Clinical effectiveness of mindfulness-based music therapy on improving emotional regulation in blind older women: A randomized controlled trial.

Background: This study aimed to investigate clinical effectiveness of a structured eight-week mindfulness-based music therapy (MBMT) program on improving mood regulation in older women with blindness. This investigation compared a MBMT group with a mindfulness intervention (MI) group and a control group. Methods: Ninety-two older females with blindness from a residential setting in Hong Kong were recruited and randomly allocated to a MBMT (n = 31), MI (n = 30), or control (n = 31) group. Psychological measurements regarding mood regulation and general mood states (namely, Difficulties in Emotion Regulation Scale [DERS], Geriatric Depression Scale [GDS], and Depression Anxiety Stress Scales-21), were taken at pretest and posttest. Outcome assessors were blinded to group assignment. Results: Data was analyzed based on intention-to-treat basis. At posttest, DERS scores in the MBMT group (mean differences and 95% confidence interval: 12.1, 5.5 to 18.8) and the MI group (7.2, 0.5 to 13.8) were lower than that in the control group. GDS scores in the MBMT group (2.9, 1.7 to 4.0) and the MI group (1.7, 0.6 to 2.9) were lower than those in the control group. Compared with the MI group, the MBMT group improved emotional awareness sub-scores in DERS (2.1, 0.2 to 4.1) and appeared to lower depression in GDS scores (1.1, -0.0 to 2.3; p = 0.053). Conclusion: MBMT seems more beneficial than MI alone for improving emotional regulation in older women with blindness. The combination of mindfulness and music can generate a synergetic effect by enhancing both attention and appraisal components within the emotional-regulation process. Trial registration: ClinicalTrials.gov, NCT05583695.

A framework of interpretable match results prediction in football with FIFA ratings and team formation.

While forecasting football match results has long been a popular topic, a practical model for football participants, such as coaches and players, has not been considered in great detail. In this study, we propose a generalized and interpretable machine learning model framework that only requires coaches' decisions and player quality features for forecasting. By further allowing the model to embed historical match statistics, features that consist of significant information, during the training process the model was practical and achieved both high performance and interpretability. Using five years of data (over 1,700 matches) from the English Premier League, our results show that our model was able to achieve high performance with an F1-score of 0.47, compared to the baseline betting odds prediction, which had an F1-score of 0.39. Moreover, our framework allows football teams to adapt for tactical decision-making, strength and weakness identification, formation and player selection, and transfer target validation. The framework in this study would have proven the feasibility of building a practical match result forecast framework and may serve to inspire future studies.

Validation of the virtual-reality prospective memory test (Hong Kong Chinese version) for individuals with first-episode schizophrenia.

This study was performed to examine the psychometric properties of a Virtual-Reality Prospective Memory Test (Hong Kong Chinese version; VRPMT-CV). The VRPMT was administered to 44 individuals with first-episode schizophrenia. The test was administered again 2 weeks later to establish test-retest reliability. The concurrent validity of the VRPMT was evaluated by examining the correlations between the VRPMT score and the score on the Chinese version of the Cambridge Prospective Memory Test (CAMPROMPT-CV). The performance of individuals with schizophrenia on the VRPMT was also compared with that of 42 healthy control subjects to examine the test's sensitivity and specificity. The intraclass correlation for test-retest reliability of the total VRPMT-CV score was 0.78 (p = .005). A significant correlation was found between the total VRPMT-CV score and the total CAMPROMPT-CV score (r = 0.90; p < .001). Comparison with the healthy control subjects revealed that the total VRPMT-CV score was a sensitive (92.9%) and specific (75%) measure of prospective memory deficits in individuals with schizophrenia. The VRPMT-CV is an assessment of prospective memory that has good construct validity, test-retest reliability, sensitivity and specificity in the context of first-episode schizophrenia.

Multimodal microvascular imaging reveals that selective inhibition of class I PI3K is sufficient to induce an antivascular response.

