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BackgroundNeurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system.MethodsA5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA .10).ConclusionsThis is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

This paper examines the internationalisation processes in the higher education sector in Latvia and explores the motives of international students to study in Latvia, their experience and their plans. The study uses a quantitative data collection method -- a survey -- the results of which allow us to judge the main trends of internationalisation processes in Latvia. The differences between different groups were investigated, highlighting the countries with the most respondents -- India and Germany, and comparing them with each other and with students from other countries. The results show that there are substantial differences between the groups. For German students, Latvia was more of a second option when they failed to get into their preferred university in their home country or elsewhere. They chose to study in Latvia mainly because of the university's study programmes. At the same time, students from India were also interested in factors such as culture, the Baltic region and the attractiveness of Riga.

A study was conducted to examine the recombination processes in persistent phosphor Mg3Y2Ge3O12:Tb3+ garnet at low temperatures. Photoluminescence (PL), recombination luminescence (RL), electron paramagnetic resonance (EPR), and EPR detected by PL or RL were measured.In samples with low Tb3+ concentration, a broad PL and RL band around 400–450 nm and characteristic Tb3+ lines were observed. However, in samples with high Tb3+ concentration, only Tb3+ lines were present. Both the broad-band and the line components exhibit long-lasting tunneling luminescence with hyperbolic decay. After 263 nm UV irradiation signals of intrinsic electron (F-type) and hole (V-type) trapping centres were observed in the EPR spectra. Such signals were also observed in RL-detected EPR spectra, indicating that the broad RL band at low Tb3+ concentrations originates from tunneling recombination between these intrinsic traps. At high Tb3+ concentrations, the RL-EPR spectrum was not observed, suggesting that intrinsic electron and Tb-related hole trapping centres probably participate in the tunneling recombination.

Invariant natural killer T (iNKT) cells are a subset of lipid-reactive, unconventional T cells that have anti-tumor properties that make them a promising target for cancer immunotherapy. Recent studies have deciphered the developmental pathway of human MAIT and Vγ9Vδ2 γδ-T cells as well as murine iNKT cells, yet our understanding of human NKT cell development is limited. Here, we provide an update in our understanding of how NKT cells develop in the human body and how knowledge regarding their development could enhance human treatments by targeting these cells.

Drivers of global change are creating strongly contrasting early life conditions for developing offspring, which may have carry-over effects on lifetime fitness. We tested for “silver-spoon” effects of natal conditions (environmental conditions and maternal quality) and individual quality (pre-fledging) on the lifetime reproductive success (LRS) of aerial insectivorous adult tree swallows (Tachycineta bicolor) hatched in distinct populations with contrasting environments in Saskatchewan and British Columbia, Canada. In both populations, LRS of adults was influenced by environmental conditions they experienced as developing nestlings, but silver-spoon effects were context-dependent, indicating population-specific responses to the local environment. Higher natal temperature in Saskatchewan had positive silver-spoon effects on the LRS of adult swallows, but the opposite was observed in British Columbia, likely because the highest temperatures local recruits experienced as nestlings occurred during heat extremes. In Saskatchewan, where wetter conditions reflect higher wetland abundance and food supply, we detected a negative effect of good natal wetland conditions on adult LRS, contrary to our hypothesis. However, since current breeding wetland conditions are a strong driver of adult fitness, and adults experiencing high natal wetland abundance generally bred when wetland abundance was lower, we suspect any potential benefits of natal wetland abundance on LRS were overridden by wetland conditions during breeding. As hypothesized, wetter natal conditions in British Columbia, which reflect an unfavorable environment for developing nestlings, had negative silver-spoon effects on the LRS of adults. No maternal or pre-fledging quality effects were detected at either site. Therefore, LRS of individuals within distinct populations is influenced, at least in part, by carry-over effects of the natal environment that vary locally. Consequently, natal environmental conditions that affect fitness, with putative population-level consequences, may underly spatially-varying population trends of regionally distinct populations within a species’ range.

Precision optical measurements of the electron-spin precession of nitrogen-vacancy (NV) centers in diamond form the basis of numerous applications. The most sensitivity-demanding applications, such as femtotesla magnetometry, require the ability to measure changes in GHz spin transition frequencies at the sub-millihertz level, corresponding to a fractional resolution of better than 10^{−12}. Here we study the impact of microwave (MW) phase noise on the response of an NV sensor. Fluctuations of the phase of the MW waveform cause undesired rotations of the NV spin state. These fluctuations are imprinted in the optical readout signal and, left unmitigated, are indistinguishable from magnetic-field noise. We show that the phase noise of several common commercial MW generators results in an effective pTs^{1/2}-range noise floor that varies with the MW carrier frequency and the detection frequency of the pulse sequence. The data are described by a frequency-domain model incorporating the MW phase-noise spectrum and the filter-function response of the sensing protocol. For controlled injection of white and random-walk phase noise, the observed NV magnetic noise floor is described by simple analytic expressions that accurately capture the scaling with pulse sequence length and the number of π pulses. We outline several strategies to suppress the impact of MW phase noise and implement a version, based on gradiometry, that realizes a >10-fold suppression. Our study highlights an important challenge in the pursuit of sensitive diamond quantum sensors and is applicable to other qubit systems with a large transition frequency.

