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Abstract Background Despite current best practices, pressure injuries (PI) remain a devastating and prevalent hospital-acquired complication for patients with acute traumatic spinal cord injuries (SCIs). This study examined associations between risk factors for PI development in patients with complete SCI, such as norepinephrine dose and duration, and other demographic factors or lesion characteristics. Methods This case–control study included adults with acute complete SCIs ASIA-A, who were admitted to a level-one trauma center between 2014–18. A retrospective review was implement using data on patient and injury characteristics, including age, gender, level of SCI (cervical vs. thoracic), Injury Severity Score (ISS), length of stay (LOS) and mortality; presence/absence of PI during their acute hospital stay; and treatment factors such as spinal surgery, mean arterial pressure (MAP) targets, and vasopressor treatment. Multivariable logistic regression evaluated associations with PI. Results Eighty-two out of 103 eligible patients had complete data, and 30 (37%) developed PIs. Patient and injury characteristics, including age (Mean: 50.6; SD:21.3), location of SCI (48 cervical, 59%) and ISS (Mean 33.1; SD:11.8), did not differ between PI and non-PI groups. Logistic regression analysis revealed that male gender (OR:34.1; CI95:2.3–506.5, p = 0.010) and increased LOS (log-transformed; OR:20.5, CI95:2.8–149.9, p = 0.003) were associated with increased risk of PI. Having an order for a MAP > 80mmg (OR:0.05; CI95:0.01–0.30, p = 0.001) was associated with a reduced risk of PI. There were no significant associations between PI and duration of norepinephrine treatment. Conclusions Norepinephrine treatment parameters were not associated with development of PI, suggesting that MAP targets should be a focus for future investigations for SCI management. Increasing LOS should highlight the need for high-risk PI prevention and vigilance.

Background and aims – Keraunea is a Brazilian endemic genus that has sat uncomfortably in Convolvulaceae where it was placed due to an enlarged and adnate fruit bract typical of Neuropeltis. A recent molecular phylogeny suggested that two of its five morphologically almost identical species actually belong to two different families, Malpighiaceae (superrosids) and Ehretiaceae (superasterids). Later studies have demonstrated that Keraunea effectively belongs to Ehretiaceae, but the proposal of one species belonging to Malpighiaceae has remained problematic. In this study, we re-assess this hypothesis, discuss the issues that have led to this assumption, and offer insights on the importance of carefully using herbarium collections and incorporating morphological evidence in systematic studies. Material and methods – Sequences of matK, rbcL, and ITS for all 77 currently accepted genera of Malpighiaceae, K. brasiliensis and Elatinaceae (outgroup) were compiled from GenBank and analysed with Maximum Likelihood and Bayesian Inference criteria for nuclear, plastid and combined datasets. Additional database and herbarium studies were performed to locate and analyse all duplicates of the holotype of K. brasiliensis to check for misidentified or contaminated material. Key results – Our examination of expanded DNA datasets and herbarium sheets of all K. brasiliensis isotypes revealed that a mistake in tissue sampling was, in fact, what led to this species being proposed to belong in Malpighiaceae. Kew’s isotype had a leaf of Malpighiaceae (likely Mascagnia cordifolia) stored in the fragment capsule, which was sampled and sequenced instead of the actual leaves of K. brasiliensis. Recently published studies have settled the placement of Keraunea in Ehretiaceae (Boraginales) and proposed three additional species. Conclusions – DNA sequences can be helpful in classifying taxa when morphology is conflicting or of a doubtful interpretation, with molecular phylogenetic placement being established as a popular tool accelerating the discovery of systematic relationships. Nonetheless, molecular techniques are also susceptible to methodological mistakes, which necessitates building a solid foundation of plant morphology and taxonomy to avoid artefacts in phylogenetic studies.

Abstract Background Infections are one of the leading causes of death in the neonatal period. This trial aims to evaluate if the provision of alcohol-based hand rub (ABHR) to pregnant women for postnatal household use prevents severe infections (including sepsis, diarrhoea, pneumonia, or death) among infants during the first three postnatal months. Methods Through a cluster-randomised trial in eastern Uganda, 72 clusters are randomised in a 2-arm design with rural villages as units of randomisation. We estimate to include a total of 5932 pregnant women at 34 weeks of gestation. All women and infants in the study are receiving standard antenatal and postnatal care. Women in the intervention group additionally receive six litres of ABHR and training on its use. Research midwives conduct follow-up visits at participants’ homes on days 1, 7, 28, 42, and 90 after birth and telephone calls on days 14, 48, and 60 to assess the mother and infant for study outcomes. Primary analyses will be by intention to treat. Discussion This study will provide evidence on the effectiveness of a locally available and low-cost intervention in preventing neonatal sepsis and early infant infections. If ABHR is found effective, it could be implemented by adding it to birthing kits. Trial registration Pan African Clinical Trial Registry, PACTR202004705649428. Registered 1 April 2020, https://pactr.samrc.ac.za/ .

IntroductionHead and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, which are mostly benign in nature. Amongst all genes, Succinate Dehydrogenase Subunit D (SDHD) is the most commonly mutated in familial HNPGLs. In about 30% of HNPGLs, germline mutations in SDHD can also occur in the absence of positive family history, thus giving rise to “occult familial” cases. Our aim was to evaluate the pattern of SDHD germline mutations in Czech patients with HNPGLs.Materials and methodsWe analyzed a total of 105 patients with HNPGLs from the Otorhinolaryngology departments of 2 tertiary centers between 2006 – 2021. All underwent complex diagnostic work-up and were also consented for genetic analysis.ResultsEighty patients aged 13-76 years were included; around 60% with multiple PGLs were males. Carotid body tumor was the most frequently diagnosed tumor. Germline SDHD mutation was found in only 12% of the Czech patients; approximately 78% of those harboring the mutation had negative family history. The mutation traits had higher affiliation for multiple tumors with nearly 70% patients of ≤ 40 years of age.ConclusionAn SDHD mutation variant was shared amongst unrelated patients but no founder-effect was established. Our findings confirmed that the pattern of SDHD mutation distribution amongst HNPGLs in Czech Republic differs from most studies worldwide.