The phosphatidylinositol 3-kinase (PI3K) pathway is a central mediator of vascular endothelial growth factor (VEGF)-driven angiogenesis. The discovery of small molecule inhibitors that selectively target PI3K or PI3K and mammalian target of rapamycin (mTOR) provides an opportunity to pharmacologically determine the contribution of these key signaling nodes in VEGF-A-driven tumor angiogenesis in vivo. This study used an array of micro-vascular imaging techniques to monitor the antivascular effects of selective class I PI3K, mTOR, or dual PI3K/mTOR inhibitors in colorectal and prostate cancer xenograft models. Micro-computed tomography (micro-CT) angiography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), vessel size index (VSI) MRI, and DCE ultrasound (DCE-U/S) were employed to quantitatively evaluate the vascular (structural and physiological) response to these inhibitors. GDC-0980, a dual PI3K/mTOR inhibitor, was found to reduce micro-CT angiography vascular density, while VSI MRI demonstrated a significant reduction in vessel density and an increase in mean vessel size, consistent with a loss of small functional vessels and a substantial antivascular response. DCE-MRI showed that GDC-0980 produces a strong functional response by decreasing the vascular permeability/perfusion-related parameter, K (trans). Interestingly, comparable antivascular effects were observed for both GDC-980 and GNE-490 (a selective class I PI3K inhibitor). In addition, mTOR-selective inhibitors did not affect vascular density, suggesting that PI3K inhibition is sufficient to generate structural changes, characteristic of a robust antivascular response. This study supports the use of noninvasive microvascular imaging techniques (DCE-MRI, VSI MRI, DCE-U/S) as pharmacodynamic assays to quantitatively measure the activity of PI3K and dual PI3K/mTOR inhibitors in vivo.

Evaluation of a computer-assisted errorless learning-based memory training program for patients with early Alzheimer's disease in Hong Kong: a pilot study.

BACKGROUND: Improving the situation in older adults with cognitive decline and evidence of cognitive rehabilitation is considered crucial in long-term care of the elderly. The objective of this study was to implement a computerized errorless learning-based memory training program (CELP) for persons with early Alzheimer's disease, and to compare the training outcomes of a CELP group with those of a therapist-led errorless learning program (TELP) group and a waiting-list control group. METHODS: A randomized controlled trial with a single-blind research design was used in the study. Chinese patients with early Alzheimer's disease screened by the Clinical Dementia Rating (score of 1) were recruited. The subjects were randomly assigned to CELP (n = 6), TELP (n = 6), and waiting-list control (n = 7) groups. Evaluation of subjects before and after testing, and at three-month follow-up was achieved using primary outcomes on the Chinese Mini-Mental State Examination, Chinese Dementia Rating Scale, Hong Kong List Learning Test, and the Brief Assessment of Prospective Memory-Short Form. Secondary outcomes were the Modified Barthel Index, Hong Kong Lawton Instrumental Activities of Daily Living Scale, and Geriatric Depression Scale-Short Form. The data were analyzed using Friedman's test for time effect and the Kruskal-Wallis test for treatment effect. RESULTS: Positive treatment effects on cognition were found in two errorless learning-based memory groups (ie, computer-assisted and therapist-led). Remarkable changes were shown in cognitive function for subjects receiving CELP and emotional/daily functions in those receiving TELP. CONCLUSION: Positive changes in the cognitive function of Chinese patients with early Alzheimer's disease were initially found after errorless training through CELP. Further enhancement of the training program is recommended.

Anti-VEGF antibody therapy does not promote metastasis in genetically engineered mouse tumour models.