Background Acute inpatient mental health services report high levels of safety incidents. The application of patient safety theory has been sparse, particularly concerning interventions that proactively seek patient perspectives. Objective(s) Develop and evaluate a theoretically based, digital monitoring tool to collect real-time information from patients on acute adult mental health wards about their perceptions of ward safety. Design Theory-informed mixed-methods study. A prototype digital monitoring tool was developed from a co-design approach, implemented in hospital settings, and subjected to qualitative and quantitative evaluation. Setting and methods Phase 1: scoping review of the literature on patient involvement in safety interventions in acute mental health care; evidence scan of digital technology in mental health contexts; qualitative interviews with mental health patients and staff about perspectives on ward safety. This, alongside stakeholder engagement with advisory groups, service users and health professionals, informed the development processes. Most data collection was virtual. Phase 1 resulted in the technical development of a theoretically based digital monitoring tool that collected patient feedback for proactive safety monitoring. Phase 2: implementation of the tool in six adult acute mental health wards across two UK NHS trusts; evaluation via focused ethnography and qualitative interviews. Statistical analysis of WardSonar data and routine ward data involving construction of an hour-by-hour data set per ward, permitting detailed analysis of the use of the WardSonar tool. Participants A total of 8 patients and 13 mental health professionals participated in Phase 1 interviews; 33 staff and 34 patients participated in Phase 2 interviews. Interventions Patients could use a web application (the WardSonar tool) to record real-time perceptions of ward safety. Staff could access aggregated, anonymous data to inform timely interventions. Results Coronavirus disease 2019 restrictions greatly impacted the study. Stakeholder engagement permeated the project. Phase 1 delivered a theory-based, collaboratively designed digital tool for proactive patient safety monitoring. Phase 2 showed that the tool was user friendly and broadly acceptable to patients and staff. The aggregated safety data were infrequently used by staff. Feasibility depended on engaged staff and embedding use of the tool in ward routines. There is strong evidence that an incident leads to increased probability of further incidents within the next 4 hours. This puts a measure on the extent to which social/behavioural contagion persists. There is weak evidence to suggest that an incident leads to a greater use of the WardSonar tool in the following hour, but none to suggest that ward atmosphere predicts future incidents. Therefore, how often patients use the tool seems to send a stronger signal about potential incidents than patients’ real-time reports about ward atmosphere. Limitations Implementation was limited to two NHS trusts. Coronavirus disease 2019 impacted design processes including stakeholder engagement; implementation; and evaluation of the monitoring tool in routine clinical practice. Higher uptake could enhance validity of the results. Conclusions WardSonar has the potential to provide a valuable route for patients to communicate safety concerns. The WardSonar monitoring tool has a strong patient perspective and uses proactive real-time safety monitoring rather than traditional retrospective data review. Future work The WardSonar tool can be refined and tested further in a post Coronavirus disease 2019 context. Study registration This study is registered as ISRCTN14470430. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128070) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 14. See the NIHR Funding and Awards website for further award information. Plain language summary Mental health wards can feel unsafe. We know that patients and staff have different ideas about what makes a hospital ward safe or unsafe. Patients are often the first to know when the atmosphere on a ward becomes tense but, often, no one asks them for input or feedback at the time. We worked with service users and staff to develop new technology to make it easy for patients to tell staff about changes in the ward atmosphere. We put everyone’s ideas together and some technical developers then built a digital safety tool to use on a tablet computer. Patients put in anonymous information about the ward atmosphere and staff can read it straight away. We tested it on six adult acute mental health wards for 10 weeks. We asked patients and staff what they thought about the tool and we looked at how it was being used. Patients and staff liked the look of the tool on the tablet computer. Some staff said they did not need it because they could tell how patients were feeling, but patients told us that staff did not talk with them much and did not always know when patients were feeling tense. Coronavirus disease 2019 made life difficult on the wards. Most ward managers said the tool could be helpful, but they had not had time to get used to it on the wards. Occasionally, the tablet computers were out of action. Many staff tried hard to use the tool. Most patient information was gathered when it was calm, perhaps because staff were not too busy to help them. We found that this tool could help staff know about tensions on the ward, but they need to get used to it and bring it into ward routines. Scientific summary Context Mental health services report high levels of safety incidents. This is a concern and an NHS priority. UK government records for 2020–1 show 300,703 reported incidents in mental health services in England. Incidents in acute mental health wards frequently involve violence and self-harm. Safety incidents have been associated with increased costs and harm to patients and staff. Furthermore, one incident may increase the likelihood of further incidents, via a disturbed ward milieu and social contagion. Successfully avoiding one incident may therefore reduce the probability of future incidents. Patient perspectives on safety highlight factors such as not being listened to, or not feeling psychologically safe; however, incident reporting systems fail to capture the spectrum of patients’ safety concerns. Although patient involvement is a mental health research priority, patient-reported safety data are rarely collected. Onerous processes and fear of repercussions discourage experience experts from participating in mental health research. Patients may experience harm but have difficulties raising concerns with staff. If patients had opportunities to report safety issues in real time, staff could potentially respond and intervene before situations escalate. Interpersonal dynamics on acute mental health wards can change rapidly, affecting care quality and feelings of safety. Potentially, prospective clinical surveillance could promote safety by monitoring rather than simply measuring safety. Proactive day-to-day monitoring of patient perspectives might bring greater benefits than relying on retrospective review, and could be part of a broader vision to improve ward safety. Currently, there is no mechanism by which moment-to-moment safety data from patients on acute mental health wards can be captured and made available to staff in real time. Research aims This study’s focus was to use co-design to develop a digital tool for collecting and monitoring real-time data directly from patients on adult acute mental health wards, and to explore whether this information could be used by staff on a daily basis to anticipate and avoid developing incidents, thereby proactively managing safety. The objectives were: to co-design with service users and staff a digital innovation that will allow real-time monitoring of safety on acute mental health wards; to explore the feasibility and acceptability of capturing real-time feedback from service users about safety; to explore how staff use this information when reported during daily handovers (or other mechanism); to explore how the resulting data are related to quality and safety metrics; to explore how these data can be used longitudinally to promote safety. Methodology Two-phase, mixed-methods design. Literature reviews Scoping review of the literature on patient involvement in safety interventions Systematic searches of academic databases [Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, MEDLINE, EMBASE, Web of Science and Scopus] and grey literature (2000–20) were conducted March–June 2020. Additional sources included 14 mental health-specific sources (e.g. Centre for Global Mental Health); 25 non-mental health-specific sources (e.g. Royal College of Nursing); the National Institute for Health and Care Excellence (NICE) evidence database; ProQuest Thesis and Dissertations database and three social media platforms. Following screening, a narrative synthesis of included literature was conducted. A total of 52 studies were included; 33 focused on reducing staff use of restrictive practices. About half reported limited patient participation. Patients were involved mainly as co-thinkers, advisers and partners rather than decision-makers. Safety interventions ranged across organisational change, ward-level decision-making and individual interventions (e.g. mobile phone app). The more extensive their involvement, the more likely patients were to have active roles in the research. High patient involvement seemed to be focused on forensic mental health and associated with reduction in restrictive practices. Low patient involvement tended to be associated with less reduction in restrictive practices. However, methodological quality of the reviewed papers was inconsistent. Evidence scan of the application of digital technology in mental health contexts An evidence scan of the literature around digital technology in a mental health context was conducted in November 2020 (databases: CINAHL, PsycINFO and Web of Science). Research in this field appears largely focused on therapeutic interventions, such as assessment of suicidality, and psychological support therapies, such as counselling. Limited research on telecare and the design of mental health apps for other contexts was identified but digital technologies specifically for mental health care are relatively new. Many digital technologies for health (mainly apps) have been designed within the tech industry, not always using mental health expertise. There was an emphasis on usability and accessibility and there were some concerns around confidentiality. Provided digital technology does not cause patients any harm it is seen as potentially helpful and useful. Successful technology implementation is supported by a reliable internet connection, training for users of the technology, technical support, and effective communication and leadership. Theoretical basis The current study is aligned with patient safety theory, specifically the Measurement and Monitoring Safety Framework domain ‘sensitivity to operations’. This domain, which emphasises monitoring the safety of care as it is delivered in real time, recognises patients and families as important information sources; and highlights the need for staff to be responsive to subtle changes and disturbances. Contagion and milieu were taken as underpinning concepts for promoting ward safety and the development of the safety monitoring tool. A logic model for the WardSonar monitoring tool was developed with a supporting programme theory. Patient and public involvement and engagement A member of the core research team who is a lived experience expert led the approach to patient and public involvement and engagement. This was based around principles of equality, diversity and inclusion. Stakeholder engagement sessions advised on the development of the monitoring tool; critiqued monitoring tool prototypes; and informed the strategies for implementation and evaluation. Study design This was a two-phase mixed-methods design, supported by two NHS trusts. Phase 1: overlapping stages progressed towards conceptual clarification, followed by technical specification and delivery of a testable intervention. Key components were literature reviews, stakeholder interviews and meaningful stakeholder engagement. Technical developers produced a web app that used patient feedback via a tablet computer for proactive safety monitoring: the WardSonar safety monitoring tool. The patient interface employed a weather analogy with questions such as ‘How does the ward atmosphere feel to you today?’ (very calm to very stormy). The staff dashboard displayed aggregated and anonymised information collected via the patient interface in real time. Phase 2: the monitoring tool was implemented in two NHS trusts and evaluated via qualitative interviews, focused ethnography, pre- and post-intervention measures, real-time measures and routinely collected ward data. Two monitoring tools were given to each of the six participating adult acute mental health wards, including two psychiatric intensive care units. Staff were asked to use the tool to invite patients to record their perceptions of the ward atmosphere, three times daily. Changes to protocol The project commenced in the very early stages of the coronavirus disease 2019 (COVID-19) pandemic. Pragmatic adjustments produced a feasible alternative with some virtual Phase 1 data collection and discussions, adjusted timescales and the removal of a phase of small-scale testing. Modes of analysis and interpretation Qualitative evaluation Design Focused ethnographic observations on the six wards explored implementation context. Patient and staff perspectives were explored through individual interviews. Data were synthesised using a pen portrait analytical process. Findings The design of the tool was well received. There was variation between how it was perceived and implemented but general patterns emerged. Patients liked the opportunity to express their concerns and talk with staff who brought the tool to them, explaining that they believed staff were often unaware when patients felt unsafe. Most staff thought the tool prompted useful conversations and could be helpful, although psychiatric intensive care unit staff tended to say it was unnecessary. However, the tool’s functionality for informing safety interventions via aggregated patient data was poorly understood. There was a drop off in engagement with the tool over time. Ward managers discussed the difficulties of motivating busy and exhausted staff to embed the technology into ward routines. Quantitative evaluation Design Staff perceptions of safety culture and ward atmosphere were examined using a pre- and post-implementation design. Baseline measurements including the EssenCES© (Climate Evaluation Schema; Institute of Forensic Psychiatry and Sex Research, Essen, Germany) scale and the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture were taken at baseline and after a 10-week implementation period. Various statistical models were used to explore relationships between wards, WardSonar use and occurrence of incidents over time, including zero-inflated negative binomial models and ordinal logistic regression. The design matrix was consistent across all models. It consisted of fixed effects to capture time-invariant ward-specific effects, time of day variables and lagged values of incidents of WardSonar responses, depending on whether the model was explaining current incidents or current response. A simple linear trend determined any systematic deviation in use or response over time. Results Statistical analysis showed substantial and significant variation in the use of the device across wards, both in terms of the likelihood of any submission at a given time and the number of submissions. There were no statistically significant differences in staff perceptions of ward atmosphere or safety culture pre and post WardSonar implementation. Owing to the sample size, analyses were not conducted at the individual ward level. The volume of patient submissions via the monitoring tool corresponded more closely to incidents than ward atmosphere averages. It was lower over time, at night, at weekends, and when there were peaks in incidents. Submission volume decreased over time, but the probability of a submission reporting a better atmosphere increased slightly. Submission volume was higher during the daytime or before an incident and there was weak evidence of increased volume in the hour after an incident. The type of response for both direction and current atmosphere was not sensitive to whether or not there had been an incident. In terms of direction of atmosphere, there were significant differences across wards, but this was the only significant variable. Evenings led to greater likelihood of a worse atmosphere being reported, given that a submission was made. An incident in the previous four hours was strongly predictive of a further incident. An individual ‘stormy’ response or increased volume of submissions within the previous hour had some predictive value regarding a further incident. Qualitative analysis highlighted some data quality issues; for example, staff were more likely to collect submissions during quiet times and very unlikely to collect submissions during busy times; the tool was not used if the device was lost or otherwise out of action. There were some periods of days or weeks on some wards when no submissions were collected. The technology was pragmatically adapted for use within an NHS context. Some connectivity issues were identified, although data inputting did not seem to be affected. Further understanding of relationships between ward atmosphere and staff stress or absence due to sickness, contagion between incidents in the seclusion room and impact on staff and patients on the main ward and implementation processes would inform future implementation of WardSonar and interpretation of WardSonar data. Discussion The WardSonar patient safety monitoring tool can collect real-time data about patients’ perceptions of safety, to support staff in monitoring and improving the clinical environment. The research environment was affected by the COVID-19 pandemic and was severely atypical. Regarding the quantitative analysis, the lower volume of responses may have severely limited the power of the statistical analyses to identify statistically significant relationships between responses and outcomes. The decline in tool use over time may simply be an artefact of the pandemic or may have a number of causes. Previous studies have examined factors affecting participation and attrition in digital health technology research. The volume of routinely collected data was not affected and it is those data in which significant findings were identified. Strengths and limitations WardSonar’s strong patient perspective arguably gives it particular relevance for addressing patient safety. The co-design approach produced a tool that was apparently well designed, acceptable and easy to use. Stakeholder perspectives fundamentally impacted conceptualisation, development and operationalisation, adding to WardSonar’s validity. The separate components of the mixed-methods design were mutually beneficial, resulting in rounded insights into the study data, including strong evidence to support the idea of behavioural contagion between safety incidents. Some technical issues with connectivity cast doubt on the reliability of the tool. The amended research design was curtailed to adapt to the COVID-19 research context. The tools developed within the study used existing technology that was within budget and suitable for the research aims. Some technology challenges may be attributable to the limitations of this tool for data visualisation and could potentially be addressed in the future via a bespoke dashboard. Data were gathered from interviews with patients, staff and observations on each ward at selected time points, but because interviews were opportunistic, it is unclear how representative they were of staff and patient populations. Only the English language was used. It may have been valuable to include patients in the pre and post evaluation EssenCES (Climate Evaluation Schema) and Agency for Healthcare Research and Quality (AHRQ) assessments, although this could have been burdensome. Furthermore, one of the aims of assessing patient safety culture via the staff-facing AHRQ measure was to explore composite measures over time that linked to factors within the logic model and programme theory around how the staff dashboard may support staff in monitoring and improving the safety of the clinical environment. Equality, diversity and inclusion The current study was predicated on principles of equality, diversity and inclusion. Stakeholder perspectives were integral to design and development. The views of people not interviewed are unknown. Likewise, little information was collected concerning personal demographic characteristics of participants. This was a deliberate decision made with respect to the ethical arguments around collecting personal information, and because demographic information was not considered relevant in the current study. Reliance on the English language and the limited diversity data reduce the relevance of the results. Implications for decision-makers Further focus on the tool’s implementation in clinical practice warrants additional research; for example, implementation in a post COVID-19 environment could improve uptake, enhancing data validity. The WardSonar tool can facilitate measurement of contagion and may identify the likelihood of future incidents. The ability to monitor patient perspectives in real time provides a unique, proactive approach to safety. Avoiding reliance on the English language and collecting diversity data could broaden the relevance of the results in future studies. Future technical iterations could refine the staff dashboard and the model for deploying the tools in the ward environment. An approach whereby patients can input data unprompted may improve accuracy and reduce variation in use, enhancing results validity. Further development would require key decisions relating to ownership of the technology. Study registration This study is registered as ISRCTN14470430. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128070) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 14. See the NIHR Funding and Awards website for further award information.

