Effects of vibration direction and pressing force on finger vibrotactile perception and force control

This paper reports about the effects of vibration direction and finger-pressing force on vibrotactile perception, with the goal of improving the effectiveness of haptic feedback on interactive surfaces. An experiment was conducted to assess the sensitivity to normal or tangential vibration at 250 Hz of a finger exerting constant pressing forces of 0.5 or 4.9 N. Results show that perception thresholds for normal vibration depend on the applied pressing force, significantly decreasing for the stronger force level. Conversely, perception thresholds for tangential vibrations are independent of the applied force, and approximately equal the lowest thresholds measured for normal vibration

Altering Time Perception in Virtual Reality through Multimodal Visual-tactile Kappa Effect

The perception of time is highly subjective and intertwined with space perception. In a well-known perceptual illusion, called Kappa effect, the distance between consecutive stimuli is modified to induce time distortions in the perceived inter-stimulus interval that are proportional to the distance between the stimuli. However, to the best of our knowledge, this effect has not been characterized and exploited in virtual reality (VR) within a multisensory elicitation framework. This paper investigates the Kappa effect elicited by concurrent visual-tactile stimuli delivered to the forearm, through a multimodal VR interface. This paper compares the outcomes of an experiment in VR with the results of the same experiment performed in the “physical world”, where a multimodal interface was applied to participants' forearm to deliver controlled visual-tactile stimuli. Our results suggest that a multimodal Kappa effect can be elicited both in VR and in the physical world relying on concurrent visual-tactile stimulation. Moreover, our results confirm the existence of a relation between the ability of participants in discriminating the duration of time intervals and the magnitude of the experienced Kappa effect. These outcomes can be exploited to modulate the subjective perception of time in VR, paving the path toward more personalised human-computer interaction

Validation of the Decipher Genomic Classifier in Patients receiving Salvage Radiotherapy without Hormone Therapy after Radical Prostatectomy - An Ancillary Study of the SAKK 09/10 Randomized Clinical Trial.

BACKGROUND The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase 3 trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS A clinical grade whole-transcriptome assay was performed on RP samples obtained from patients enrolled in SAKK 09/10, a phase 3 trial of 350 men with biochemical recurrence post-radical prostatectomy randomized to 64Gy vs. 70Gy without concurrent hormonal therapy or pelvic nodal radiotherapy (RT). A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, post-radical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS The analytic cohort of 226 patients was representative of the overall trial, with median follow-up of 6.3 years (IQR 6.1-7.2). GC (high vs. low-intermediate) was independently associated with biochemical progression (subdistribution hazard ratio [sHR] 2.26 [95% CI 1.42-3.60], p<0.001), clinical progression (HR 2.29 [95% CI 1.32-3.98], p=0.003), and use of hormone therapy (sHR 2.99 [95% CI 1.55-5.76], p=0.001). GC high patients had 5-year freedom from biochemical progression of 45% vs. 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower vs. higher GC scores. CONCLUSIONS This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. This data confirms the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting

Profile of sleep disturbances in patients with recurrent depressive disorder or bipolar affective disorder in a tertiary sleep disorders service

Supplementary Information is available online at https://www.nature.com/articles/s41598-023-36083-7#Sec13 .Copyright © The Author(s) 2023. Bidirectional relationship between sleep disturbances and affective disorders is increasingly recognised, but its underlying mechanisms are far from clear, and there is a scarcity of studies that report on sleep disturbances in recurrent depressive disorder (RDD) and bipolar affective disorder (BPAD). To address this, we conducted a retrospective study of polysomnographic and clinical records of patients presenting to a tertiary sleep disorders clinic with affective disorders. Sixty-three BPAD patients (32 female; mean age ± S.D.: 41.8 ± 12.4 years) and 126 age- and gender-matched RDD patients (62 female; 41.5 ± 12.8) were studied. Whilst no significant differences were observed in sleep macrostructure parameters between BPAD and RDD patients, major differences were observed in comorbid sleep and physical disorders, both of which were higher in BPAD patients. Two most prevalent sleep disorders, namely obstructive sleep apnoea (OSA) (BPAD 50.8.0% vs RDD 29.3%, P = 0.006) and insomnia (BPAD 34.9% vs RDD 15.0%, P = 0.005) were found to be strongly linked with BPAD. In summary, in our tertiary sleep clinic cohort, no overt differences in the sleep macrostructure between BPAD and RDD patients were demonstrated. However, OSA and insomnia, two most prevalent sleep disorders, were found significantly more prevalent in patients with BPAD, by comparison to RDD patients. Also, BPAD patients presented with significantly more severe OSA, and with higher overall physical co-morbidity. Thus, our findings suggest an unmet/hidden need for earlier diagnosis of those with BPAD.Wellcome Trust [103952/Z/14/Z]