Resistance to anti-angiogenic therapy can occur via several potential mechanisms. Unexpectedly, recent studies showed that short-term inhibition of either VEGF or VEGFR enhanced tumour invasiveness and metastatic spread in preclinical models. In an effort to evaluate the translational relevance of these findings, we examined the consequences of long-term anti-VEGF monoclonal antibody therapy in several well-validated genetically engineered mouse tumour models of either neuroendocrine or epithelial origin. Anti-VEGF therapy decreased tumour burden and increased overall survival, either as a single agent or in combination with chemotherapy, in all four models examined. Importantly, neither short- nor long-term exposure to anti-VEGF therapy altered the incidence of metastasis in any of these autochthonous models, consistent with retrospective analyses of clinical trials. In contrast, we observed that sunitinib treatment recapitulated previously reported effects on tumour invasiveness and metastasis in a pancreatic neuroendocrine tumour (PNET) model. Consistent with these results, sunitinib treatment resulted in an up-regulation of the hypoxia marker GLUT1 in PNETs, whereas anti-VEGF did not. These results indicate that anti-VEGF mediates anti-tumour effects and therapeutic benefits without a paradoxical increase in metastasis. Moreover, these data underscore the concept that drugs targeting VEGF ligands and receptors may affect tumour metastasis in a context-dependent manner and are mechanistically distinct from one another.

Development and validation of a fine-motor assessment tool for use with young children in a Chinese population.

OBJECTIVES: Most of the fine-motor assessment tools used in Hong Kong have been designed in Western countries, so there is a need to develop a standardized assessment which is relevant to the culture and daily living tasks of the local (that is, Chinese) population. This study aimed to (1) develop a fine-motor assessment tool (the Hong Kong Preschool Fine-Motor Developmental Assessment [HK-PFMDA]) for use with young children in a Chinese population and (2) examine the HK-PFMDA's psychometric properties. METHOD: The HK-PFMDA was developed by a group of occupational therapists specializing in the area of developmental disabilities in Hong Kong. A panel of 21 experts reviewed the content validity of the instrument. Rasch item analysis was used to examine the model fit of items against the rating scale model, and to explore the dimensionality of the test. Intra- and interrater reliability, convergent validity, and criterion-related validity were examined. The participants included 783 children without disabilities, 45 with autistic spectrum disorder, and 35 with developmental delay. RESULTS: The Rasch analysis suggested that the 87-item HK-PFMDA had a unidimensional structure, as the items explained most (91.6%) of the variance. The HK-PFMDA demonstrated excellent intra- (ICC = .99) and interrater reliability (ICC = .99), and internal consistency (α ranging from .83 to .92). In terms of validity, the HK-PFMDA had significant positive correlations with both age and the convergent measures of the Peabody Developmental Motor Scales (PDMS-2). CONCLUSION: A set of normative data for local children aged from birth to 6 years was established. The HK-PFMDA has shown excellent psychometric properties and is suitable for clinical application by occupational therapists in the assessment of fine-motor skills development of young children in Chinese populations.

Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models.

The low rate of approval of novel anti-cancer agents underscores the need for better preclinical models of therapeutic response as neither xenografts nor early-generation genetically engineered mouse models (GEMMs) reliably predict human clinical outcomes. Whereas recent, sporadic GEMMs emulate many aspects of their human disease counterpart more closely, their ability to predict clinical therapeutic responses has never been tested systematically. We evaluated the utility of two state-of-the-art, mutant Kras-driven GEMMs--one of non-small-cell lung carcinoma and another of pancreatic adenocarcinoma--by assessing responses to existing standard-of-care chemotherapeutics, and subsequently in combination with EGFR and VEGF inhibitors. Standard clinical endpoints were modeled to evaluate efficacy, including overall survival and progression-free survival using noninvasive imaging modalities. Comparisons with corresponding clinical trials indicate that these GEMMs model human responses well, and lay the foundation for the use of validated GEMMs in predicting outcome and interrogating mechanisms of therapeutic response and resistance.

Quantifying antivascular effects of monoclonal antibodies to vascular endothelial growth factor: insights from imaging.