The article presents the potential of freight railway transport in terms of saving of emissions and maximizing the efficiency of operation. Attention is paid to the transport of freight trains on electrified lines with higher gradients (up to 25‰), alternatively with the possibility of a trip to non-electrified lines and sidings, which generate significant extra costs in the operation of trains and are often a reason for the carrier to deploy a locomotive of independent traction (diesel-electric) even in electrified line sections, even at the cost of increased operating costs and increased emissions. There are many such lines and possibilities of use within the Central European region and the Czech Republic. In the first part of the article, the basic categorisation of dual-mode freight locomotives and their suitability for individual operating programmes is presented. This part also describes current situation on the rolling stock market in general and directions of development taken by various locomotive manufacturers. Case studies of deployment of real freight locomotives on chosen Czech railway lines are used in the next part to present the possibilities for energy and cost savings when replacing a vehicle with independent traction by an electric or dual-mode locomotive, at least in sections equipped with overhead catenary. The pros and cons of using several possible solutions are described in detail. Further considerable savings can be achieved by, among other things, using regenerative braking and returning the generated electricity back to the catenary system when driving downhill. In this respect, however, it is also necessary to cooperate with the infrastructure manager, who must also adapt the railway lines to the operation of these vehicles. Finally, general rules for operational deployments on which the replacement of a conventional vehicle by a dual or pure electric vehicle can be considered are formulated.

Bartonelloses are neglected emerging infectious diseases caused by facultatively intracellular bacteria transmitted between vertebrate hosts by various arthropod vectors. The highest diversity of Bartonella species has been identified in rodents. Within this study we focused on the edible dormouse (Glis glis), a rodent with unique life-history traits that often enters households and whose possible role in the epidemiology of Bartonella infections had been previously unknown. We identified and cultivated two distinct Bartonella sub(species) significantly diverging from previously described species, which were characterized using growth characteristics, biochemical tests, and various molecular techniques including also proteomics. Two novel (sub)species were described: Bartonella grahamii subsp. shimonis subsp. nov. and Bartonella gliris sp. nov. We sequenced two individual strains per each described (sub)species. During exploratory genomic analyses comparing two genotypes ultimately belonging to the same species, both factually and most importantly even spatiotemporally, we noticed unexpectedly significant structural variation between them. We found that most of the detected structural variants could be explained either by prophage excision or integration. Based on a detailed study of one such event, we argue that prophage deletion represents the most probable explanation of the observed phenomena. Moreover, in one strain of Bartonella grahamii subsp. shimonis subsp. nov. we identified a deletion related to Bartonella Adhesin A, a major pathogenicity factor that modulates bacteria-host interactions. Altogether, our results suggest that even a limited number of passages induced sufficient selective pressure to promote significant changes at the level of the genome.

Rocket (Eruca vesicaria subsp. sativa) is a source of sulfur-containing glucosinolates (GSLs). GSLs and their breakdown hydrolysis products (GHPs) are responsible for health-related benefits, such as anti-cancer and anti-neurodegenerative properties. Understanding how phytochemical composition changes between cultivation environments is key to developing cultivars with improved nutritional quality. Two consecutive harvests (first and second regrowth) of crops, grown in both Italy and the UK, were used to determine the phytochemical and transcriptomic differences between six lines of Eruca. Samples were taken upon delivery from field sites (D0) and after five days of cold storage (D5) for each location. Leaves were analysed for sulfur content, volatile organic compounds (VOCs), GSLs, GHPs, and sugars. Transcriptome data were associated with metabolite profiles to identify differentially expressed genes between plants grown in the two environments. VOC compounds (carbon disulfide, methyl thiocyanate) were associated with growth environment and with differences in sulfur metabolism gene expression (APR2, LSU2, LSU3, SDI1, SiR), GSL biosynthesis (MYB28, FMOGS-OX2) and GHP formation (ESM1, TGG1, TGG2). The concentrations of sugars were an order of magnitude greater in UK grown samples (up to 29.9 mg g-1 dry weight; dw). Sulfur content was significantly higher in the Italy plant samples (11.4 – 20.1 mg g-1 dw), which was in turn associated with higher concentrations of GSLs (pentyl GSL, up to 15.8 μmol g-1 dw; sinigrin, up to 0.005 μmol g-1 dw; glucoraphanin, up to 5.1 μmol g-1 dw; glucorucolamine, up to 23.6 μmol g-1 dw; neoglucobrassicin, up to 5.3 μmol g-1 dw) and hydrolysis products (sativin, up to 13.5 μmol g-1 dw; erucin, up to 1 μmol g-1 dw; sulforaphane, up to 34.7 μmol g-1 dw). VOC profiles of plants cultivated in the UK were distinct from Italy grown plants, with higher relative abundances of alkanes and esters in second cut and shelf-life (D5) samples. The data indicate a significant interaction of cultivar response with environment, highlighting the difficulty of producing Eruca crops with consistent phytochemical and postharvest traits. Genes with differential expression between plants grown in Italy and the UK could be used as markers of phytochemical quality and composition.

ABSTRAK Berdasarkan penelitian dengan judul “Electrical and Mechanical Properties of Fly Ash Filled Silicone Rubber for High Voltage Insulator†oleh Manjang dkk., (2015), telah dilakukan eksperimen uji karakteristik dielektrika fly ash sebagai filler pada isolator Silicone Rubber (SiR), namun belum adanya analisa optimasi komposisi kadar fly ash yang dilakukan, sehingga belum diperoleh nilai rekomendasi komposisi terbaik. Oleh karena itu, tujuan pada penelitian ini dilakukan studi lebih lanjut untuk menentukan nilai optimasi dari jenis komposisi pemanfaatan fly ash sebagai filler pada isolator SiR dengan metode analisa regresi kuadratik dan memperoleh model kuadrat komposisi fly as yang mengoptimalkan kekuatan dielektrika. Hasil optimasi komposisi fly ash pada pengujian sifat hidrofobik sebesar 20.69% dari komposisi fly ash dan pengujian permitivitas relatif sebesar 80% dari komposisi fly ash. Kata kunci: fly ash batu bara, filler, optimasi, regresi kuadratik, silicone rubber  ABSTRACT Based on research entitled "Electrical and Mechanical Properties of Fly Ash Filled Silicone Rubber for High Voltage Insulators" by Manjang et al., (2015), experiments have been carried out to test the dielectric characteristics of fly ash as a filler on Silicone Rubber (SiR) insulators, but there is no the optimization analysis of the composition of the fly ash content was carried out, so that the best composition recommendation value has not been obtained. Therefore, the aim of this research is to conduct further studies to determine the optimization value of the type of composition utilizing fly ash as filler in SiR insulators using the quadratic regression analysis method and obtain a quadratic model of fly ash composition that optimizes dielectric strength. Optimization results of the fly ash composition in testing the hydrophobic properties of 20.69% of the fly ash composition and relative permittivity testing of 80% of the fly ash composition. Keywords: coal fly ash, filler, optimization, quadratic regression, silicone rubber

