was used to investigate the segregation driven formation of Mn-Ni-Si-rich (MNSPs) and Cu-rich (CRP) co-precipitates. The precipitates increase in size and, slightly, in volume fraction at the higher irradiation temperature and dose, while their corresponding compositions were very similar, falling near the Si(Mn,Ni) phase field in the Mn-Ni-Si projection of the Fe-based quaternary phase diagram. While the structure of the precipitates has not been characterized, this composition range is distinctly different than that of the typically cited G-phase. The precipitates are composed of CRP with MNSP appendages. Such features are often observed in neutron irradiated reactor pressure vessel (RPV) steels. However, the Si, Ni, Mn, P and Cu solutes concentrations are lower in the T91 than in typical RPV steels. Thus, in T91 precipitation primarily takes place in solute segregated regions of line and loop dislocations. These results are consistent with the model for radiation induced segregation driven precipitation of MNSPs proposed by Ke et al. Cr-rich alpha prime ($\alpha$') phase formation was not observed.Comment: Pre-print (not peer reviewed

Glycaemia Fluctuations Improvement in Old-Age Prediabetic Subjects Consuming a Quinoa-Based Diet: A Pilot Study

This study aimed to observe if quinoa could produce a benefit on postprandial glycemia that would result in less progression to type 2 diabetes (T2D). A cross-over design pilot clinical study with a nutritional intervention for 8 weeks was performed: 4 weeks on a regular diet (RD) and 4 weeks on a quinoa diet (QD). Nine subjects aged ?65 years with prediabetes were monitored during the first 4 weeks of RD with daily dietary records and FreeStyle Libre®. Subsequently, participants started the QD, where quinoa and 100% quinoa-based products replaced foods rich in complex carbohydrates that they had consumed in the first 4 weeks of RD. The glycemic measurements recorded by the sensors were considered as functions of time, and the effects of nutrients consumed at the intended time period were analyzed by means of a function-on-scalar regression (fosr) model. With QD participants, decreased body weight (-1.6 kg, p = 0.008), BMI (-0.6 kg/m2p = 0.004) and waist circumference (-1.5 cm, p = 0.015) were observed. Nutrients intake changed during QD, namely, decreased carbohydrates (p = 0.004) and increased lipids (p = 0.004) and some amino acids (p < 0.05). The fosr model showed a reduction in postprandial glycemia in QD despite intrapersonal differences thanks to the joint action of different nutrients and the suppression of others consumed on a regular diet. We conclude that in an old age and high T2D-risk population, a diet rich in quinoa reduces postprandial glycemia and could be a promising T2D-preventive strategy

Practical guidelines for the early diagnosis of Sjogren's syndrome in primary healthcare

Primary care physicians can play a crucial role by recognising Sjogren's syndrome (SS) in the early stages identifying those patients with the greatest probability of being diagnosed with SS. SS has a very specific epidemiological profile at presentation (female aged 3050 years), which may aid an early diagnosis. Although the disease may be expressed in many guises, there are three predominant clinical presentations that should be considered as key clues to increased clinical suspicion (multiple symptoms of dryness, asthenia-polyalgia syndrome and systemic organ-specific manifestations). The physical examination may provide important clues to systemic involvement (parotid gland enlargement, skin lesions suggestive of purpura or annular erythema, respiratory crackles, arthritis, neurological sensory or motor deficits). Simple laboratory studies may be very useful in reinforcing the clinical suspicion of SS, and the triad of cytopenia, raised erythrocyte sedimentation rate and high serum gamma globulin levels is a very specific "biological" pattern suggesting SS. A solid clinical suspicion of SS requires both the patient reporting sicca symptoms and objective evidence that these symptoms are associated with dysfunction of the lachrymal and salivary glands. Ultrasonography of the parotid glands, a non-invasive method, may be a major advance in the diagnostic approach to SS in primary care. Primary care physicians must be considered essential members of the multidisciplinary team in charge of the follow-up of SS patients, due to their key role in the continuum of patient care and their cross-sectional knowledge of common diseases that frequently coexist in patients with SS.</p

Effectiveness of a Multicomponent Treatment based on Pain Neuroscience Education, Therapeutic Exercise, Cognitive Behavioural Therapy, and Mindfulness in Patients with Fibromyalgia (FIBROWALK study) : A Randomized Controlled Trial

