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Background: Time-to-event analysis is associated with methodological complexities. Previous research identified flaws in the reporting of time-to-event analyses in randomized trial publications. These hardships impose challenges for meta-analyses of time-to-event outcomes based on aggregate data. We examined the characteristics, reporting and methods of systematic reviews including such analyses. Methods: Through a systematic search (02/2017-08/2020), we identified 50 Cochrane Reviews with ≥ 1 meta-analysis based on the hazard ratio (HR) and a corresponding random sample (n = 50) from core clinical journals (Medline; 08/02/2021). Data was extracted in duplicate and included outcome definitions, general and time-to-event specific methods and handling of time-to-event relevant trial characteristics. Results: The included reviews analyzed 217 time-to-event outcomes (Median: 2; IQR 1–2), most frequently overall survival (41%). Outcome definitions were provided for less than half of time-to-event outcomes (48%). Few reviews specified general methods, e.g., included analysis types (intention-to-treat, per protocol) (35%) and adjustment of effect estimates (12%). Sources that review authors used for retrieval of time-to-event summary data from publications varied substantially. Most frequently reported were direct inclusion of HRs (64%) and reference to established guidance without further specification (46%). Study characteristics important to time-to-event analysis, such as variable follow-up, informative censoring or proportional hazards, were rarely reported. If presented, complementary absolute effect estimates calculated based on the pooled HR were incorrectly calculated (14%) or correct but falsely labeled (11%) in several reviews. Conclusions: Our findings indicate that limitations in reporting of trial time-to-event analyses translate to the review level as well. Inconsistent reporting of meta-analyses of time-to-event outcomes necessitates additional reporting standards. [ABSTRACT FROM AUTHOR]

Restoration engineering measures, such as managed realignments or building groins, modify the environmental characteristics of coastal intertidal ecosystems. Creating physical modifications that are beneficial to an intertidal system's ecology necessitates an in‐depth understanding of the relationships between the abiotic and biotic components of a given intertidal habitat. In this study, we evaluate how hydrodynamics and sediment characteristics drive the development of the benthic macrofauna community during the first 5 years following engineering measures to enhance benthic macrofauna diversity at three locations. The creation of low‐energy habitats through groins (Knuitershoek and Baalhoek) and a managed realignment dike breach (Perkpolder) led to the accumulation of fine sediments in all three impact sites. Biomass of benthic macrofauna quickly increased between 2016 and 2020, with successional processes being more important in Perkpolder, where the habitat was started completely from scratch due to a managed realignment, than at Knuitershoek or Baalhoek, where habitat conditions were improved by adding groins. In addition, the density of benthos‐eating birds, especially oystercatchers, increased at some of the modified sites. While a low‐energy habitat may harbor more diverse assemblages of benthic macrofauna than a highly dynamic one, the extremely high silt content, which is typical for low‐energy habitats, may slow benthic community development. The observed increase of biomass at our impact sites highlights the value of the interventions, while the delays in the response of the benthic macrofauna community emphasizes the need for extensive monitoring both in time and space and the identification of underlying abiotic–biotic mechanisms. [ABSTRACT FROM AUTHOR]

Tidal flats are valuable ecosystems that depend on complex biogeomorphic processes between organisms and sediment transport. Climate change has led to a rise in extreme weather events, such as storms. This, in turn, has increased sediment dynamics and created risks for the benthic communities inhabiting tidal flats. However, replicating sediment disturbances caused by extreme weather is difficult. To overcome this, we used the plow rake to enhance the natural tidal currents and wave conditions to simulate intensified sediment dynamics. The raking disturbance was repeated on two intertidal zones with different inundation frequencies and wind fetch levels to simulate the increasing frequency of storm impact on sediments due to climate change. We compared the measurements of sediment dynamics and macrofauna between plots that were raked and the control plots that were only influenced by natural hydrodynamics. Results showed that tidal flat sediments experienced erosion by 10–20 mm after six times biweekly raking treatments, depending on the site‐specific hydrodynamic conditions. Sediment dynamics served as a helpful tool for monitoring the species distribution regarding mobility traits: the high dynamic exposed sites were inhabited by mobile species, while the low dynamic sheltered sites were characterized by less‐mobile species. Moreover, the raking treatment decreased the abundance of species with immobile traits, yet the species composition did not experience significant change. Overall, the present findings indicate that tidal flats with low sediment dynamics and immobile macrofauna are at higher risk of declining abundance under intensified sediment disturbances than areas with high sediment dynamics and mobile macrofauna. [ABSTRACT FROM AUTHOR]

Purpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors. Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963–2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer–Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1–5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p < 0.004). Results: CCS, N = 1713, age mean (M) 36 years, 49% female, ≥ 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact. Conclusion and implications: The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support. [ABSTRACT FROM AUTHOR]

Background: We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. Methods: In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. Results: Mean age was 58 ± 11 years, 76% were men, 82% were in NYHA class I/II, mean LASr was 20.9% ± 11.3%, and mean LVEF was 29% ± 10%. PEP was reached by 50 patients. Baseline and repeated measurements of LASr (HR per SD change (95% CI) 0.20 (0.10–0.41) and (0.13 (0.10–0.29), respectively) were both significantly associated with the PEP, independent of both baseline and repeated measurements of other echo-parameters and NT-proBNP. Although LASr was persistently lower over time in patients with PEP, temporal trajectories did not diverge in patients with versus without the PEP as the PEP approached. Conclusion: LASr was associated with adverse events in HFrEF patients, independent of baseline and repeated other echo-parameters and NT-proBNP. Temporal trajectories of LASr showed decreased but stable values in patients with the PEP, and do not provide incremental prognostic value for clinical practice compared to single measurements of LASr. [ABSTRACT FROM AUTHOR]

Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF–HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF–HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions. [ABSTRACT FROM AUTHOR]

Striking large‐scale spatial patterns in ecosystems, generated by self‐organization through biotic and abiotic feedback processes, influence ecosystem functioning and response to global environmental change. A remarkable example of this are the regular ridge‐runnel patterns found on tidal flats, which play an important role in mudflat‐marsh transitions. Yet the mechanisms driving their formation, and whether they are abiotic or biotic in origin, have not been elucidated. The underlying mechanisms are unraveled in this study through a combination of field measurements and targeted laboratory experiments. In the field, we find that on the ridges of the pattern, the sediment bed level is less dynamic and more resistant to erosion than in the runnels. In laboratory flume experiments, we find that erosion‐resistant surfaces, like those found on the ridges, can arise on time scales of hours to days due to the drying of the cohesive sediment bed, while this is prevented in waterlogged sediments in runnels. A disturbance‐recovery experiment on benthic algae then confirms that biological processes require a longer developmental period than the time scale at which we have observed drying‐induced erosion resistance to develop. Together, these results demonstrate that ridge‐runnel patterns begin from an abiotic initiation point that can subsequently provide a template for further biological establishment and self‐organization. Recognition of abiotic processes as catalysts of self‐organization can improve our understanding of ecosystem responses to environmental changes. [ABSTRACT FROM AUTHOR]

Objective: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. Methods: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video‐electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). Results: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body‐turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). Interpretation: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age‐dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138–1148 [ABSTRACT FROM AUTHOR]

In 1909, when the sultanate of Wadai, the last independent Muslim state in Africa, succumbed to French authority, the scholar ʿAbd al-Ḥaqq al-Sanūsī al-Tarjumī wrote a treatise explaining why Muslims could remain in the country and live in reconciliation (ṣulḥ) with their Christian conquerors. More than a hundred years later, the author and his treatise, Tabṣirat al-ḥayrān min hawl fitan al-zamān (Instructions for the Perplexed on the Horror of the Trials of our Time) have both acquired new reputations, with al-Tarjumī now a central figure in the sphere of oral wisdom narratives. This article explores why interest in al-Tarjumī has revived, and the relation between his work and his reputation. It argues that his scholarly plea for reconciliation with the non-Muslim colonial occupants of Wadai is re-invoked today to strengthen the position of traditional Muslims in Chad compared to that of fundamentalists. [ABSTRACT FROM AUTHOR]

