Efficacy of carboplatin-etoposide rechallenge after first-line chemo-immunotherapy in ES-SCLC: an international multicentric analysis.

Background and objectives: Second-line treatment for small-cell lung cancer (SCLC) is primarily guided by the time elapsed since the last platinum dose. Rechallenge with carboplatin and etoposide has demonstrated superior outcomes compared to topotecan if the platinum-free interval (PFI) is longer than 90 days and is considered the standard of care. However, these findings predate the chemo-immunotherapy era. This study investigates the effectiveness of the rechallenge strategy after chemo-immunotherapy in a real-world setting. Design and methods: We retrospectively reviewed patients with the extensive stage (ES)-SCLC who received rechallenge with carboplatin and etoposide after first-line chemoimmunotherapy between September 2020 and August 2023 in nine European centres. Demographic and clinical data were collected and analysed. Results: A total of 93 patients were included. Sixty-six (71%) patients had a PFI between 3 and 6 months. Consolidation thoracic radiotherapy and prophylactic cranial irradiation had been administered in 31 (33.3%) patients and 20 (21.5%) patients, respectively. Overall response rate was 59.1%. Median progression-free survival (PFS) was 5 months (95% confidence interval (CI) 4.3-5.7) and median overall survival (OS) was 7 months (95% CI 5.7-8.3). Notably, PFS and OS were not different according to PFI (3-6 m vs > 6 m). Conclusion: Rechallenge with carboplatin and etoposide is a valid second-line option in patients with ES-SCLC whose disease progresses after first-line chemoimmunotherapy. Our analysis shows similar results to previous studies. Furthermore, outcomes were consistent across patients with different PFIs, confirming its efficacy in patients with a PFI longer than 3 months.

Characterization of human placental fetal vessels in gestational diabetes mellitus.

Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.

Six years of Project ECHO: Implementation and evaluation of a hospice-led multiprofessional education programme.

Objectives: This article reports on the implementation and evaluation of an established technology-enabled collaborative learning programme (Project ECHO) at an independent UK hospice in the North of England over a 6-year period. Methods: An independent audit of collated, anonymised data from the programme is used to report attendance patterns and session evaluations. Results: The results show a gradual increase in attendances, programmes, sessions and hours of education, coupled with consistently positive evaluation reports. Conclusion: This supports existing evidence that Project ECHO is an effective method of delivering remote healthcare education, demonstrating impact on the first three levels of Moore's education framework; participation, satisfaction and learning. Future expansion in terms of geography and topics covered is proposed, alongside enhanced evaluation methods to demonstrate impact at the higher levels of Moore's framework.

Arabic within culture forensic interviews: Arabic native speaking lay-observer truth and lie accuracy, confidence, and verbal cue selection.

Cross cultural differences in behavioral and verbal norms and expectations can undermine credibility, often triggering a lie bias which can result in false convictions. However, current understanding is heavily North American and Western European centric, hence how individuals from non-western cultures infer veracity is not well understood. We report novel research investigating native Arabic speakers' truth and lie judgments having observed a matched native language forensic interview with a mock person of interest. 217 observers viewed a truthful or a deceptive interview and were directed to attend to detailedness as a veracity cue or given no direction. Overall, a truth bias (66% accuracy) emerged, but observers were more accurate (79%) in the truth condition with the truthful interviewee rated as more plausible and more believable than the deceptive interviewee. However, observer accuracy dropped to just 23% when instructed to use the detailedness cue when judging veracity. Verbal veracity cues attended too were constant across veracity conditions with 'corrections' emerging as an important veracity cue. Some results deviate from the findings of research with English speaking western participants in cross- and matched-culture forensic interview contexts, but others are constant. Nonetheless, this research raises questions for research to practice in forensic contexts centred on the robustness of western centric psychological understanding for non-western within culture interviews centred on interview protocols for amplifying veracity cues and the instruction to note detailedness of verbal accounts which significantly hindered Arabic speaker's performance. Findings again highlight the challenges of pancultural assumptions for real-world practices.

A diffusion tensor imaging white matter atlas of the domestic canine brain.