Introduction Predictors of neurodevelopment among children who are HIV‐exposed uninfected (CHEU) are poorly understood. Methods Mothers with and without HIV and their children were enrolled during 6‐week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1‐year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site. Results At 1‐year evaluation, CHEU (n = 709) and children who are HIV‐unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate‐to‐severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: −1.38, 95% CI: −2.05, −0.71), food insecurity was associated with lower social scores (adjusted coeff: −0.37, 95% CI: −0.73, −0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: −0.76, 95% CI: −1.40, −0.13) and gross motor scores (adjusted coeff: −1.07, 95% CI: −1.81, −0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: −0.51, 95% CI: −1.01, −0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: −0.45, 95% CI: −0.87, −0.03) or a deceased or absent father (adjusted coeff: −0.81, 95% CI: −1.58, −0.05), respectively. Conclusions Biologic and social factors were associated with child neurodevelopment. Despite socio‐demographic differences between CHEU and CHUU, 1‐year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU.

Abstract Background The prevalence of vitamin D deficiency is high among pregnant women. Vitamin D deficiency in pregnancy is associated with increased risk of adverse pregnancy outcomes especially complications related to placental dysfunction and insulin resistance. The objective of this study is to investigate if a higher dose of vitamin D supplementation in pregnancy reduces the prevalence of vitamin D deficiency and prevents adverse pregnancy outcome with special emphasize on preeclampsia, foetal growth restriction and gestational diabetes. Methods GRAVITD is a double-blinded randomised trial with parallel groups where all pregnant women attending the free of charge national nuchal translucency scan programme in gestational week 10–14 at Randers Regional Hospital are invited to participate. Enrolment started in June 2020. Participants are randomised in a two armed randomization with a 1:1 allocation ratio into 1) control group – receives 10 µg of vitamin D or 2) intervention group – receives 90 µg of vitamin D. A total of 2000 pregnant women will be included. Maternal blood samples and questionnaires describing life-style habits are collected upon enrolment. For half of the participants blood samples and questionnaires will be repeated again in 3rd trimester. Blood samples will be analysed for 25-hydroxy-vitamin D using high-performance liquid chromatography coupled with tandem mass spectrometry. Upon delivery, placental tissue and umbilicalcord blood will be collected and information on maternal and fetal outcomes will be exstracted from medical records. The primary outcomes are serum levels of 25-hydroxy-vitamin D ≥ 75 nmol/L and the rate of preeclampsia, foetal growth restriction and gestational diabetes. Secondary outcome includes identification and impact on placental functions related to vitamin D. A tertiary outcome is to initiate a cohort of children born from mothers in the trial for future follow-up of the effects of vitamin D on childhood health. Discussion Provided that this trial finds beneficial effects of a higher dose of vitamin D supplementation in pregnancies, official recommendations can be adjusted accordingly. This will provide a low-cost and easily implementable adjustment of prenatal care which can improve health for both mother and child during pregnancy and beyond. Trial registration ClinicalTrial.gov: NCT04291313 . Registered February 17, 2020

Objectives : Aortic dilatation and regurgitation after surgical repair of tetralogy of Fallot (TOF) is known, and beside other factors, mainly addressed to an intrinsic aortopathy. In 2011, we reported the influence of realingement of the left ventricular outflow tract (LVOT) by (partial) direct closure of the ventricular septal defect (VSD) in TOF on aortic structures and function. We now evaluated the further follow-up of this cohort and compared the results to a matched group of TOF patients with classical VSD patch closure. Patients and Methods : Forty patients with TOF treated between 2003 and 2008 are included in the study, with 20 patients each in the VSD (a) (partial) direct closure and (b) patch closure group. Follow-up time after surgery was 12.3 years (11.3–13.0). Results : Patient characteristics, echocardiographic measurements, and surgical and intensive care unit parameters were not significantly different between both groups. After surgery and during long-term follow-up, realignement of the LVOT, shown by the angle between the interventricular septum and the anterior aortic annulus in long axis view in echocardiography, was lower in Group A (34 vs. 45°, P < 0.0001). No differences in LVOT or aortic annulus size, aortic regurgitation, or dilation of the ascending aorta and right ventricular outflow tract gradients were found. Transient rhythm disturbances were found in 3 patients in each group, with only one persistent complete atrioventricular block in Group B. Conclusion : (Partial) direct closure of the VSD in TOF leads to a better realignement of the LVOT and showed comparable short- and long-term results without higher risk for rhythm disturbances during follow-up.

The majority of Canadians agree they have the right to end-of-life care in their own homes. While a palliative approach to care in the home setting has been demonstrated to be beneficial for patients and the healthcare system, it has rarely been well-integrated through an eHealth approach. Thus, in 2018, we piloted the RELIEF app, a digital symptom self-reporting tool for patients with palliative care needs. This was followed by the initiation of an extension phase of RELIEF in the home care setting. In this commentary, we share the implementation perspectives and experiences of the researchers and healthcare workers involved in this home care phase. It was mainly expressed that there were challenges with nurses feeling involved, supporting the research program, and using the technology, while patients and family caregivers had challenges using the app and cooperating with staff. We describe our lessons learned from these experiences and future changes to be enacted. A detailed report of this trial will be made available in future publications.

Angola is a tropical country with many biogeographical units and, therefore, has a high floristic diversity. Although an increasing number of floristic studies has been carried out in Angola in recent years, the country is still considered to be underinvestigated as many species being collected were previously unknown there. Several scientific groups working in different parts of Angola contributed to this paper their data from biodiversity assessments. With this we can add 67 species newly recorded for Angola, including two new generic records and five alien species, to the almost 7,300 vascular plant taxa known so far for Angola. Most of the new records for Angola are also present in different neighbouring countries, but they are little known, and their IUCN threat status has not been assessed yet. However, ongoing fieldwork and exploration are needed to complete the floristic knowledge of the understudied country.