BackgroundAcute mental health services report high levels of safety incidents that involve both patients and staff. The potential for patients to be involved in interventions to improve safety within a mental health setting is acknowledged, and there is a need for interventions that proactively seek the patient perspective of safety. Digital technologies may offer opportunities to address this need. ObjectiveThis research sought to design and develop a digital real-time monitoring tool (WardSonar) to collect and collate daily information from patients in acute mental health wards about their perceptions of safety. We present the design and development process and underpinning logic model and programme theory. MethodsThe first stage involved a synthesis of the findings from a systematic review and evidence scan, interviews with patients (n=8) and health professionals (n=17), and stakeholder engagement. Cycles of design activities and discussion followed with patients, staff, and stakeholder groups, to design and develop the prototype tool. ResultsWe drew on patient safety theory and the concepts of contagion and milieu. The data synthesis, design, and development process resulted in three prototype components of the digital monitoring tool (WardSonar): (1) a patient recording interface that asks patients to input their perceptions into a tablet computer, to assess how the ward feels and whether the direction is changing, that is, “getting worse” or “getting better”; (2) a staff dashboard and functionality to interrogate the data at different levels; and (3) a public-facing ward interface. The technology is available as open-source code. ConclusionsRecent patient safety policy and research priorities encourage innovative approaches to measuring and monitoring safety. We developed a digital real-time monitoring tool to collect information from patients in acute mental health wards about perceived safety, to support staff to respond and intervene to changes in the clinical environment more proactively.