There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion-weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts-including association, projection, commissural, brainstem, olfactory, and cerebellar tracts-were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings.

A Set of FMRI Quality Control Tools in AFNI: Systematic, in-depth, and interactive QC with afni_proc.py and more.

Quality control (QC) assessment is a vital part of FMRI processing and analysis, and a typically underdiscussed aspect of reproducibility. This includes checking datasets at their very earliest stages (acquisition and conversion) through their processing steps (e.g., alignment and motion correction) to regression modeling (correct stimuli, no collinearity, valid fits, enough degrees of freedom, etc.) for each subject. There are a wide variety of features to verify throughout any single-subject processing pipeline, both quantitatively and qualitatively. We present several FMRI preprocessing QC features available in the AFNI toolbox, many of which are automatically generated by the pipeline-creation tool, afni_proc.py. These items include a modular HTML document that covers full single-subject processing from the raw data through statistical modeling, several review scripts in the results directory of processed data, and command line tools for identifying subjects with one or more quantitative properties across a group (such as triaging warnings, making exclusion criteria, or creating informational tables). The HTML itself contains several buttons that efficiently facilitate interactive investigations into the data, when deeper checks are needed beyond the systematic images. The pages are linkable, so that users can evaluate individual items across a group, for increased sensitivity to differences (e.g., in alignment or regression modeling images). Finally, the QC document contains rating buttons for each "QC block," as well as comment fields for each, to facilitate both saving and sharing the evaluations. This increases the specificity of QC, as well as its shareability, as these files can be shared with others and potentially uploaded into repositories, promoting transparency and open science. We describe the features and applications of these QC tools for FMRI.

Sleep defined by arousal threshold reveals decreases in corticocortical functional correlations independently from the conventional sleep stages.

Sleep research and sleep medicine have benefited from the use of polysomnography but have also suffered from an overreliance on the conventional, polysomnography-defined sleep stages. For example, reports of sleep-specific brain activity patterns have, with few exceptions, been constrained by assessing brain function as it relates to the conventional sleep stages. This limits the variety of sleep states and underlying activity patterns that one can discover. If undiscovered brain activity patterns exist during sleep, then removing the constraint of a stage-specific analysis may uncover them. The current study used all-night functional magnetic resonance imaging sleep data and defined sleep behaviorally with auditory arousal threshold (AAT) to begin to search for new brain states. It was hypothesized that, during sleep compared to wakefulness, corticocortical functional correlations would decrease. Functional correlation values calculated in a window immediately before the determination of AAT were entered into a linear mixed effects model, allowing multiple arousals across the night per subject into the analysis. The hypothesis was supported using both correlation matrices of brain networks and single seed-region analyses showing whole-brain maps. This represents a novel approach to studying the neuroanatomical correlates of sleep with high spatial resolution by defining sleep in a way that was independent from the conventional sleep stages. This work provides initial evidence to justify searching for sleep stages that are more neuroanatomically localized and unrelated to the conventional sleep stages.

A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach.

Immunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high-value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterized. Protein-protein interactions elevate solution viscosity in high-concentration formulations, impacting physicochemical stability, manufacturability, and the injectability of mAbs. Therefore, in this manuscript, the key molecular descriptors and biophysical properties of a model anti-IL-8 IgG1 and its IgG3 ortholog are characterized. A computational and experimental framework was applied to measure molecular descriptors impacting their downstream developability. Findings from this approach underpin a detailed understanding of the molecular characteristics of IgG3 mAbs as potential therapeutic entities. This work is the first report examining the manufacturability of IgG3 for high-concentration mAb formulations. While poorer conformational and colloidal stability and elevated solution viscosity were observed for IgG3, future efforts controlling surface potential through sequence-engineering of solvent-accessible patches can be used to improve biophysical parameters that dictate mAb developability.

Dose-dependent target engagement of a clinical iTBS protocol: An interleaved TMS-fMRI study in healthy subjects.