Background: Technological advancements have rapidly increased the use of point-of-care ultrasound (POCUS) across various medical disciplines, leading to real-time information for clinicians at the bed side. However, literature reveals scant evidence of POCUS use in palliative care. The objective of this study was to examine the use of POCUS in a specialist palliative care setting. Methods: A retrospective chart review was conducted from January 2018 to June 2019 in Brampton, Canada, to evaluate characteristics of patients for whom POCUS was utilized. Patients were identified through pre-existing logs and descriptive information was collected from electronic health records, including demographic information, life-limiting diagnosis, patient assessment location, diagnosis made with POCUS, and, if applicable, volume of fluid drained. Results: We identified 126 uses of POCUS in 89 unique patients. Sixty-two patients (69.7%) had a cancer diagnosis, with patients most commonly suffering from gastrointestinal, lung, and breast pathologies. Sixty-one POCUS cases (48.4%) were in the outpatient setting. Eighty-one POCUS cases (64.3%) revealed a diagnosis of ascites and 21 POCUS cases (16.7%) revealed a diagnosis of pleural effusion. Other diagnoses made with POCUS included bowel obstruction, pneumonia, and congestive heart failure. During the study period, 52 paracentesis and 7 thoracentesis procedures were performed using POCUS guidance. Conclusion: We identified multiple indications in our specialist palliative care setting where POCUS aided in diagnosis/management of patients in both inpatient and outpatient settings. Further studies can be conducted to identify the potential benefits in symptom burden, patient and caregiver satisfaction, and health care utilization in palliative care patients receiving POCUS.

Abstract Background A growing body of literature supports the efficacy of the health–social approach for the implementation of complex interventions to enhance self-care health management among community-dwelling older adults. However, there is little research on how interventions with this approach are implemented and disseminated in a real community setting. Methods This pilot study adopted an effectiveness–implementation hybrid design to 1) evaluate the effectiveness of a community-based Health–Social Partnership Program (HSPP) and 2) explore the reach, adoption, implementation, and maintenance of the HSPP in the community. Potential participants were recruited if they were aged 60 or above, owned a smartphone, and were cognitively competent. The participants received nurse-led case management with support from a social service team. Factors that hindered or facilitated the program delivery were examined to determine the implementation outcomes and sustained effects of the program. Data were collected at pre-intervention (T1), immediately post-intervention (T2), and 3 months post-intervention (T3). Results Ninety-two older adults joined and completed the program. The recruitment rate was 76.7%. A significant interaction effect was found for the mean self-efficacy scores from T1 to T2 (Wald χ2 = 12.28, p ≤ .001). Barriers to widespread program implementation included manpower shortage, lack of experienced staff, and unpredictable environment, whereas facilitators, as suggested by the older adults, providers, and community staff members, included regular communication between the research and service teams, recruitment of participants through community centers with the support of the research team, and seamless partnership among the health–social partnership team members. Strong implementation fidelity was achieved with zero attrition rate. Conclusion Most conventional randomized controlled trials investigating the effects of community-based programs have tended to control the contextual factors rather than incorporate the program in a real setting. This pilot study was the first to use a hybrid model to test the effectiveness and outcomes of HSPP implementation. The results imply that the program has a high potential sustainability in the real-life context. Trial registration This study was registered at clinicaltrials.gov (NCT04442867; date of first registration 23/06/2020).

Abstract Contrafreeloading—working to access food that could be freely obtained—is rarely exhibited and poorly understood. Based on data from Grey parrots (Psittacus erithacus), researchers proposed a correlation between contrafreeloading and play: that contrafreeloading is more likely when subjects view the task as play. We tested that hypothesis by subjecting a relatively more playful parrot species, the kea (Nestor notabilis), to the same experimental tasks. Experiment 1 presented eight kea with container pairs holding more- or less-preferred free or enclosed food items, and examined three types of contrafreeloading: calculated (working to access preferred food over less-preferred, freely available food); classic (working to access food identical to freely available food); and super (working to access less-preferred food over preferred, freely available food). At the group level, the kea behaved similarly to the Greys: They significantly preferred calculated contrafreeloading, performed classic contrafreeloading at chance, and significantly failed to super contrafreeload. However, overall kea engaged in more contrafreeloading than Greys. Experiment 2 examined a potentially more ecologically relevant task, a choice between shelled and unshelled walnuts. No kea contrafreeloaded for nuts, whereas two of five Greys significantly preferred nut contrafreeloading and one chose at chance. We examine proximate and adaptive explanations for the performances of these differentially playful parrot species to further elucidate the role of play in contrafreeloading.

Abstract Background AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study evaluating treatment patterns, clinical effectiveness, and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with neovascular age-related macular degeneration (nAMD). Methods Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 55 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica, and Mexico. Patients received IVT-AFL in a routine clinical practice setting. Results Of 274 patients in the full analysis set, 201 were treatment-naïve and 73 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections received by month 12 was 4.2 ± 1.9 (treatment-naïve) and 5.2 ± 2.7 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.2 months (treatment-naïve) and 19.5 months (previously treated). Mean best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) improved from baseline to month 12 by + 5.2 ± 18.3 (treatment-naïve; baseline: 48.2 ± 23.5) and + 3.1 ± 15.3 letters (previously treated; baseline: 47.7 ± 21.4). Conclusion AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Mean BCVA and other visual acuity outcomes improved in both treatment groups, despite many patients not receiving the IVT-AFL label-recommended regimen of three initial monthly doses, or seven or more injections in 12 months. Patients who did receive the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with nAMD treated regularly and more frequently with IVT-AFL, therefore, have the potential to achieve outcomes consistent with those observed in interventional studies. Trial registration: Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103

Abstract Eruca vesicaria subsp. sativa is a leafy vegetable of the Brassicaceae family known for its pungency. Variation in growing conditions, leaf age, agronomic practices, and variety choice lead to inconsistent quality, especially in content of isothiocyanates (ITCs) and their precursor glucosinolates (GSLs). We present the first linkage and Quantitative Trait Loci (QTL) map for Eruca, generated using a population of 139 F4 lines. A significant environmental effect on the abundance of primary and secondary metabolites was observed, with UK-grown plants containing significantly higher concentrations of glucoraphanin, malic acid, and total sugars. Italian-grown plants were characterized by higher concentrations of glucoerucin, indolic GSLs, and low monosaccharides. 20 QTL were identified and associated with robust SNP markers. Five genes putatively associated with the synthesis of the GSL 4-methoxyglucobrassicin (4MGB) were identified as candidate regulators underlying QTL. Analysis revealed that orthologs of MYB51, IGMT1 and IGMT4 present on LG1 are associated with 4MGB concentrations in Eruca. This research illustrates the utility of the map for identifying genes associated with nutritional composition in Eruca and its value as a genetic resource to assist breeding programs for this leafy vegetable crop.