Since the early 1990s, Latvia has experienced high levels of emigration. Still, current dynamics show that net migration has nearly ceased and that a growing share of new immigrant populations are from non-European countries. One of the leading causes of a sizable share of recent immigration is the globalisation of higher education and the mobility of international students. However, in recent decades, international student mobility (ISM) has brought attention to various aspects of higher education, educational export, and migration trends. This has captured the interest of academics and practitioners worldwide. Receiving countries recognise the importance of attracting international students as potential residents, especially as they undergo unfavourable demographic changes. The paper aims to present empirical evidence on ISM in Latvia by assessing international student daily life and study experiences. The focus is on examining the perspective of a host country. The study utilises statistical data, survey data and a case study of the University of Latvia to analyse the link between the origin of the student and their choosing Latvia as a non-traditional destination for quality higher education. The findings indicate that Latvia is an attractive destination for young migrants from diverse geographies, including Europe and Southeast Asia and consistent flows of students from former Soviet countries. One of the main factors that draw international students to Latvia is the affordability of education offered in English, providing a “second chance” for achieving success and specific clusters of degree students from European countries studying medicine.

Up to 3% of all hepatocellular carcinomas (HCCs) present with a tumor thrombus (TT) in the inferior vena cava (IVC) and right atrium (RA). Extensive growth of HCC into the IVC and the RA is associated with a particularly poor prognosis. This clinical condition is related to a high risk of sudden death due to pulmonary embolism or acute heart failure. Therefore, a technically challenging treatment undergoing hepatectomy and cavo-atrial thrombectomy is necessary. We report a 61-year-old man presenting with right subcostal pain, progressive weakness, and periodic shortness of breath for 3 months. He was diagnosed with advanced HCC with a TT extending from the right hepatic vein into the IVC and RA. A multidisciplinary meeting with cardiovascular and hepatobiliary surgeons, oncologists, cardiologists, anesthesiologists, and radiologists was held to determine the best treatment approach. Initially, the patient underwent right hemihepatectomy. As follows, the cardiovascular stage using cardiopulmonary bypass was successfully performed, removing the TT from the RA and ICV. In the early postoperative period, the patient remained stable and was discharged on the 8th postoperative day. A morphological examination revealed grade 2/3 HCC, a clear cell variant with microvascular and macrovascular invasion. Immunohistochemical staining was positive for HEP-1, CD10, whereas negative for S100. The morphological and immunohistochemical results corresponded to HCC. The treatment of such patients requires the cooperation of various specialties. Although the approach of the surgery is extremely complex including specific technical support, as well as high perioperative risks, the result offers favorable clinical outcomes.

BackgroundOf all the care provided in health care systems, major surgical interventions are the costliest and can carry significant risks. Enhanced Recovery After Surgery (ERAS) is a bundle of interventions that help improve patient outcomes and experience along their surgical journey. However, given that patients can be overwhelmed by the multiple tasks that they are expected to follow, a digital application, the ERAS app, was developed to help improve the implementation of ERAS. ObjectiveThe objective of this work was to conduct a thorough assessment of patient and provider experiences using the ERAS app. MethodsPatients undergoing colorectal or gynecological oncology surgery at 2 different hospitals in the province of Alberta, Canada, were invited to use the ERAS app and report on their experiences using it. Likewise, care providers were recruited to participate in this study to provide feedback on the performance of this app. Data were collected by an online survey and using qualitative interviews with participants. NVivo was used to analyze qualitative interview data, while quantitative data were analyzed using Excel and SPSS. ResultsOverall, patients found the app to be helpful in preparation for and recovery after surgery. Patients reported having access to reliable unbiased information regarding their surgery, and the app provided them with clarity of actions needed along their surgical journey and enhanced the self-management of their care. Clinicians found that the ERAS app was easy to navigate, was simple for older adults, and has the potential to decrease unnecessary visits and phone calls to care providers. Overall, this proof-of-concept study on the use of a digital health app to accompany patients during their health care journey has shown positive results. ConclusionsThis is an important finding considering the massive investment and interest in promoting digital health in health care systems around the world.

Purpose Hypertension should be confirmed with the use of home BP measurement (HBPM) or 24h ambulatory BP measurement (ABPM). The aim of our study was to compare measurements obtained by OBPM, HBPM and ABPM in individuals with elevated OBPM participating in the population-based Swiss Longitudinal Cohort Study (SWICOS). Material and Methods Participants with OBPM ≥140/90 mmHg assessed their BP using HBPM and ABPM. The cut-off for hypertension was ≥135/85 mmHg for HBPM, ≥130/80 mmHg for ABPM. White-coat hypertension (WCH) was defined as normal HPBM and ABPM in participants not taking antihypertensive drugs. Uncontrolled hypertension was defined as hypertension in HBPM or ABPM despite antihypertensive treatment. Results Of 72 hypertensive subjects with office BP ≥140/90 mmHg and valid measurements of HBPM and ABPM, 39 were males (aged 62.8 ± 11.8y), 33 were females (aged 57.4 ± 14.2y). Hypertension was confirmed with HBPM and ABPM in 17 participants (24%), with ABPM only in 24 further participants (33%), and with HBPM only in 2 further participants (3%). Participants who had hypertension according to ABPM but not HBPM were younger (59 ± 11 y versus 67 ± 16 y; p

BackgroundCardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH.MethodsWe constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit.ResultsAmong 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P = .003; lower by 2.17 [SD, 0.67] in women, P = .001; lower by 0.78 [SD, 0.32] in men, P = .016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women.ConclusionsBaseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time.

Representatives of the bacterial genus Aeromonas are some of the most notorious aquaculture pathogens associated with a range of diseases in different fish species. As the world forges toward the post-antibiotic era, alternative options for combating bacterial pathogens are needed. One such alternative option is phage biocontrol. In this study, a novel podophage—JELG-KS1—infecting Aeromonas salmonicida was retrieved from wastewater along with its host strain. The genome of the JELG-KS1 phage is a 40,505 bp dsDNA molecule with a GC% of 53.42% and 185 bp direct terminal repeats and encodes 53 predicted proteins. Genomic analysis indicates that JELG-KS1 might represent a novel genus within the subfamily Studiervirinae. Podophage JELG-KS1 is a strictly lytic phage without any identifiable virulence or AMR genes that quickly adsorbs onto the surface of host cells to initiate a 48 min long infectious cycle, resulting in the release of 71 ± 12 JELG-KS1 progeny virions per infected cell. JELG-KS1 effectively lyses its host population in vitro, even at very low multiplicities of infection. However, when challenged against a panel of Aeromonas spp. strains associated with diseases in aquaculture, JELG-KS1 shows host-specificity that is confined only to its isolation strain, immediately compromising its potential for Aeromonas spp. biocontrol in aquaculture.