BACKGROUND: Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as therapeutic intervention in mental health, however understanding of its mechanisms is still incomplete. Prior MRI studies have mainly used offline iTBS or short sequences in concurrent TMS-fMRI. This study investigated a full 600 stimuli iTBS protocol using interleaved TMS-fMRI in comparison with two control conditions in healthy subjects. METHODS: In a crossover design, 18 participants underwent three sessions of interleaved iTBS-fMRI: 1) left DLPFC at 40% resting motor threshold (rMT) intensity, 2) left DLPFC at 80% rMT intensity, and 3) left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood-oxygen-level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS induced electric field (E-field) strength at the target sites. RESULTS: Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, left DLPFC, as well as bilateral M1, anterior cingulate cortex, and insula showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was not observed with 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and E-field intensities were only correlated for M1 stimulation, but not for the DLPFC conditions. CONCLUSIONS: The study showed dosage and target specific BOLD activation during interleaved TMS-fMRI with 600 stimuli iTBS in healthy subjects. Future studies may use our approach for demonstrating target engagement.

Recognising dying in motor neurone disease: A scoping review.

INTRODUCTION: Timely identification of dying in motor neurone disease enables optimal care, yet we know that healthcare professionals can fail to recognise when death is approaching. Clinical factors help predict the end of life in other terminal conditions. Examining these principles in motor neurone disease would help guide more accurate recognition of this critical phase. AIM: To examine and map out what is known about dying in patients with motor neurone disease, and the recognition of dying by healthcare professionals. DESIGN: A scoping review was conducted following the Arksey and O'Malley methodological framework. DATA SOURCES: Four electronic databases (MEDLINE, Scopus, PsycINFO and CINAHL) and grey literature were searched on the 10th May 2023. Reference lists and citations were also reviewed. RESULTS: From 1512 articles, 13 studies were included. Dyspnoea, anxiety and pain were the most common symptoms associated with the dying phase. Worsening respiratory function, the development of specific new symptoms and deteriorating symptom control suggested approaching death. No studies reported changes in vital signs or biomarkers associated with dying. Barriers to the recognition of dying by healthcare professionals included a rapid and unpredictable terminal decline. CONCLUSIONS: Dying in motor neurone disease is associated with patterns of symptoms and signs, however evidence is limited compared with other terminal conditions and requires further exploration. The characteristic sudden and unpredictable terminal decline is a key barrier to recognition of dying by healthcare professionals. Optimising advance care planning is one approach to navigate these complex, unpredictable clinical situations.

Maternal obesity and offspring cardiovascular remodelling - the effect of preconception and antenatal lifestyle interventions: a systematic review.

BACKGROUND: Preconception or antenatal lifestyle interventions in women with obesity may prevent adverse cardiovascular outcomes in the child, including cardiac remodelling. We undertook a systematic review of the existing data to examine the impact of randomised controlled trials of lifestyle interventions in pregnant women with obesity on offspring cardiac remodelling and related parameters of cardiovascular health. METHODS: This review was registered with PROSPERO (CRD42023454762) and aligns with PRISMA guidelines. PubMed, Embase, and previous reviews were systematically searched. Follow-up studies from randomised trials of lifestyle interventions in pregnant women with obesity, which included offspring cardiac remodelling or related cardiovascular parameters as outcome measures, were included based on pre-defined inclusion criteria. RESULTS: Eight studies from five randomised controlled trials were included after screening 3252 articles. Interventions included antenatal exercise (n = 2), diet and physical activity (n = 2), and preconception diet and physical activity (n = 1). Children were <2-months to 3-7-years-old, with sample sizes ranging between n = 18-404. Reduced cardiac remodelling, with reduced interventricular septal wall thickness, was consistently reported. Some studies identified improved systolic and diastolic function and a reduced resting heart rate. Risk of bias analyses rated all studies as 'fair' (some risk of bias). A high loss-to-follow-up was a common limitation. CONCLUSION: Although there is some evidence to suggest that lifestyle interventions in women with obesity may limit offspring cardiac remodelling, further high-quality longitudinal studies with larger sample sizes are required to confirm these observations and to determine whether these changes persist to adulthood. Child offspring cardiovascular health benefits of preconception and antenatal lifestyle interventions in women with obesity.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Lower resting state functional connectivity partially mediates adverse effects of prenatal alcohol exposure on arithmetic performance in children.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) include a range of neurocognitive and behavioral impairments resulting from prenatal alcohol exposure (PAE). Among the PAE-related cognitive deficits, number processing is particularly affected. This study examines alterations in number processing networks and whether changes in functional connectivity mediate the adverse effects of PAE on arithmetic performance. METHODS: Magnetic resonance imaging (MRI) was acquired in 57 children (mean (SD) age = 11.3 (+0.9) yr), 38 with FASD (19 fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 heavily exposed (HE)) and 19 controls. Whole-brain correlation analyses were performed from five seeds located in regions involved in number processing. RESULTS: Children with FAS/PFAS showed dose-dependent reductions in resting state functional connectivity between the seed in the right (R) posterior superior parietal lobule and a cluster in the left (L) inferior frontal gyrus, and between a seed in the R horizontal intraparietal sulcus and clusters in the R precentral gyrus and L cerebellar lobule VI. HE children showed lower resting state functional connectivity in a subset of these regions. Lower functional connectivity in the two fronto-parietal connections partially mediated the adverse effects of PAE on arithmetic performance. CONCLUSION: This study demonstrates PAE-related functional connectivity impairments in functional networks involved in number processing. The weaker connectivity between the R posterior superior parietal lobule and the L inferior frontal gyrus suggests that impaired verbal processing and visuospatial working memory may play a role in number processing deficits, while weaker connectivity between the R intraparietal sulcus and the R precentral gyrus points to poorer finger-based numerical representation, which has been linked to arithmetic computational skills.