ABSTRACTAs an established spatial analytical tool, Geographically Weighted Regression (GWR) has been applied across a variety of disciplines. However, its usage can be challenging for large datasets, which are increasingly prevalent in today’s digital world. In this study, we propose two high-performance R solutions for GWR via Multi-core Parallel (MP) and Compute Unified Device Architecture (CUDA) techniques, respectively GWR-MP and GWR-CUDA. We compared GWR-MP and GWR-CUDA with three existing solutions available in Geographically Weighted Models (GWmodel), Multi-scale GWR (MGWR) and Fast GWR (FastGWR). Results showed that all five solutions perform differently across varying sample sizes, with no single solution a clear winner in terms of computational efficiency. Specifically, solutions given in GWmodel and MGWR provided acceptable computational costs for GWR studies with a relatively small sample size. For a large sample size, GWR-MP and FastGWR provided coherent solutions on a Personal Computer (PC) with a common multi-core configuration, GWR-MP provided more efficient computing capacity for each core or thread than FastGWR. For cases when the sample size was very large, and for these cases only, GWR-CUDA provided the most efficient solution, but should note its I/O cost with small samples. In summary, GWR-MP and GWR-CUDA provided complementary high-performance R solutions to existing ones, where for certain data-rich GWR studies, they should be preferred.

Příspěvek seznamuje s výsledky povrchového průzkumu a geodeticko-topografického zaměření zaniklé středověké vesnice Zábdiší (k. ú. Drozdov), která náležela roku 1336 k panství hradu Žebrák. Celkem bylo zjištěno a zdokumentováno 29 antropogenních tvarů reliéfu představujících relikty obytných a hospodářských staveb. Sídelní forma byla interpretována jako návesní s devíti až deseti usedlostmi. Nálezy pozdně středověké až raně novověké keramiky získané povrchovými sběry zpřesňují dobu založení a zániku vesnice v intervalu od konce 13. do počátku 16. století. Pozornost je věnována také širšímu zázemí vesnice (extravilán), kde pomocí dat leteckého laserového skenování (LiDAR) a pozemního ověření byly identifikovány pozůstatky plužin, úvozů a milířišť. Ves je studována v širším sídelním kontextu panství hradu Žebrák, přičemž byly nově upřesněny polohy dalších dvou zaniklých vsí.

Soybean is an important global source of plant-based protein. A persistent trend has been observed over the past two decades that soybeans grown in western Canada have lower seed protein content than soybeans grown in eastern Canada. In this study, 10 soybean genotypes ranging in average seed protein content were grown in an eastern location (control) and three western locations (experimental) in Canada. Seed protein and oil contents were measured for all lines in each location. RNA-sequencing and differential gene expression analysis were used to identify differentially expressed genes that may account for relatively low protein content in western-grown soybeans. Differentially expressed genes were enriched for ontologies and pathways that included amino acid biosynthesis, circadian rhythm, starch metabolism, and lipid biosynthesis. Gene ontology, pathway mapping, and quantitative trait locus (QTL) mapping collectively provide a close inspection of mechanisms influencing nitrogen assimilation and amino acid biosynthesis between soybeans grown in the East and West. It was found that western-grown soybeans had persistent upregulation of asparaginase (an asparagine hydrolase) and persistent downregulation of asparagine synthetase across 30 individual differential expression datasets. This specific difference in asparagine metabolism between growing environments is almost certainly related to the observed differences in seed protein content because of the positive correlation between seed protein content at maturity and free asparagine in the developing seed. These results provided pointed information on seed protein-related genes influenced by environment. This information is valuable for breeding programs and genetic engineering of geographically optimized soybeans.

AimsTo appraise and synthesize qualitative studies examining older Asian people’s experiences of suicidal ideation.DesignQualitative review and meta-aggregation.Data sourcesFour databases were accessed to retrieve papers published between 1990 and 2022 including the grey literature, hand-searching of reference lists of retrieved papers and key journals. The phenomenon of interest included participants older than 60 years old, must have experienced a form of suicidal ideation and/or an unsuccessful attempt, had actively thought about harming themselves and be of Asian ethnicity.Review methodsThis review was conducted according to Consolidated Criteria for Reporting Qualitative Research and the Joanna Briggs Institute’s System for the Unified Management of the Assessment and Review of Information.ResultsOf the 289 potential studies, seven papers met the inclusion criteria. Two synthesized findings resulted from this review–The Suffering Situation: A Life without Meaning in Older Age and The Healing Situation: A Life Worth Living. The experiences of older Asian people varied from feelings of loneliness, despair and isolation to wanting to live a fruitful life into old age.ConclusionSuicidal ideation in the older person is a growing concern especially with the rise in suicide in this age group. Rising health care costs and erosion of traditional family values means that the older person views themselves as a burden. However, because of the limited number of qualitative studies from an Asian perspective it is difficult to ascertain the full extent of the issues surrounding suicide in older people.

