Impact of Marginal Exciton-Charge-Transfer State Offset on Charge Generation and Recombination in Polymer:Fullerene Solar Cells

The energetic offset between the initial photoexcited state and charge-transfer (CT) state in organic heterojunction solar cells influences both charge generation and open-circuit voltage (Voc). Here, we use time-resolved spectroscopy and voltage loss measurements to analyze the effect of the exciton–CT state offset on charge transfer, separation, and recombination processes in blends of a low-band-gap polymer (INDT-S) with fullerene derivatives of different electron affinity (PCBM and KL). For the lower exciton–CT state offset blend (INDT-S:PCBM), both photocurrent generation and nonradiative voltage losses are lower. The INDT-S:PCBM blend shows different excited-state dynamics depending on whether the donor or acceptor is photoexcited. Surprisingly, the charge recombination dynamics in INDT-S:PCBM are distinctly faster than those in INDT-S:KL upon excitation of the donor. We reconcile these observations using a kinetic model and by considering hybridization between the lowest excitonic and CT states. The modeling results show that this hybridization can significantly reduce Voc losses while still allowing reasonable charge generation efficiency

The Relationship between ECOG-PS, mGPS, BMI/WL Grade and Body Composition and Physical Function in Patients with Advanced Cancer

Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p < 0.001), low skeletal muscle density (p < 0.05), and timed up and go test failure (p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p < 0.05) and hand grip strength test failure (p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p < 0.05), low visceral obesity (p < 0.01), and low skeletal muscle density (p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer

The Italian language postpartum specific anxiety scale [PSAS-IT]: translation, psychometric evaluation, and validation.

Introduction: While often positive, the lifecourse transition to motherhood is susceptible to the risk for developing mood disorders. Postpartum anxiety has often been overshadowed by other perinatal-specific mental health disorders, such as postpartum depression, and therefore has not been at the forefront or center of as much empirical study. This has meant there is a lack of effective and reliable tools with which to measure it, despite growing evidence suggesting its detrimental impact on mothers, their babies, wider family and social contacts, and on healthcare systems. This current study aimed to translate and validate the Postpartum Specific Anxiety Scale [PSAS] into the Italian language, and to validate the tool for its use in detecting anxiety specific to motherhood. Methods: The study (N = 457) comprised 4 stages: English-Italian translation and back-translation to obtain the Italian version [PSAS-IT]; a preliminary pilot study to adapt the PSAS to the characteristics of the Italian population; measurement invariance; and internal reliability of subscales. Results: The PSAS-IT demonstrates similar psychometric properties as the original English-language PSAS, with acceptable acceptability, construct and convergent validity, and internal consistency. Confirmatory factor analysis for multiple groups (Italy and United Kingdom) showed that the factor structure of the PSAS was valid for both groups [χ2 (2436) = 4679.481, p < 0.001, TLI = 0.969, CFI =0.972, RMSEA = 0.045, SRMR =0.064]. Discussion: The resulting findings offer a reliable measure of postpartum anxiety in Italian language up to six months after birth

Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation

Natural killer (NK) cells are innate lymphocytes that provide early host defense against intracellular pathogens, such as viruses. Although NK cell development, homeostasis, and proliferation are regulated by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not been quantitatively characterized. We developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Our computational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. Ligand binding and receptor internalization modulated IL-15R occupancy. Our work supports the hypothesis that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitative threshold prior to the initiation of NK cell division. Furthermore, our model predicted that the upregulation of IL-15Rα on NK cells substantially increased IL-15R complex formation and accelerated the expansion of dividing NK cells with the greatest impact at low IL-15 concentrations. Model predictions of the threshold requirement for NK cell recruitment to the cell cycle and the subsequent exponential proliferation correlated well with experimental data. In summary, our modeling analysis provides quantitative insight into the regulation of NK cell proliferation at the receptor level and provides a framework for the development of IL-15 based immunotherapies to modulate NK cell proliferation

Postpartum-specific anxiety as a predictor of infant-feeding outcomes and perceptions of infant-feeding behaviours: new evidence for childbearing specific measures of mood