Lessons learned from an fMRI-guided rTMS study on performance in a numerical Stroop task.

The Stroop task is a well-established tool to investigate the influence of competing visual categories on decision making. Neuroimaging as well as rTMS studies have demonstrated the involvement of parietal structures, particularly the intraparietal sulcus (IPS), in this task. Given its reliability, the numerical Stroop task was used to compare the effects of different TMS targeting approaches by Sack and colleagues (Sack AT 2009), who elegantly demonstrated the superiority of individualized fMRI targeting. We performed the present study to test whether fMRI-guided rTMS effects on numerical Stroop task performance could still be observed while using more advanced techniques that have emerged in the last decade (e.g., electrical sham, robotic coil holder system, etc.). To do so we used a traditional reaction time analysis and we performed, post-hoc, a more advanced comprehensive drift diffusion modeling approach. Fifteen participants performed the numerical Stroop task while active or sham 10 Hz rTMS was applied over the region of the right intraparietal sulcus (IPS) showing the strongest functional activation in the Incongruent > Congruent contrast. This target was determined based on individualized fMRI data collected during a separate session. Contrary to our assumption, the classical reaction time analysis did not show any superiority of active rTMS over sham, probably due to confounds such as potential cumulative rTMS effects, and the effect of practice. However, the modeling approach revealed a robust effect of rTMS on the drift rate variable, suggesting differential processing of congruent and incongruent properties in perceptual decision-making, and more generally, illustrating that more advanced computational analysis of performance can elucidate the effects of rTMS on the brain where simpler methods may not.

A Set of FMRI Quality Control Tools in AFNI: Systematic, in-depth and interactive QC with afni_proc.py and more.

Quality control (QC) assessment is a vital part of FMRI processing and analysis, and a typically under-discussed aspect of reproducibility. This includes checking datasets at their very earliest stages (acquisition and conversion) through their processing steps (e.g., alignment and motion correction) to regression modeling (correct stimuli, no collinearity, valid fits, enough degrees of freedom, etc.) for each subject. There are a wide variety of features to verify throughout any single subject processing pipeline, both quantitatively and qualitatively. We present several FMRI preprocessing QC features available in the AFNI toolbox, many of which are automatically generated by the pipeline-creation tool, afni_proc.py. These items include: a modular HTML document that covers full single subject processing from the raw data through statistical modeling; several review scripts in the results directory of processed data; and command line tools for identifying subjects with one or more quantitative properties across a group (such as triaging warnings, making exclusion criteria or creating informational tables). The HTML itself contains several buttons that efficiently facilitate interactive investigations into the data, when deeper checks are needed beyond the systematic images. The pages are linkable, so that users can evaluate individual items across a group, for increased sensitivity to differences (e.g., in alignment or regression modeling images). Finally, the QC document contains rating buttons for each "QC block", as well as comment fields for each, to facilitate both saving and sharing the evaluations. This increases the specificity of QC, as well as its shareability, as these files can be shared with others and potentially uploaded into repositories, promoting transparency and open science. We describe the features and applications of these QC tools for FMRI.