PURPOSE: Little is known concerning the onset, duration, and magnitude of direct therapeutic effects of anti-vascular endothelial growth factor (VEGF) therapies. Such knowledge would help guide the rational development of targeted therapeutics from bench to bedside and optimize use of imaging technologies that quantify tumor function in early-phase clinical trials. EXPERIMENTAL DESIGN: Preclinical studies were done using ex vivo microcomputed tomography and in vivo ultrasound imaging to characterize tumor vasculature in a human HM-7 colorectal xenograft model treated with the anti-VEGF antibody G6-31. Clinical evaluation was by quantitative magnetic resonance imaging in 10 patients with metastatic colorectal cancer treated with bevacizumab. RESULTS: Microcomputed tomography experiments showed reduction in perfused vessels within 24 to 48 h of G6-31 drug administration (P

Directionality of the pressure-difference receiver ears in the northern leopard frog, Rana pipiens pipiens.

We studied the directional response of the coupled-eardrum system in the northern leopard frog, Rana pipiens pipiens. Eardrum behavior closely approximates a linear time-invariant system, with a highly correlated input-output relationship between the eardrum pressure difference and the eardrum velocity. Variations in the eardrum transfer function at frequencies below 800 Hz indicate the existence of an extratympanic sound transmission pathway which can interfere with eardrum motions. The eardrum velocity was shown to shift in phase as a function of sound incident angle, which was a direct result of the phase-shift of the eardrum pressure difference. We used two laser-Doppler vibrometers to measure the interaural vibration time difference (IVTD) and the interaural vibration amplitude difference (IVAD) between the motions of the two eardrums. The coupled-eardrum system enhanced the IVTD and IVAD by a factor of 3 and 3 dB, respectively, when compared to an isolated-eardrum system of the same size. Our findings are consistent with the time-delay sensitivity of other coupled-eardrum systems such as those found in crickets and flies.

Signaling mutations and autoimmunity.

Mutations in a number of signaling components in mice can lead to strong autoimmune phenotypes. In some cases, these mutations likely compromise important feedback inhibitory pathways that downregulate antigen receptor signaling. For example, a deficiency of Lyn leads to a severe lupus-like autoimmunity. This autoimmunity may result from loss of a feedback inhibitory pathway in which Lyn phosphorylates CD22, triggering recruitment of the tyrosine phosphatase SHP-1 to the plasma membrane, which then dampens BCR signaling. Loss of Lyn also compromises an inhibitory pathway involving Fc gamma RIIb and SHIP, an inositol phosphatase. Mutation of Fyn exacerbates the autoimmunity caused by loss of Lyn. This may be due in part to a nonimmunological compromise in the integrity of the podocytes in the kidney, which may make the kidneys more susceptible to immune complex-induced damage. Fyn-deficient mice exhibit a number of immunological abnormalities and also exhibit some autoimmunity, although this is less severe than what is seen in Lyn-deficient mice. Recently a gain of function mutation in CD45 that may enhance activity of Src family tyrosine kinases has also been found to cause autoimmune disease, suggesting that the level of Src family tyrosine kinase activity is an important determinant of immune tolerance. Finally, several studies suggest that there is a significant interaction between Src family tyrosine kinases and the Fas pathway that is important for self-tolerance. Although these studies are still at an early stage, it seems clear that alterations in regulators of antigen receptor signaling can contribute to autoimmunity.

Knowledge and attitudes about emergency contraception in a military population.

OBJECTIVE: To assess knowledge and attitudes about reproductive issues and emergency contraception among active duty military members. METHODS: A survey was distributed to 302 active duty members of the United States Air Force. Descriptive and Pearson chi(2) statistical analyses were used to evaluate findings. RESULTS: There was a general lack of knowledge about reproductive issues and the Yuzpe emergency contraception method. Eighty-five percent of respondents were sexually active, but only 62% used birth control. Only 40% knew when pregnancy was most likely to occur. Sixty-four percent had heard of emergency contraception, but only 15% were aware of the correct time to take it. Fifty-five percent said they would use emergency contraception if needed, with younger or unmarried individuals most willing. CONCLUSION: Knowledge deficits must be addressed to keep women deployable. Educational materials and emergency contraception kits should be standard issue items. That might prevent unwanted pregnancies and produce significant savings in reproductive health and emotional costs.