Background Mental health crises cause significant disruption to individuals and families and can be life-threatening. The large number of community crisis services operating in an inter-agency landscape complicates access to help. It is unclear which underpinning mechanisms of crisis care work, for whom and in which circumstances. Aim The aim was to identify mechanisms to explain how, for whom and in what circumstances adult community crisis services work. Objectives The objectives were to develop, test and synthesise programme theories via (1) stakeholder expertise and current evidence; (2) a context, intervention, mechanism and outcome framework; (3) consultation with experts; (4) development of pen portraits; (5) synthesis and refinement of programme theories, including mid-range theory; and (6) identification and dissemination of mechanisms needed to trigger desired context-specific crisis outcomes. Design This study is a realist evidence synthesis, comprising (1) identification of initial programme theories; (2) prioritisation, testing and refinement of programme theories; (3) focused realist reviews of prioritised initial programme theories; and (4) synthesis to mid-range theory. Main outcome The main outcome was to explain context, mechanisms and outcomes in adult community mental health crisis care. Data sources Data were sourced via academic and grey literature searches, expert stakeholder group consultations and 20 individual realist interviews with experts. Review methods A realist evidence synthesis with primary data was conducted to test and refine three initial programme theories: (1) urgent and accessible crisis care, (2) compassionate and therapeutic crisis care and (3) inter-agency working. Results Community crisis services operate best within an inter-agency system. This requires compassionate leadership and shared values that enable staff to be supported; retain their compassion; and, in turn, facilitate compassionate interventions for people in crisis. The complex interface between agencies is best managed through greater clarity at the boundaries of services, making referral and transition seamless and timely. This would facilitate ease of access and guaranteed responses that are trusted by the communities they serve. Strengths and limitations Strengths include the identification of mechanisms for effective inter-agency community crisis care and meaningful stakeholder consultation that grounded the theories in real-life experience. Limitations include the evidence being heavily weighted towards England and the review scope excluding full analysis of ethnic and cultural diversity. Conclusions Multiple interpretations of crises and diverse population needs present challenges for improving the complex pathways to help in a crisis. Inter-agency working requires clear policy guidance with local commissioning. Seamless transitions between services generate trust through guaranteed responses and ease of navigation. This is best achieved where there is inter-agency affiliation that supports co-production. Compassionate leaders engender staff trust, and outcomes for people in crisis improve when staff are supported to retain their compassion. Future work Further work might explore inter-agency models of crisis delivery, particularly in rural communities. Future work could focus on evaluating outcomes across crisis care provider agencies and include evaluation of individual, as well as service-level, outcomes. The implementation and effect of mental health triage could be explored further, including via telehealth. Barriers to access for marginalised populations warrant a specific focus in future research. Study registration The study is registered as PROSPERO CRD42019141680. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 15. See the NIHR Journals Library website for further project information. Plain language summary The issue A mental health crisis can be traumatic for individuals and families. There are a lot of different agencies delivering crisis care. This can make getting the right help from services difficult, confusing and slow. It is not clear which services work best or who they work best for. What we did This research explored community mental health crisis services for adults. We focused on what is working, who it is working for and in what situations it is working. Service users, carers, mental health professionals and service managers formed an ‘expert stakeholder group’ to guide the project by helping the researchers make sense of what we learned. We gathered information from research reports, other documents and interviews with experts (i.e. service users, carers, professionals, managers). We focused on three questions: How can services make sure that people in crisis can get the right help, quickly? What makes crisis care compassionate? Does it help if different crisis services work together? What we learned Community crisis services are most compassionate and effective when staff from different organisations share information. When leaders of crisis care help staff to work together across services, they find better ways to help people. Close working across teams gives professionals a better understanding of what other services do and makes it easier for them to give people the right help at the right time. When leaders are kind and supportive to staff, they feel better at work and provide better crisis care. What future work can be done It would be useful to explore if the most effective crisis services are the same ones that service users like best. We need to know more about mental health triage, inter-agency working and telehealth. Our project did not explore diversity, but this is an important topic to investigate. Scientific summary Background Mental health crises cause significant disruption to the lives of individuals and families and can be life-threatening. The drive for community care alongside large reductions in hospital beds has led to a proliferation of community crisis services delivered by a diverse range of provider agencies, contributing to difficulties for people in navigating to timely crisis support. There is no single definition of a mental health crisis; people have diverse needs, resulting in a large variation in routes into and through mental health crisis care. Service users report unmet need. Services have diversified quickly in response to reported gaps and delayed responses, and continue to do so. Diversification has led to geographic differences in available crisis care and created a complex web of agencies with different values, referral processes, interventions and access thresholds. It is unclear, in this complex system, which underpinning mechanisms of crisis care are most effective, for whom and in which circumstances. Aim The aim was to identify mechanisms to explain how, for whom and in what circumstances mental health community crisis services for adults work to resolve crises, with a view to informing current and future intervention design and development. Objectives Use stakeholder expertise, current practice and research evidence to develop programme theories to explain how different crisis services work to produce the outcome of resolution of mental health crises. Use a context, intervention, mechanism and outcome (CIMO) framework to construct a sampling frame to identify subsets of literature within which to test programme theories. Iteratively consult, via an expert stakeholder group (ESG) and individual interviews, with diverse stakeholders to test and refine programme theories. Identify and describe pen portraits of UK crisis services that provide exemplars of the programme theories to explain how mental health crisis interventions work in order to explore and explain contextual variation. Synthesise, test and refine the programme theories, and, where possible, identify mid-range theory, to explain how crisis services work to produce the outcome of resolution of the crisis. Provide a framework for future empirical testing of theories in and for further intervention design and development. Produce dissemination materials that communicate the most important mechanisms needed to trigger desired context-specific crisis care outcomes, to inform current and future crisis care interventions and service designs. Design A four-phase realist evidence synthesis, reported in accordance with Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) reporting guidelines and comprising (1) identification of candidate programme theories from academic and grey literature; (2) iterative consultation with an ESG and individual interviews to prioritise, test and refine programme theories; (3) focused realist reviews of prioritised theory components; and (4) synthesis to mid-range theory. Main outcome measures The principal aim of the review was to generate and test programme theories, and then synthesise these with mid-range theory, to explain what works, for whom and in what circumstances in adult mental health community crisis care. Data sources The following were conducted: Google Scholar (Google Inc., Mountain View, CA, USA) searches to identify initial programme theories and logic models, focused searches of academic databases with backward citation searching, grey literature searches and hand-searches by the research team and expert stakeholders to test and refine three theory components. An ESG, with membership from lived experience, health professional, social care, policy expertise, health management and commissioning, was consulted on four occasions across the life of the research to test and refine theories and to connect them with real-world experience. Twenty individual realist interviews were conducted with 19 participants to further test, refine and sense-check theory components where there were gaps in topic expertise or theory; the 19 participants included service users; health, social care, ambulance and police professionals; and research and policy experts. Analysis A realist evidence synthesis with stakeholder primary data was used to test and refine three initial programme theories in adult mental health community crisis care: (1) urgent and accessible crisis care, (2) compassionate and therapeutic crisis care and (3) inter-agency working. Data analysis involved using realist logic to identify initial programme theories (objectives 1–3), and testing and refining the programme theories through a focused review of the literature, to extract and configure explanatory causal relationships between CIMO (objectives 3–5). Expert stakeholder consultations supported analysis through linking theories to real-world experience, enabling exploration and explanation of contextual variation as it related to putative mechanisms (objectives 3–5). Individual interviews with experts, who were purposively selected for their topic expertise related to the programme theory components, were deductively analysed according to the CIMO framework. An inductive process identified any new mechanisms not identified from other data sources (objective 3). Pen portraits were developed as illustrative exemplars of the link between CIMO and were refined in collaboration with expert