A study demonstrating users' preference for the adapted-REQUITE patient-reported outcome questionnaire over PRO-CTCAE® in patients with lung cancer.

Introduction: The use of patient-reported outcomes (PROs) has been shown to enhance the accuracy of symptom collection and improve overall survival and quality of life. This is the first study comparing concordance and patient preference for two PRO tools: Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) and the adapted-REQUITE Lung Questionnaire. Materials and Methods: Patients with lung cancer were recruited to the study while attending outpatient clinics at a tertiary cancer centre. Clinician-reported outcomes were generated through initial patient assessment with CTCAE v4.03. Participants then completed the PRO-CTCAE® and adapted-REQUITE questionnaires. Concordance between the 2 questionnaires was assessed by calculating Pearson correlation coefficient. PRO-CTCAE® and CTCAE concordance was demonstrated by calculating Pearson correlation coefficient from the linear predictors of an ordinal logistic regression. P-values were also calculated. Results: Out of 74 patients approached, 65 provided written informed consent to participate in the study. 63 (96.9%) patients completed both PRO-CTCAE® and adapted-REQUITE questionnaires. Pearson correlation coefficient between PRO tools was 0.8-0.83 (p <.001). Correlation between CTCAE and PRO-CTCAE® ranged between 0.66-0.82 (p <.001). Adapted-REQUITE and CTCAE correlation was higher for all symptoms ranging between 0.79-0.91 (p <.001). Acceptable discrepancies within one grade were present in 96.8%-100% of symptom domains for REQUITE and in 92.1%-96.8% for all domains in the PRO-CTCAE®. 54% of the total participant cohort favored the adapted-REQUITE questionnaire due to reduced subjectivity in the questions and ease of use. Conclusion: The adapted-REQUITE questionnaire has shown a superior correlation to clinician-reported outcomes and higher patient preference than the PRO-CTCAE®. The results of this study suggest the use of the REQUITE questionnaire for patients with lung cancer in routine clinical practice.

Mining Bodily Cues to Deception.

A significant body of research has investigated potential correlates of deception and bodily behavior. The vast majority of these studies consider discrete, subjectively coded bodily movements such as specific hand or head gestures. Such studies fail to consider quantitative aspects of body movement such as the precise movement direction, magnitude and timing. In this paper, we employ an innovative data mining approach to systematically study bodily correlates of deception. We re-analyze motion capture data from a previously published deception study, and experiment with different data coding options. We report how deception detection rates are affected by variables such as body part, the coding of the pose and movement, the length of the observation, and the amount of measurement noise. Our results demonstrate the feasibility of a data mining approach, with detection rates above 65%, significantly outperforming human judgement (52.80%). Owing to the systematic analysis, our analyses allow for an understanding of the importance of various coding factor. Moreover, we can reconcile seemingly discrepant findings in previous research. Our approach highlights the merits of data-driven research to support the validation and development of deception theory.

Belief Updating during Social Interactions: Neural Dynamics and Causal Role of Dorsomedial Prefrontal Cortex.