Low‐carbon transition risks for finance

The transition to a low‐carbon economy will entail a large‐scale structural change. Some industries will have to expand their relative economic weight, while other industries, especially those directly linked to fossil fuel production and consumption, will have to decline. Such a systemic shift may have major repercussions on the stability of financial systems, via abrupt asset revaluations, defaults on debt, and the creation of bubbles in rising industries. Studies on previous industrial transitions have shed light on the financial transition risks originating from rapidly rising “sunrise” industries. In contrast, a similar conceptual understanding of risks from declining “sunset” industries is currently lacking. We substantiate this claim with a critical review of the conceptual and historical literature, which also shows that most literature either examines structural change in the real economy, or risks to financial stability, but rarely both together. We contribute to filling this research gap by developing a consistent theoretical framework of the drivers, transmission channels, and impacts of the phase‐out of carbon‐intensive industries on the financial system and on the feedback from the financial system into the rest of the economy. We also review the state of play of policy aiming to protect the financial system from transition risks and spell out research implications

Fstl1 Antagonizes BMP Signaling and Regulates Ureter Development

Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activity. Mouse embryos carrying disrupted Fstl1 gene displayed prominent hydroureter arising from proximal segment and ureterovesical junction defects. These defects were associated with significant reduction in ureteric epithelial cell proliferation at E15.5 and E16.5 as well as absence of subepithelial ureteral mesenchymal cells in the urinary tract at E16.5 and E18.5. At the molecular level, increased BMP signaling was found in Fstl1 deficient ureters, indicated by elevated pSmad1/5/8 activity. In vitro study also indicated that Fstl1 can directly bind to ALK6 which is specifically expressed in ureteric epithelial cells in developing ureter. Furthermore, Sonic hedgehog (SHH) signaling, which is crucial for differentiation of ureteral subepithelial cell proliferation, was also impaired in Fstl1-/- ureter. Altogether, our data suggest that Fstl1 is essential in maintaining normal ureter development by antagonizing BMP signaling

Binding between Crossveinless-2 and Chordin Von Willebrand Factor Type C Domains Promotes BMP Signaling by Blocking Chordin Activity

BACKGROUND: Crossveinless-2 (CV2) is an extracellular BMP modulator protein of the Chordin family, which can either enhance or inhibit BMP activity. CV2 binds to BMP2 via subdomain 1 of the first of its five N-terminal von Willebrand factor type C domains (VWC1). Previous studies showed that this BMP binding is required for the anti-, but not for the pro-BMP effect of CV2. More recently, it was shown that CV2 can also bind to the BMP inhibitor Chordin. However, it remained unclear which domains mediate this binding, and whether it accounts for an anti- or pro-BMP effect. PRINCIPAL FINDINGS: Here we report that a composite interface of CV2 consisting of subdomain 2 of VWC1 and of VWC2-4, which are dispensable for BMP binding, binds to the VWC2 domain of Chordin. Functional data obtained in zebrafish embryos indicate that this binding of Chordin is required for CV2's pro-BMP effect, which actually is an anti-Chordin effect and, at least to a large extent, independent of Tolloid-mediated Chordin degradation. We further demonstrate that CV2 mutant versions that per se are incapable of BMP binding can attenuate the Chordin/BMP interaction. CONCLUSIONS: We have physically dissected the anti- and pro-BMP effects of CV2. Its anti-BMP effect is obtained by binding to BMP via subdomain1 of the VWC1 domain, a binding that occurs in competition with Chordin. In contrast, its pro-BMP effect is achieved by direct binding to Chordin via subdomain 2 of VWC1 and VWC2-4. This binding seems to induce conformational changes within the Chordin protein that weaken Chordin's affinity to BMP. We propose that in ternary Chordin-CV2-BMP complexes, both BMP and Chordin are directly associated with CV2, whereas Chordin is pushed away from BMP, ensuring that BMPs can be more easily delivered to their receptors

Complex Transition to Cooperative Behavior in a Structured Population Model

Cooperation plays an important role in the evolution of species and human societies. The understanding of the emergence and persistence of cooperation in those systems is a fascinating and fundamental question. Many mechanisms were extensively studied and proposed as supporting cooperation. The current work addresses the role of migration for the maintenance of cooperation in structured populations. This problem is investigated in an evolutionary perspective through the prisoner's dilemma game paradigm. It is found that migration and structure play an essential role in the evolution of the cooperative behavior. The possible outcomes of the model are extinction of the entire population, dominance of the cooperative strategy and coexistence between cooperators and defectors. The coexistence phase is obtained in the range of large migration rates. It is also verified the existence of a critical level of structuring beyond that cooperation is always likely. In resume, we conclude that the increase in the number of demes as well as in the migration rate favor the fixation of the cooperative behavior