stakeholders (objective 4). Findings from the focused review of the three theory components were synthesised with mid-range theories to produce a framework for any future empirical testing that may be developed (objective 5). Results The scope of the realist review was refined through an initial consultation and discussion between the ESG and the research team. A Diamond-9 prioritisation process was used to facilitate discussion between the ESG and the research team and to refine the scope of the review. This process resulted in three initial programme theories for testing, focused on (1) urgent and accessible crisis care, (2) compassionate and therapeutic crisis care and (3) inter-agency working. The findings from the three focused reviews were synthesised with mid-range theory. Mental health crisis care is provided by a complex array of agencies, each with different definitions of crises, different values about the nature of interventions and different approaches to prioritisation. This is further complicated by multiple overlapping service boundaries. What is apparent is that these differences can only be accommodated within an inter-agency system in which information and decisions are shared from commissioning through to front-line delivery. Inter-agency working provides mechanisms that trigger seamless service delivery through improved communication and collaboration. For this system to work, representation from all agencies and stakeholders is needed. National co-ordination at policy level ensures that investment is appropriately targeted and that important strategic aspirations are met. National co-ordination should steer, but not dictate, local configurations of the agencies needed. Local crisis services should be configured to meet the crisis care needs of local populations within their geography, taking account of any marginalised individuals or communities they serve. Commissioning for inter-agency working needs a focus on managing complex boundaries and transitions across agencies to avoid gaps and disputes. Attention is also needed on how the inter-agency crisis system engages with wider systems important to resolution of crises, including, for example housing, police, local authority, safeguarding and the justice system. The ultimate aim of inter-agency system should be that there is no wrong door through which to access mental health crisis care, and, once in a service, navigation should be facilitated via a single trusted point of liaison. Evaluation is not restricted by organisational boundaries and aims to provide data that take account of how the whole inter-agency system is operating. Conceptualisations of crises as single events or as the sole responsibility of statutory secondary mental health systems are unhelpful and generate fragmentation, leading to gaps and delays for those seeking crisis care and frustration for leaders and front-line staff. The perception of whether or not a service and service providers are accessible carries more of an inhibitive effect than the way that the service is actually organised. People experiencing a crisis choose to access services they perceive as providing a guaranteed response, that are easy to navigate to and that fit with their definition of the crisis. Although the timing of responses in relation to outcomes remains unclear, what is clear is that people feel safer and have a reduced sense of urgency when they trust services. Trust is established through compassionate interactions and proactive management of transitions and waiting. Involvement of the person and their family or support network in decisions supports a sense of trust and relational safety, which may help meet a need for continuity for some. To sustain compassion, front-line staff need access to support for themselves, as well as resources to deliver crisis care that meets their personal and professional ideals. Training in the knowledge, skills and values required for compassion can build confidence among front-line staff in all agencies. System leaders must provide resources and communicate an expectation for compassionate engagement so that it becomes the norm for staff to seek support. This is achieved in an inter-agency context when there is interpersonal contact between all levels of worker, from commissioning through to front-line delivery, that facilitates learning, communication and appreciation of different roles. Furthermore, co-production of crisis care can be facilitated within the inter-agency system, enabling crisis care to be recognised and valued by the community it serves. Service users perceive a crisis when they feel overwhelmed and anxious and when they perceive that they lack a sense of control. Familiar contacts and a safe environment, coupled with reassurance, can help to shape their perception of the service, but, more importantly, can help to reduce distress, thereby mitigating risk and making it more likely that a service user is able to respond to suggested strategies. With an emphasis on rapport and compassion, professionals are encouraged to exhibit positive behaviours that mitigate against the dehumanisation and stigma that service users may perceive when they encounter a service, and which may precipitate or exacerbate a crisis. Compassion shown to front-line staff by leaders leads to compassionate care. A tension between exerting control and providing support was evident at all levels. As integrated care systems are introduced, there is an aspiration that strategic partnerships will reduce competing priorities, which appear debilitating to organisations. Alongside these strategic partnerships, there is a need for coherent local strategies for compassionate and psychologically safe crisis care cognisant of the fact that high-quality care can coexist alongside the worst examples of care in the same organisation. Strategies should include how compassionate and psychologically safe crisis care is provided. Different values and definitions of crisis are accommodated, allowing challenge and debate to become accepted as an opportunity to drive quality improvement. Strengths and limitations Much of the literature was descriptive; therefore, the evidence base was limited. The programme theories identified outline the mechanisms needed to facilitate the best inter-agency community crisis care. Meaningful consultation with expert stakeholders grounded the theories in the reality of community crisis care, although UK evidence is heavily weighted towards England. Project delivery was affected by the COVID-19 pandemic, reducing the number of individual interviews and delaying stakeholder consultations. Stakeholder consultation did not reach as wide a group as originally intended. Conclusion Community crisis care is likely to continue to be delivered by a complex array of agencies responding to a heterogeneous population that presents with different mental health concerns and perceptions of crisis. Inter-agency working provides a platform for seamless transitions between services and timely responses. To deliver desired outcomes, inter-agency working requires continual systems of engagement locally and nationally involving all providers of crisis care through compassionate leadership, sharing of values and shared understanding of systems. Compassion is central and begins with leaders who can influence the culture of crisis organisations. Compassionate leadership is focused on people over systems, enabling front-line staff to retain their compassion and hope, and to work collaboratively across agencies, and it provides a platform for shared decision-making and co-production. All of this helps people in crisis to recognise the service as designed for them and to have trust in community crisis services. The study achieved its objectives, despite unexpected difficulties resulting from the effects of the COVID-19 pandemic, owing to an agile and committed research team, flexible and accommodating stakeholders and support from the funders. Project milestones were adjusted to accommodate the changing context of the study. Future work A framework of programme theories synthesised with mid-range theory developed from this study can inform future research that seeks to develop better mental health crisis care systems. Further work might explore how inter-agency service configurations work, including how telehealth interventions are perceived by service users and how these interventions produce optimal outcomes. Evaluation of crisis care for marginalised groups is needed. The implementation and effect of mental health triage could be explored further. Meaningful engagement with expert stakeholders could be incorporated routinely into research design and delivery. Mental health triage appears to be a promising approach, but has a limited evidence base. Future research could explore and test the implementation and effect of mental health triage systems. This work could focus on different values about prioritisation and how these can be accommodated within an inter-agency system. Further exploration of models of crisis care to mitigate barriers to access for those with substance use or alcohol use problems, personality disorders, physical health conditions and autistic spectrum disorders is needed. Inter-agency models of crisis care are causally linked to optimal crisis outcomes. A focused realist evaluation is needed to explore in more depth the factors influencing access to, and transition through, crisis care for these populations. These outcomes are at times theoretical and have been subjected to limited testing in primary research. UK inter-agency crisis service models provide an opportunity for mixed-method case study approaches to evaluation. A neglected area of focus for this research is the efficacy of models for rural populations. Crisis interventions involving police and mental health services have a growing body of evidence; however, there is a lack of evidence for co-response models involving ambulance paramedic staff or emergency control rooms. There is a lack of focus on individual recovery outcomes. This review highlights the importance of mechanisms such as psychological and relational safety, compassion and trust in producing optimal crisis outcomes. Research is needed to develop evaluation approaches to measure the presence and impact of these mechanisms in crisis care. Data from the literature and from engagement with stakeholders (via the ESG and individual interviews) were combined to refine the realist programme theory/ies to identify key mechanisms that might operate across multiple interventions to ‘trigger’ an appropriate treatment response, and contexts related to these key mechanisms that might enhance or detract from intervention success. Meaningful co-production with service users and other expert stakeholders enhances the relevance of research and should be incorporated routinely into research design and delivery. Study registration The study is registered as PROSPERO CRD42019141680. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR127709) and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 15. See the NIHR Journals Library website for further project information.