Railway transition zones present a major challenge in railway track design mainly due to abrupt jumps in stiffness and differential settlements that result from crossing stiffer structures such as bridges or culverts. Despite numerous efforts to mitigate these transition effects at both the superstructure and substructure levels, a comprehensive solution remains elusive. Substructure-level interventions have demonstrated some effectiveness but are often cost-prohibitive and challenging to implement in existing operational railway transition zones. In contrast, mitigation measures at the superstructure (rail, sleepers, rail-pads, under-sleeper pads) level can be easily installed but have shown limited improvement in site measurements. This study evaluates the influence of different sleeper configurations in transition zones and reduced sleeper spacings on the operation-driven dynamic amplifications in railway transition zones, employing a recently proposed criterion based on the total strain energy in the track-bed layers (ballast, embankment, and subgrade). In addition to this, the influence of the loss of contact between sleepers and ballast (i.e., hanging sleepers), which typically results from the differential settlement, is studied. The first part of the paper provides useful insights regarding the interventions (and/or initial design) in the sleeper configuration and spacing, whereas the second part of the work highlights the need for interventions to deal with the loss of contact between sleeper and ballast. A 2-dimensional finite element model of an embankment-bridge transition was used for the analysis. The results show that it is not possible to mitigate the transition effects completely using the interventions involving sleeper spacing and configuration. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of care for selected cases of peritoneal surface malignancy. However, due to its morbidity and learning curve, it is only delivered in six centres in Australia and Aotearoa New Zealand (AoNZ). In this study, we report peri‐operative morbidity and mortality following CRS/HIPEC at Waikato and Braemar Hospitals, which have treated patients from all regions of AoNZ since 2008. Methods: We retrospectively reviewed a database of all patients undergoing CRS and HIPEC from 01/01/2008 to 01/11/2020 at Waikato and Braemar Hospitals. Results: Two‐hundred and forty procedures were performed for 221 patients with a mean age of 55, including 22 (9.2%) re‐do procedures. One hundred and eighty‐six cases were European, 32 were Māori, and 16 were Pasifika. There were 152 pseudomyxoma peritonei, 39 colorectal adenocarcinomas, 29 appendiceal cancers, 8 ovarian cancers, 6 peritoneal mesothelioma, and 6 other tumour types. The median PCI was 16. HIPEC was administered to 196 out of 196 CC0/1 cases (100%) and 3 out of 44 CC2/3 cases (6.8%). Fifty‐six cases (23.3%) had at least one major complication. There were two mortalities (0.8%) within 30 days. The median length of stay was 11 days. Operative duration was identified as an independent risk factor for major complications. There was considerable variation in the number of referrals from different regions of AoNZ. Over time, a decline in major complication rate is seen with increased case volume. Conclusion: The Waikato region has achieved favourable short‐term outcomes following CRS/HIPEC. [ABSTRACT FROM AUTHOR]

Backgrounds: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for selected cases of peritoneal surface malignancy. In 2008, a CRS/HIPEC service was first established in Aotearoa New Zealand (AoNZ) at Waikato and Braemar Hospitals in the Waikato region. Methods: This is a retrospective review of a prospectively maintained database of all patients undergoing CRS/HIPEC from 1 January 2008 to 1 November 2020 at Waikato and Braemar Hospitals. We analysed long‐term survival and predictors of survival for each tumour type. Results: 240 procedures were performed for 221 patients, including 22 re‐do procedures. Cases had a median peritoneal cancer index of 16. Complete cytoreduction (CC0‐1) was achieved in 196 cases (81.7%). All complete cytoreduction cases received HIPEC. There were 152 pseudomyxoma peritonei (PMP), 39 colorectal cancers (CRC), 29 appendiceal cancers, eight ovarian cancers, six peritoneal mesotheliomas, and six other cancers. The 5‐year overall survival (OS) for PMP with acellular mucin, low‐grade mucinous carcinoma peritonei, and high‐grade mucinous carcinoma peritonei with or without signet cells were 91.6%, 80.5%, and 72.2%, respectively. 2‐ and 5‐year OS in CRC were 56.7% and 40.4%. The achievement of complete cytoreduction improved the 5‐year OS to 87.9% across all PMP and 45.1% in colorectal cancer. Incomplete cytoreduction predicted worse survival in appendiceal PMP. In colorectal cancer, worse survival was predicted in those who had incomplete cytoreduction, liver metastasis, and presentation with obstruction and perforation. Conclusion: Favourable long‐term outcomes following CRS/HIPEC for peritoneal surface malignancy have been achieved in AoNZ through the Waikato peritonectomy service. [ABSTRACT FROM AUTHOR]

Background: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1–2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. Methods: Women diagnosed in 2013–2014 with unilateral cT1–2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi–pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. Results: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. Conclusion: In this registry study of patients with cT1–2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients with cT1–2 N0 breast cancer treated with mastectomy, who have limited sentinel lymph node involvement. The 5-year regional recurrence rate was low (overall 1.3%) and comparable between treatment groups. Omitting completion axillary treatment appears to be safe in selected patients. [ABSTRACT FROM AUTHOR]