Studies of pregnancy-specific anxiety suggest that it is a distinct construct which predicts perinatal outcomes more effectively than other general measures of anxiety. In response, a novel measure of postpartum-specific anxiety (PSAS) has been developed and validated, but it is not yet clear whether it possesses the same predictive power as its pregnancy-specific counterparts. The aim of this short-term prospective study was to (a) test the predictive validity of the PSAS in the context of one specific perinatal outcome, infant-feeding, and (b) examine whether the PSAS may be more efficacious at predicting infant-feeding outcomes and behaviours than the more commonly used general measures. Eight hundred mothers of infants aged between 0 and 6 months completed the PSAS alongside general measures of anxiety and depression at baseline. A subsample (n = 261) returned to complete a follow-up questionnaire examining infant-feeding outcomes and behaviours two weeks later. Hierarchical regression models revealed that the PSAS was associated with lower odds of breastfeeding exclusively, and breastfeeding in any quantity in the first 6 months postpartum. PSAS scores were also significantly associated with infant-feeding behaviours including a lower perceived enjoyment of food, and greater perceived food responsiveness and satiety responsiveness in the infant. As hypothesised, the PSAS was a stronger predictor of infant-feeding outcomes and behaviours than general anxiety and depression. The findings provide evidence for the predictive validity of the PSAS and call for the use of childbearing specific measures of mood when attempting to predict perinatal outcomes. Replication of these findings across other indices of maternal and infant health is now necessary

Malignant spinal cord compression: a retrospective audit of clinical practice at a UK regional cancer centre

Malignant Spinal Cord Compression (MSCC) is a particularly challenging area of cancer care where early diagnosis and expert multiprofessional care and rehabilitation, are paramount in optimising quality of life. This audit reports data collected retrospectively over a period of 12 months on patients with MSCC referred to the West of Scotland Cancer Centre (n=174). It was carried out to build on the work of the Clinical Resource and Audit Group (CRAG) and to examine current practice for symptom assessment, multiprofessional care and rehabilitation of patients with MSCC admitted to the cancer centre. Areas of concern include poor assessment of pain, the poor ambulatory status of patients on admission and the lack of clear plans for mobilisation and rehabilitation for the majority of patients. Recommendations include the development of regional guidelines for referral, treatment and rehabilitation, and the development of a pathway of care for use in all care settings across the region, together with improvements for use in patient information, staff education, audit and research. These are now being taken forward through the West of Scotland Cancer Network with dedicated funding from Macmillan Cancer Relief

Quality of life endpoints in cancer cachexia clinical trials: Systematic review 3 of the cachexia endpoints series.

The use of patient-reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self-report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990-2023). Seven thousand four hundred thirty-five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full-text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty-four (48%) were double-blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty-nine trials (78%) included multiple cancer types. Twenty-seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4-96). The most frequent QOL measure was the EORTC QLQ-C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well-validated QOL measures, including cachexia-specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co-primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific-based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures

Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome

Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS. Methods and Principal Findings: Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p&0.01). CFS (n = 43) had 2,783 non-redundant proteins, nPTLS (n = 25) contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes. Conclusions: nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions

Triceps Surae Short Latency Stretch Reflexes Contribute to Ankle Stiffness Regulation during Human Running

During human running, short latency stretch reflexes (SLRs) are elicited in the triceps surae muscles, but the function of these responses is still a matter of controversy. As the SLR is primarily mediated by Ia afferent nerve fibres, various methods have been used to examine SLR function by selectively blocking the Ia pathway in seated, standing and walking paradigms, but stretch reflex function has not been examined in detail during running. The purpose of this study was to examine triceps surae SLR function at different running speeds using Achilles tendon vibration to modify SLR size. Ten healthy participants ran on an instrumented treadmill at speeds between 7 and 15 km/h under 2 Achilles tendon vibration conditions: no vibration and 90 Hz vibration. Surface EMG from the triceps surae and tibialis anterior muscles, and 3D lower limb kinematics and ground reaction forces were simultaneously collected. In response to vibration, the SLR was depressed in the triceps surae muscles at all speeds. This coincided with short-lasting yielding at the ankle joint at speeds between 7 and 12 km/h, suggesting that the SLR contributes to muscle stiffness regulation by minimising ankle yielding during the early contact phase of running. Furthermore, at the fastest speed of 15 km/h, the SLR was still depressed by vibration in all muscles but yielding was no longer evident. This finding suggests that the SLR has greater functional importance at slow to intermediate running speeds than at faster speeds