In Canada, the length of the frost-free season necessitates planting crops as early as possible to ensure that the plants have enough time to reach full maturity before they are harvested. Early planting carries inherent risks of cold water imbibition (specifically less than 4°C) affecting seed germination. A marker dataset developed for a previously identified Canadian soybean GWAS panel was leveraged to investigate the effect of cold water imbibition on germination. Seed from a panel of 137 soybean elite cultivars, grown in the field at Ottawa, ON, over three years, were placed on filter paper in petri dishes and allowed to imbibe water for 16 hours at either 4°C or 20°C prior to being transferred to a constant 20°C. Observations on seed germination, defined as the presence of a 1 cm radicle, were done from day two to seven. A three-parameter exponential rise to a maximum equation (3PERM) was fitted to estimate germination, time to the one-half maximum germination, and germination uniformity for each cultivar. Genotype-by-sequencing was used to identify SNPs in 137 soybean lines, and using genome-wide association studies (GWAS - rMVP R package, with GLM, MLM, and FarmCPU as methods), haplotype block analysis, and assumed linkage blocks of ±100 kbp, a threshold for significance was established using the qvalue package in R, and five significant SNPs were identified on chromosomes 1, 3, 4, 6, and 13 for maximum germination after cold water imbibition. Percent of phenotypic variance explained (PVE) and allele substitution effect (ASE) eliminated two of the five candidate SNPs, leaving three QTL regions on chromosomes 3, 6, and 13 (Chr3-3419152, Chr6-5098454, and Chr13-29649544). Based on the gene ontology (GO) enrichment analysis, 14 candidate genes whose function is predicted to include germination and cold tolerance related pathways were identified as candidate genes. The identified QTLs can be used to select future soybean cultivars tolerant to cold water imbibition and mitigate risks associated with early soybean planting.

El presente artículo tiene como objetivo dar a conocer un caso de estudio donde se aplicaron metodologías para la excavación de restos de vertebrados fósiles en áreas acotadas, en el marco del proceso de monitoreo ambiental en Chile. Este caso resulta de particular interés debido a que se realizó bajo condiciones de alta humedad, durante un periodo de aproximadamente un mes en el que se procesaron ocho toneladas de sedimento. La metodología aplicada consistió en la excavación manual de niveles fosilíferos a través de desmonte lateral de planos horizontales con cuadrículas, desde los niveles superiores hasta la base del estrato portador, con recuperación de fósiles por medio de excavación de planta y bochón seco. Adicionalmente se aplicó la metodología estándar, de acuerdo con el organismo estatal, para la recuperación de microvertebrados mediante lavado y tamizado. Todo el proceso de rescate permitió la extracción de 82 piezas de las cuales el 76% fueron recuperadas in situ, mientras que el 24% fue recuperada por la metodología estándar. En base en lo anterior, se ofrecen recomendaciones para mejorar las propuestas metodológicas para rescate y monitoreo ambiental, ofreciendo una base comparativa para evaluar la efectividad de las técnicas empleadas en futuras labores de rescate.

Background: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD. Our aim is to investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC). Methods: In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months. Results: The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 h) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77–5.01, p

In this data paper, we present a specimen-based occurrence dataset compiled in the framework of the Conservation of Endemic Central African Trees (ECAT) project with the aim of producing global conservation assessments for the IUCN Red List. The project targets all tree species endemic or sub-endemic to the Central African region comprising the Democratic Republic of the Congo (DR Congo), Rwanda, and Burundi. The dataset contains 6361 plant collection records with occurrences of 8910 specimens from 337 taxa belonging to 153 genera in 52 families. Many of these tree taxa have restricted geographic ranges and are only known from a small number of herbarium specimens. As assessments for such taxa can be compromised by inadequate data, we transcribed and geo-referenced specimen label information to obtain a more accurate and complete locality dataset. All specimen data were manually cleaned and verified by botanical experts, resulting in improved data quality and consistency.

The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium.

Abstract Background AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study to understand treatment patterns and to evaluate the clinical effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with diabetic macular edema (DME). Methods Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 18 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica and Mexico. Patients received IVT-AFL in a routine clinical practice setting. Results Of 258 patients in the full analysis set, 181 were treatment-naïve and 77 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections by Month 12 was 3.7 ± 1.8 (treatment-naïve) and 4.0 ± 2.2 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.8 months (treatment-naïve) and 16.0 months (previously treated). Mean best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letters) improved from baseline to Month 12 by + 8.1 ± 17.7 (treatment-naïve; baseline: 54.5 ± 19.4) and + 4.6 ± 15.4 letters (previously treated; baseline: 52.9 ± 18.6). Conclusion AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Despite few patients being treated with the label-recommended regimen of 5 initial monthly doses or receiving ≥ 8 injections in 12 months, functional and anatomic visual outcomes improved during 12 months of treatment with IVT-AFL. Patients receiving the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with DME treated regularly and more frequently with IVT-AFL therefore have the potential to achieve outcomes consistent with those observed in interventional studies. Trial registration Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103

Abstract Background Stereotactic irradiation is one of the treatment modalities for intraocular uveal melanoma. The study’s purpose was to describe the background of stereotactic one-day session radiosurgery, how the comparison in the difference between the tumor volume measured values from the magnetic resonance imaging (MRI) method and the ultrasound method was related to it, and which method was more precise to be used for tumor regression after irradiation. Methods The group of 147 patients with choroidal melanoma was treated by stereotactic irradiation on the linear accelerator with a single dose of 35.0 Gy. During the standard treatment process the uveal melanoma volumes, needed for dose calculation, were obtained using MRI from the individual stereotactic planning scheme and by ultrasound from the ultrasound device. All volumes were statistically compared using the paired t-test, and for the visualization purpose, the Bland-Altman plot was used. Results In the group of patients, it was 70 (47.6%) males and 77 (52.4%) females. The tumor volume median was from MRI equal to 0.44 cm3 and from ultrasound equal to 0.53 cm3. The difference between the ultrasound and the MRI volume measured values was statistically significant. However, the Bland-Altman plot clearly documents that the two methods are in agreement and can be used interchangeably. In most of the cases, the measured values of the ultrasound-calculated volume achieved slightly higher measured values. Conclusions The calculation of the intraocular uveal tumor volume is a crucial part of the stereotactic irradiation treatment. The ultrasound volume measured values were in most of the cases higher than the measured values from the MRI. Although the methods are comparable and can be used interchangeably, we are recommending using the more precise MRI method not only during the treatment but also on later regular medical checks of tumor regression or progression.

