Prothrombin time (PT) and the associated international normalized ratio (INR) are routinely tested to assess the risk of bleeding or thrombosis and to monitor response to anticoagulant therapy in ...patients. To measure PT/INR, conventional coagulation testing (CCT) is performed, which is time-consuming and requires the separation of cellular components from whole blood. Here, we report on a portable and battery-operated optical sensor that can rapidly quantify PT/INR within seconds by measuring alterations in the viscoelastic properties of a drop of whole blood following activation of coagulation with thromboplastin. In this study, PT/INR values were measured in 60 patients using the optical sensor and compared with the corresponding CCT values. Our results report a close correlation and high concordance between PT/INR measured using the two approaches. These findings confirm the accuracy of our optical sensing approach for rapid PT/INR testing in whole blood and highlight the potential for use at the point-of-care or for patient self-testing.
This paper examines the health-related quality of life (HRQL) and mental health of adolescent young carers (AYCs) aged 15-17 in Switzerland, based on data collected within the Horizon 2020 project ...'Psychosocial support for promoting mental health and well-being among AYCs in Europe' (ME-WE). It addresses the following questions: (1) Which characteristics of AYCs are associated with lower HRQL and with higher level of mental health problems? (2) Do AYCs who are less visible and less supported report a lower HRQL and more mental health issues than other AYCs? A total of 2343 young people in Switzerland, amongst them 240 AYCs, completed an online survey. The results show that female AYCs and AYCs with Swiss nationality more often reported having mental health issues than their male and non-Swiss counterparts. Furthermore, the findings show a significant association between receiving support for themselves and visibility from their school or employer and the HRQL. Moreover, AYCs who reported that their school or employer knew about the situation also reported fewer mental health issues. These findings can inform recommendations for policy and practice to develop measures aimed at raising the visibility of AYCs, which is the first step for planning AYC tailored support.
The Careum Summer School (CSS) is a learning setting that enables self-regulated learning in an environment in which trainees and students from the various medical, nursing and therapeutic healthcare ...professions taught in the Swiss education system (upper secondary and tertiary levels A and B) develop project ideas together with patients and their caregivers. The aim of this learning setting is to promote a positive attitude among trainees and students towards interprofessional collaboration that includes patients as cooperation partners.
The evaluation examines the extent to which trainees' and students' attitudes towards interprofessional collaboration changed. Information was also obtained on the experiences patients and their caregivers had during their participation in the CSS programme.
A total of 69 trainees and students were given access to an online survey in the form of the German version of the University of the West of England Interprofessional Questionnaire (UWE-IP) one week before the CSS programme began and six weeks after it concluded. Problem-focused interviews were also conducted with 11 patients and their caregivers.
The attitudes of the trainees and students in the UWE-IP Interprofessional Learning Scale improved significantly after the CSS programme was conducted (median t1=22.0/t2=16.0). The effect size was r=0.839 (Wilcoxon test for dependent samples). No significant results could be identified for the other three UWE-IP scales. Patients and their caregivers reported that they were able to actively participate in the CSS programme and felt valued and appreciated.
The CSS offered a learning environment in which all participants were able to exchange knowledge and information in an interprofessional manner and work collaboratively on the development of a project idea - for example an interprofessional competency passport with a spider diagram.
Young carers provide a substantial amount of care to family members and support to friends, yet their situation has not been actively addressed in research and policy in many European countries or ...indeed globally. Awareness of their situation by professionals and among children and young carers themselves remains low overall. Thus, young carers remain a largely hidden group within society. This study reports and analyses the recruitment process in a multi-centre intervention study offering psychosocial support to adolescent young carers (AYCs) aged 15-17 years. A cluster-randomised controlled trial was designed, with recruitment taking place in Italy, the Netherlands, Slovenia, Sweden, Switzerland and the United Kingdom exploiting various channels, including partnerships with schools, health and social services and carers organisations. In total, 478 AYCs were recruited and, after screening failures, withdrawals and initial dropouts, 217 were enrolled and started the intervention. Challenges encountered in reaching, recruiting and retaining AYCs included low levels of awareness among AYCs, a low willingness to participate in study activities, uncertainty about the prevalence of AYCs, a limited school capacity to support the recruitment; COVID-19 spreading in 2020-2021 and related restrictions. Based on this experience, recommendations are put forward for how to better engage AYCs in research.