The present study evaluates the mold fungal resistance of newly developed loose-fill thermal insulation materials made of wheat straw, corn stalk and water reed. Three distinct techniques for the processing of raw materials were used: mechanical crushing (Raw, ≤20 mm), thermo-mechanical pulping (TMP) with 4% NaOH and steam explosion pulping (SEP). An admixture of boric acid (8%) and tetraborate (7%) was applied to all processed substrates due to their anti-fungal properties. The fourth sample group was prepared from SEP substrates without added fungicide (SEP*) as control. Samples from all treatments were separately inoculated by five different fungal species and incubated in darkness for 28 days at 28 °C and RH > 90%. The highest resistance to the colonization of mold fungi was achieved by TMP and SEP processing, coupled with the addition of boric acid and tetraborate, where molds infested only around 35% to 40% of the inoculated sample area. The lowest mold fungi resistance was detected for the Raw and SEP* samples, each ~75%; they were affected by rich amount of accessible nutrients, suggesting that boric acid and tetraborate additives alone did not prevent mold fungal growth as effectively as in combination with TMP and SEP treatments. Together, the achieved fungal colonization scores after combined fungicide and pulping treatments are very promising for the application of tested renewable materials in the future development of thermal insulation products.

Birch outer bark extract (BBE), containing pentacyclic triterpenes such as betulin, lupeol, and betulinic acid, is a widely recognized natural product renowned for its diverse pharmacological effects. However, its limited water solubility restricts its bioavailability. Therefore, the main objective is to enhance the bioavailability of BBE for pharmaceutical use. In this study, we aimed to develop a dispersion system utilizing a unique oleogel-producing method through the recrystallization of BBE from an ethanol solution in the oil phase. We generated an oleogel that demonstrates a notable 42–80-fold improvement in betulin and lupeol peroral bioavailability from BBE in Wistar rats, respectively. A physical paste-like BBE hydrogel developed with antisolvent precipitation showed a 16–56-fold increase in the bioavailability of betulin and lupeol from BBE in rat blood plasma, respectively. We also observed that the repeated administration of the BBE oleogel did not exhibit any toxicity at the tested dose (38.5 mg/kg betulin, 5.2 mg/kg lupeol, 1.5 mg/kg betulinic acid daily for 7 days). Betulin and betulinic acid were not detected in rat heart, liver, kidney, or brain tissues after the peroral administration of the oleogel daily for 7 days. Lupeol was found in rat heart, liver, and kidney tissues.