Abstract Background Increased intensity of pyrethroid resistance is threatening the effectiveness of insecticide-based interventions to control malaria in Africa. Assessing the extent of this aggravation and its impact on the efficacy of these tools is vital to ensure the continued control of major vectors. Here we took advantage of 2009 and 2014 data from Malawi to establish the extent of the resistance escalation in 2021 and assessed its impact on various bed nets performance. Methods Indoor blood-fed and wild female Anopheles (An) mosquitoes were collected with an electric aspirator in Chikwawa. Cocktail and SINE PCR were used to identify sibling species belonging to An. funestus group and An. gambiae complex. The susceptibility profile to the four classes of insecticides was assessed using the WHO tubes bioassays. Data were saved in an Excel file. Analysis was done using Vassarstats and figures by Graph Pad. Results In this study, a high level of resistance was observed with pyrethroids (permethrin, deltamethrin and alpha-cypermethrin with mortality rate at 5x discriminating concentration (DC)

Information and communication technologies (ICT), such as mobile games, can potentially decrease social isolation by facilitating online and offline connections. Pokémon Go uses persuasive game elements to encourage players to walk outside and meet with fellow players during live events. In this study, we take the preliminary step of examining public opinions surrounding mobile gaming by older people. We analyzed online social media comments from a news story about Mrs. Chen, a 79-year-old woman with terminal cancer who played Pokémon Go in Taiwan. Three major themes were extracted: logistics of Pokémon Go, opinions of emotion or attitudes toward the news story, and opinions relating to older people playing games. The public was positive toward older people playing mobile games, while age-related stigmatization was found. The study's generalizability was limited by presenting a single case from Taiwan. Further studies are needed to confirm the findings.

Members of the Erwiniaceae family very rarely cause infections in humans. Here we describe the first case of a bloodstream infection due to Mixta hanseatica sp. nov., a novel member of the Erwiniaceae family.

An experimental vignette study examined whether three specific situational cues predict ways of coping with violated expectations. The situational cues (consistency, distinctiveness, consensus) were derived from the Covariation Principle. The assessed coping strategies were based on the ViolEx Model—assimilation (activities to fulfill one’s expectation), accommodation (expectation change) and immunization (ignoring the discrepant information). A sample of 124 adults (mean age = 23.60 years; 49.19 percent psychology students) were randomly assigned to an experimental and control condition. Participants of the experimental condition read several vignettes about expectation violations with systematically manipulated situational cues, while participants of the control condition received the same vignettes without such cues. Participants had to rate the usefulness of each coping strategy per vignette. The situational cues mostly led to response shifts in coping tendencies: Situations with low consistency cues mostly led to immunization, whereas high consistency led to assimilation in the case of high distinctiveness and to accommodation in the case of low distinctiveness. Consensus cues only played a minor part in the coping process. The results show that situational characteristics influence people’s coping behavior, regardless of their dispositional preferences for certain coping strategies.

A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.

IntroductionThe video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It’s usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR.Purpose (Aim)To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT.MethodsWe enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test–retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane.ResultsPooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test–retest repeatability coefficient was 0.06.ConclusionOur study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes.

ABSTRAK PLTS merupakan salah satu pembangkit yang dapat diterapkan di lingkungan perkotaan dengan memanfaatkan atap gedung sebagai lokasi pemasangannya. Salah satu lokasi yang berpotensi untuk dilakukan pemasangan PLTS adalah pada atap gedung perkantoran PT. PLN (Persero) UPT Cirebon yang memiliki luas total atap sebesar 3.150,65 m2. Desain PLTS pada lokasi penelitian dibuat menggunakan software PVSOL dengan menguji tiga skenario yaitu: penggunaan 13 inverter, 9 inverter dan optimalisasi sudut dengan 9 inverter. Dari hasil simulasi pemasangan PLTS atap pada lokasi penelitian menggunakan PVSOL didapatkan hasil produksi energi sebesar 376.354,87-386.934,28 kWh per tahun, persentase IRR sebesar 13,94%-14,35% dan penurunan emisi sebesar 272,828-280,498Â kgCO2 per tahun, yang selanjutnya akan diolah menggunakan metode weight score untuk menentukan skenario terbaik yang dapat diterapkan di lokasi penelitian. Dari hasil pengolahan data menggunakan metode weight score didapatkan skenario tiga merupakan skenario terbaik (dengan nilai 0,335) yang dapat diterapkan di lokasi penelitian. Kata kunci: PLTS atap, gable roof, weight score, PVSOL Â ABSTRACT A solar power plant is one of the power generators in an urban environment which does not need large land assets by utilizing a building roof as the installation place. One of the potential installation places is the roof of the PT. PLN (Persero) UPT Cirebon office building which has a total roof area of 3,150.65 m2. The design of the solar power plant was made using PVSOL software using 3 scenarios, which are: 9 inverters, 13 inverters, and optimizing angles with 9 inverters. From the simulation results, it is observed that the energy production results are 376,354.87-386,934.28 kWh per year, the IRR percentage is 13.94%-14.35% and the emission reduction is 272,828-280,498 kgCO2 per year. To define the best scenario from the above results, weight score method were employed whereby scenario three is the best scenario (with a score of 0.335) that can be applied at the location. Keywords: Rooftop solar power plant, gable roof, weight score, PVSOL

Introduction Childhood sexual abuse (CSA) is a global public health problem with potentially severe health and mental health consequences. Healthcare professionals (HCPs) should be familiar with risk factors and potential indicators of CSA, and able to provide appropriate medical management. The WHO issued global guidelines for the clinical care of children with CSA, based on rigorous review of the evidence base. The current systematic review identifies existing CSA guidelines issued by government agencies and academic societies in the European Region and assesses their quality and clarity to illuminate strengths and identify opportunities for improvement.Methods and analysis This 10-database systematic review will be conducted according to the Centre for Reviews and Dissemination guidelines and will be reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Guidance for HCPs regarding CSA, written by a national governmental agency or academic society of HCPs within 34 COST Action 19106 Network Countries (CANC) and published in peer-reviewed or grey literature between January 2012 and November 2022, is eligible for inclusion. Two independent researchers will search the international literature, screen, review and extract data. Included guidelines will be assessed for completeness and clarity, compared with the WHO 2017/2019 guidelines on CSA, and evaluated for consistency between the CANC guidelines. The Appraisal of Guidelines for Research and Evaluation II tool and Grading of Recommendations Assessment, Development and Evaluation methodology will be used to evaluate CANC guidelines. Descriptive statistics will summarise content similarities and differences between the WHO guidelines and national guidelines; data will be summarised using counts, frequencies, proportions and per cent agreement between country-specific guidelines and the WHO 2017/2019 guidelines.Ethics and dissemination There are no individuals or protected health information involved and no safety issues identified. Results will be published in a peer-reviewed medical journal.PROSPERO registration number CRD42022320747.

Summary: Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy. Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.