Results from electrochemical studies, in situ STM, and ex situ angle-resolved XPS on self-assembled monolayers (SAMs) of thiazole on Au(111) are reported for the first time. Although STM seems to ...indicate a low density of molecules organized in small ordered domains, a quantitative chemical analysis of the sample surface by XPS clearly points toward the formation of a densely packed molecular layer. The stability of the thiazole SAM against reductive desorption is found to be very comparable with that for thiol-SAMs on gold. This results from the formation of Au−S bonds between the molecules and their support as evidenced by XPS, thereby rebuting speculations that the ring nitrogen is responsible for the attachment of such molecules to gold surfaces. Consequently, the N-atoms terminating the molecular layer are available as active sites for the complexation with Pd ions thereby allowing the deposition of Pd islands with monatomic height on top of the thiazole SAM. The importance of such studies for metal−molecule interconnections is briefly addressed.
Humans modify ecosystems and biodiversity worldwide, with negative consequences for ecosystem functioning. Promoting plant diversity is increasingly suggested as a mitigation strategy. However, our ...mechanistic understanding of how plant diversity affects the diversity of heterotrophic consumer communities remains limited. Here, we disentangle the relative importance of key components of plant diversity as drivers of herbivore, predator, and parasitoid species richness in experimental forests and grasslands. We find that plant species richness effects on consumer species richness are consistently positive and mediated by elevated structural and functional diversity of the plant communities. The importance of these diversity components differs across trophic levels and ecosystems, cautioning against ignoring the fundamental ecological complexity of biodiversity effects. Importantly, plant diversity effects on higher trophic-level species richness are in many cases mediated by modifications of consumer abundances. In light of recently reported drastic declines in insect abundances, our study identifies important pathways connecting plant diversity and consumer diversity across ecosystems.
The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane ...insertion of β-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment. The precursor is translocated into the channel interior, interacts with an internal loop, and inserts into the lateral gate by β-signal exchange. Transport through the Omp85-channel interior followed by release through the lateral gate into the lipid phase may represent a basic mechanism for membrane insertion of β-barrel proteins.
Protein kinase C (PKC) isozymes have remained elusive cancer targets despite the unambiguous tumor promoting function of their potent ligands, phorbol esters, and the prevalence of their mutations. ...We analyzed 8% of PKC mutations identified in human cancers and found that, surprisingly, most were loss of function and none were activating. Loss-of-function mutations occurred in all PKC subgroups and impeded second-messenger binding, phosphorylation, or catalysis. Correction of a loss-of-function PKCβ mutation by CRISPR-mediated genome editing in a patient-derived colon cancer cell line suppressed anchorage-independent growth and reduced tumor growth in a xenograft model. Hemizygous deletion promoted anchorage-independent growth, revealing that PKCβ is haploinsufficient for tumor suppression. Several mutations were dominant negative, suppressing global PKC signaling output, and bioinformatic analysis suggested that PKC mutations cooperate with co-occurring mutations in cancer drivers. These data establish that PKC isozymes generally function as tumor suppressors, indicating that therapies should focus on restoring, not inhibiting, PKC activity.
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•Cancer-associated PKC mutations are LOF and can act in a dominant-negative manner•Correcting a heterozygous PKCβ LOF mutation reduces tumor volume•Hemizygous deletion shows PKC is haploinsufficient for tumor suppression•Therapeutic strategies should aim to restore PKC activity instead of inhibiting it
Cancer-associated kinase mutations have generally been characterized as oncogenic, but an analysis of PKC mutations reveals that the majority are loss of function, indicating a tumor-suppressive role for this kinase and a shift in therapeutic strategies targeting PKC.
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