Methods. A randomised controlled trial (RCT) was carried out to evaluate the effectiveness of a 12-week multicomponent treatment based on pain neuroscience education, therapeutic exercise, cognitive behavioural therapy and mindfulness, in addition to treatment as usual (TAU), compared to TAU only in patients with fibromyalgia (FM). The multicomponent treatment (2h weekly sessions) was delivered in groups of 20 participants. TAU was mainly based on pharmacotherapy. We collected data on functional impairment (the Revised Fibromyalgia Impact Questionnaire [FIQR], as primary outcome), pain, fatigue, kinesiophobia, physical function, anxiety, and depressive symptoms (secondary outcomes) at baseline, at 12 weeks and, for the multicomponent group only, at 6 and 9 months. An intention to treat approach was used to analyse between-group differences. We also analysed baseline differences between responders (> 20% FIQR reduction) and non-responders and computed the number needed to treat (NNT). Results. A total of 272 patients with FM were randomly assigned to either the multicomponent treatment (n = 135) or TAU (n = 137). Significant between-group differences (p .80) were found for functional impairment, pain, kinesiophobia, and physical function, whilst differences with a moderate size effect (Cohen's d > 0.50 and < 0.80) were found for fatigue, anxiety, and depressive symptoms. Non-responders scored higher on depressive symptoms than responders at baseline. The number needed to treat was 2 (95% CI 1.7 - 2.3). Conclusions. Our results indicate that, when compared to TAU, the multicomponent treatment was effective for improving FM-related symptoms. Nevertheless, we must temper our findings in light of some methodological limitations in the study design. Impact statement. This is the first RCT showing positive effects on a wide range of clinical outcomes of a multicomponent treatment that integrates pain neuroscience education for patients with fibromyalgia. This work reports promising results and it might be the first step towards a paradigm shift in the management of fibromyalgia

Proof of concept of a treatment for fibromyalgia based on physical activity, psychological support, and exposure to nature (NAT-FM)

Aim: To provide a preliminary assessment of the efficacy of the NAT-FM protocol as a complimentary treatment in patients with fibromyalgia (FM). Methods: A trial was conducted, with two arms: TAU (n = 6) and TAU+NAT-FM (n = 6). Results: There was a reduction in physical limitations and anxious/depressive symptoms and an improvement in positive affect in the intervention group. Also, this group showed a decrease in pain, catastrophizing, negative affect, and positively refocusing, and an increase in positive affect. Intrasession assessments showed an increase in positive affect, self-efficacy, and energy, along with a decrease in stress. Intersession assessments revealed an increase in pain, valence, and dominance. Conclusion: The results suggest the appropriateness of the NAT-FM protocol

Effectiveness of a Multicomponent treatment for fibromyalgia based on Pain neuroscience education, Exercise therapy, Psychological support, and Nature exposure (NAT-FM): A Pragmatic randomized controlled trial

A recent study (FIBROWALK) has supported the effectiveness of a multicomponent treatment based on pain neuroscience education (PNE), exercise therapy (TE), cognitive behavioral therapy (CBT), and mindfulness in patients with fibromyalgia. The aim of the present RCT was: (a) to analyze the effectiveness of a 12-week multicomponent treatment (nature activity therapy for fibromyalgia, NAT-FM) based on the same therapeutic components described above plus nature exposure to maximize improvements in functional impairment (primary outcome), as well as pain, fatigue, anxiety-depression, physical functioning, positive and negative a ect, self-esteem, and perceived stress (secondary outcomes), and kinesiophobia, pain catastrophizing thoughts, personal perceived competence, and cognitive emotion regulation (process variables) compared with treatment as usual (TAU); (b) to preliminarily assess the e ects of the nature-based activities included (yoga, Nordic walking, nature photography, and Shinrin Yoku); and (c) to examine whether the positive effects of TAU + NAT-FM on primary and secondary outcomes at post-treatment were mediated through baseline to six-week changes in process variables. A total of 169 FM patients were randomized into two study arms: TAU + NAT-FM vs. TAU alone. Data were collected at baseline, at six-week of treatment, at post-treatment, and throughout treatment by ecological momentary assessment (EMA). Using an intention to treat (ITT) approach, linear mixed-e ects models and mediational models through path analyses were computed. Overall, TAU + NAT-FM was significantly more e ective than TAU at posttreatment for the primary and secondary outcomes evaluated, as well as for the process variables. Moderate-to-large effect sizes were achieved at six-weeks for functional impairment, anxiety, kinesiophobia, perceived competence, and positive reappraisal. The number needed to treat (NNT) was 3 (95%CI = 1.6-3.2). The nature activities yielded an improvement in affective valence, arousal, dominance, fatigue, pain, stress, and self-effcacy. Kinesiophobia and perceived competence were the mediators that could explain a significant part of the improvements obtained with TAU + NAT-FM treatment. TAU + NAT-FM is an e ective co-adjuvant multicomponent treatment for improving FM-related symptoms

Sacroiliac joint radiographic progression - speed and determinants

Non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axial spondyloarthritis (r-axSpA) are considered to be different spectra of the same disease. Accumulating data suggest a low transition rate from nr-axSpA to r-axSpA in patients with early disease and identify inflammation, smoking and HLA-B27 positivity as factors associated with transition