In competitive interactions, humans have to flexibly update their beliefs about another person's intentions in order to adjust their own choice strategy, such as when believing that the other may exploit their cooperativeness. Here we investigate both the neural dynamics and the causal neural substrate of belief updating processes in humans. We used an adapted prisoner's dilemma game in which participants explicitly predicted the coplayer's actions, which allowed us to quantify the prediction error between expected and actual behavior. First, in an EEG experiment, we found a stronger medial frontal negativity (MFN) for negative than positive prediction errors, suggesting that this medial frontal ERP component may encode unexpected defection of the coplayer. The MFN also predicted subsequent belief updating after negative prediction errors. In a second experiment, we used transcranial magnetic stimulation (TMS) to investigate whether the dorsomedial prefrontal cortex (dmPFC) causally implements belief updating after unexpected outcomes. Our results show that dmPFC TMS impaired belief updating and strategic behavioral adjustments after negative prediction errors. Taken together, our findings reveal the time course of the use of prediction errors in social decisions and suggest that the dmPFC plays a crucial role in updating mental representations of others' intentions.

TMS of the left primary motor cortex improves tremor intensity and postural control in primary orthostatic tremor.

A ponto-cerebello-thalamo-cortical network is the pathophysiological correlate of primary orthostatic tremor. Affected patients often do not respond satisfactorily to pharmacological treatment. Consequently, the objective of the current study was to examine the effects of a non-invasive neuromodulation by theta burst repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) and dorsal medial frontal cortex (dMFC) on tremor frequency, intensity, sway path and subjective postural stability in primary orthostatic tremor. In a cross-over design, eight patients (mean age 70.2 ± 5.4 years, 4 female) with a primary orthostatic tremor received either rTMS of the left M1 leg area or the dMFC at the first study session, followed by the other condition (dMFC or M1 respectively) at the second study session 30 days later. Tremor frequency and intensity were quantified by surface electromyography of lower leg muscles and total sway path by posturography (foam rubber with eyes open) before and after each rTMS session. Patients subjectively rated postural stability on the posturography platform following each rTMS treatment. We found that tremor frequency did not change significantly with M1- or dMFC-stimulation. However, tremor intensity was lower after M1- but not dMFC-stimulation (p = 0.033/ p = 0.339). The sway path decreased markedly after M1-stimulation (p = 0.0005) and dMFC-stimulation (p = 0.023) compared to baseline. Accordingly, patients indicated a better subjective feeling of postural stability both with M1-rTMS (p = 0.007) and dMFC-rTMS (p = 0.01). In conclusion, non-invasive neuromodulation particularly of the M1 area can improve postural control and tremor intensity in primary orthostatic tremor by interference with the tremor network.

Service Evaluation of MyChristie-MyHealth, an Electronic Patient-Reported Outcome Measure Integrated Into Clinical Cancer Care.

PURPOSE: Electronic patient-reported outcome measures (ePROMs) are digitalized health questionnaires used to gauge patients' subjective experience of health and disease. They are becoming prevalent in cancer care and have been linked to a host of benefits including improved survival. MyChristie-MyHealth is the ePROM established at the Christie NHS Foundation Trust in 2019. We conducted an evaluation of this service to understand user experiences, as well as strategies to improve its functioning. METHODS: Data collection: Patients who had opted never to complete MyChristie-MyHealth (n = 87), and those who had completed at least one (n = 87) were identified. Demographic data included age, sex, ethnicity, postcode, diagnosis, treatment intent, and trial status. Semistructured interviews were held with noncompleters (n = 30) and completers (n = 31) of MyChristie-MyHealth, as well as clinician users (n = 6), covering themes such as accessibility, acceptability and usefulness, and open discourse on ways in which the service could be improved. RESULTS: Noncompleters of MyChristie-MyHealth were older (median age 72 v 66 years, P = .005), receiving treatment with curative rather than palliative intent (odds ratio [OR], 1.45; P = .045), and less likely to be enrolled on a clinical trial (OR, 0.531; P = .011). They were less likely to own a smartphone (33% v 97%) or have reliable Internet access (45% v 100%). Satisfaction with MyChristie-MyHealth was high in both groups: 93% (n = 29) of completers and 87% (n = 26) noncompleters felt generally happy to complete. Completers of MyChristie-MyHealth wanted their results to be acknowledged by their clinicians. Clinicians wanted results to be displayed in a more user-friendly way. CONCLUSION: We have broadly characterized noncompleters of the Christie ePROM to identify those in need of extra support or encouragement in the clinic. An action plan resulting from this review has been compiled and will inform the future development of MyChristie-MyHealth.