Healthcare innovations emerge and develop in institutionally dense selective environments. New projects and propositions in healthcare sectoral ecosystems can be understood as product-service compacts, that is, complex solutions that dynamically integrate tangible and intangible elements in close interaction with users’ needs and the evolving regulatory context under uncertainty and ambiguity. We advance the concept of “strategic encounters” to encapsulate, capitalise and extend the contribution by Palm and Fischier’s on the key enabling managerial factors for healthcare innovation implementation under conditions of imperfect foresight. We intertwine creative assemblages that shape the formation of knowledge-intensive activities at the operators’ level with scope of sectoral level interventions to underscore how the opportunities and constraints can enhance innovation for the common good. We use the case of digital data health regulatory agendas as illustration. We argue that this broader perspective on healthcare transformation is theoretically pertinent and practically useful, for management and policy.

Abstract Objective Most of the previous risk prediction models for lung cancer were developed from smokers, with discriminatory power ranging from 0.57 to 0.72. We constructed an individual risk prediction model for lung cancer among the male general population of Hong Kong. Methods Epidemiological data of 1,069 histology confirmed male lung cancer cases and 1,208 community controls were included in this analysis. Residential radon exposure was retrospectively reconstructed based on individual lifetime residential information. Multivariable logistic regression with repeated cross-validation method was used to select optimal risk predictors for each prediction model for different smoking strata. Individual absolute risk for lung cancer was estimated by Gail model. Receiver-operator characteristic curves, area under the curve (AUC) and confusion matrix were evaluated to demonstrate the model performance and ability to differentiate cases from non-cases. Results Smoking and smoking cessation, education, lung disease history, family history of cancer, residential radon exposure, dietary habits, carcinogens exposure, mask use and dust control in workplace were selected as the risk predictors for lung cancer. The AUC of estimated absolute risk for all lung cancers was 0.735 (95% CI: 0.714–0.756). Using 2.83% as the cutoff point of absolute risk, the predictive accuracy, positive predictive value and negative predictive value were 0.715, 0.818 and 0.674, respectively. Conclusion We developed a risk prediction model with moderate discrimination for lung cancer among Hong Kong males. External validation in other populations is warranted for this model in future studies.

Patients with arterial hypertension have an increased risk of developing tumors, particularly renal cell carcinoma. Arterial hypertension is linked to DNA damage via the generation of oxidative stress, in which an upregulated renin–angiotensin–aldosterone system plays a crucial role. The current study investigated surrogates of oxidative stress and DNA damage in a group of hypertensive patients (HypAll, n = 64) and subgroups of well (HypWell, n = 36) and poorly (HypPoor, n = 28) controlled hypertensive patients compared to healthy controls (n = 8). In addition, a longitudinal analysis was performed with some of the hypertensive patients. Markers for oxidative stress in plasma (SHp, D-ROM, and 3-nitrotyrosine) and urine (8-oxodG, 15-F2t-isoprostane, and malondialdehyde) and markers for DNA damage in lymphocytes (γ-H2AX and micronuclei) were measured. In HypAll, all markers of oxidative stress except malondialdehyde were increased compared to the controls. After adjustment for age, this association was maintained for the protein stress markers SHp and 3-nitrotyrosine. With regard to the markers for DNA damage, there was no difference between HypAll and the controls. Further, no significant differences became apparent in the levels of both oxidative stress and DNA damage between HypWell and HypPoor. Finally, a positive correlation between the development of blood pressure and oxidative stress was observed in the longitudinal study based on the changes in D-ROM and systolic blood pressure. In conclusion, we found increased oxidative stress in extensively treated hypertensive patients correlating with the level of blood-pressure control but no association with DNA damage.

A rapid decrease in viral gastroenteritis during winter 2019–20 and a return of norovirus and rotavirus activity during winter 2020–21 were observed while multiple nonpharmaceutical interventions for coronavirus disease were in effect in Hong Kong. The initial collateral benefit of coronavirus disease countermeasures that reduced the viral gastroenteritis burden is not sustainable.

Objective: Pathogen detection is crucial for diagnosis and targeted therapy in implant-associated bone and joint infections (BJI). Culture-based microbiology regularly fails to identify causative pathogens. This study evaluated the diagnostic accuracy and clinical usefulness of a syndromic panel polymerase chain reaction (spPCR) assay targeting common BJI pathogens in tissue specimens from patients with implant-associated BJI. Methods: Results obtained by spPCR assay and a 16S rDNA PCR were compared with results obtained from a standard of care (SOC) culture-based diagnostics, serving as a gold standard. In total, 126 specimens obtained from 73 patients were analyzed. Results: The spPCR assay correctly identified 33/40 culture-positive samples (82.5 %) and was positive in 9/86 (10.5 %) culture-negative samples, resulting in an overall sensitivity of 84.6 % (95% confidence interval [CI] 68.79-93.59%) and specificity of 89.35% (95% CI 80.6-94.81%). The spPCR was more sensitive compared with the 16S rDNA PCR (37.5%). The spPCR identified pathogens in 7/51 (13.7%) SOC-negative patients. Re-evaluation of spPCR results in clinical context suggested their clinical significance. Conclusion: An spPCR assay targeting common pathogens causing implant-associated BJI may help to identify causative agents in culture-negative cases. As false-negative results are possible, spPCR assays appear as an add-on approach for pathogen detection in implant-associated BJI.

Abstract Though saccade and vergence eye movements are fundamental for everyday life, the way these movements change as we age has not been sufficiently studied. The present study examines the effect of age on vergence and saccade eye movement characteristics (latency, peak and average velocity, amplitude) and on audiovisual facilitation. We compare the results for horizontal saccades and vergence movements toward visual and audiovisual targets in a young group of 22 participants (mean age 25 ± 2.5) and an elderly group of 45 participants (mean age 65 + 6.9). The results show that, with increased age, latency of all eye movements increases, average velocity decreases, amplitude of vergence decreases, and audiovisual facilitation collapses for vergence eye movements in depth but is preserved for saccades. There is no effect on peak velocity, suggesting that, although the sensory and attentional mechanisms controlling the motor system does age, the motor system itself does not age. The loss of audiovisual facilitation along the depth axis can be attributed to a physiologic decrease in the capacity for sound localization in depth with age, while left/right sound localization coupled with saccades is preserved. The results bring new insight for the effects of aging on multisensory control and attention.