Purpose: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. Methods: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. Results: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). Conclusion: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient. Plain English summary: Breast cancer is one of the most common cancers among women worldwide. Since the survival rates are improving, the health-related quality of life of breast cancer patients after treatment becomes more important. One of the most important factors in the prognosis of breast cancer patients is the presence of axillary metastasis, the spread of breast cancer to lymph nodes in the armpit. There are different axillary treatments which can all affect health-related quality of life negatively. Therefore, the aim of this study is to examine the effect of different axillary treatments on physical, psychosocial, and sexual wellbeing and arm symptoms of breast cancer patients. This study included women with breast cancer who received either axillary preserving surgery with or without axillary radiotherapy, or a full axillary lymph node dissection with or without axillary radiotherapy. health-related quality of life was assessed with validated breast cancer specific questionnaires at baseline, 6- and 12-months postoperatively. Patients who underwent axilla preserving surgery without axillary radiotherapy experienced significantly less decline in both physical and psychosocial wellbeing as well as significantly fewer increase in arm symptoms compared to patients who received the more extensive axillary treatments. The results of this study can be used to improve shared decision making and expectation management for future breast cancer patients.b [ABSTRACT FROM AUTHOR]

As research of benefits and detriments of pesticides and biocides progresses, people's knowledge needs to be updated. This study takes an audience perspective on how practitioners may improve communication. Through online focus group discussions of how and why Danes acquire knowledge of pesticides and biocides, we find that focusing on improving people's knowledge structures, heuristics and self-efficacy may improve people's ability to acquire such knowledge and in turn improve their motivation. This paper provides suggestions for how practitioners may create more effective communication. [ABSTRACT FROM AUTHOR]

Rhipicephalus (Boophilus) microplus, an invasive species to Africa, and the endemic R. (B.) decoloratus are of high economic importance in the cattle industry. Invasion of the alien species in South Africa has mostly been reported for traditional communal grazing areas where it seemed to be rapid and, in some cases, even replaced the native species. The alien species is also assumed to already be resistant to acaricides upon invasion. The presence of R. (B.) microplus on commercial farms was therefore investigated and resistance screening of both species to field concentrations of cypermethrin, amitraz, and chlorfenvinphos was determined by means of the larval immersion test. Results showed that only 3.7% (of 383) tick collections submitted were R. (B.) microplus populations. A further 1.6% (of 383) showed co-existence of the two species. Comparing the level of resistance to the acaricides between the two species indicated a mean phenotypic resistance of 66.2 and 26.5% of R. (B.) decoloratus populations to cypermethrin and amitraz, respectively. This was significantly lower for R. (B.) microplus, with 23.0 and 4.1% of its populations resistant to cypermethrin and amitraz, respectively. Closed commercial farming areas seemed to have a preventative advantage for the invasion of R. (B.) microplus and displacement of R. (B.) decoloratus by R. (B.) microplus. Regular monitoring of these two species may be of high importance to prevent unnecessary financial losses due to insufficient control and increased awareness of the threat of Asiatic babesiosis vectored by R. (B.) microplus. [ABSTRACT FROM AUTHOR]

Accurate standardization of left atrium volume (LAV) in patients with obesity is challenging. The aim of this study was to investigate and to examine the relation between LAV indexed to height2 and left atrial function in patients with moderate to severe obesity. Echocardiograms of patients with moderate to severe obesity (body mass index (BMI) ≥ 35 kg/m2) without known cardiac disease were analyzed. LAV was indexed to body surface area (BSA) and height2, and patients were divided into those with or without left atrial enlargement (LAE) based on normalization using either BSA (LAEbsa) or height2 (LAEh2). Using speckle tracking echocardiography, LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were assessed as a measure of LA function. LA dysfunction was defined as LASct < 14%. A total of 142 patients were included in the analysis of whom 54.2% had LAEh2 and 18.3% LAEBSA. The LAEh2 group had significantly lower LASct (12.2% ± 3.2% vs. 13.6% ± 4.5%, p = 0.019) as compared to the patients without LAEh2. Significantly more patients with LA dysfunction would be correctly identified by LAEh2 than by LAEBSA (41.5% vs. 15.0%, p < 0.001). In patients with moderate to severe obesity, the use of LAEh2 identified significantly more patients with decreased LA function. LAVh2 should be preferred over LAVBSA in patients with moderate to severe obesity. [ABSTRACT FROM AUTHOR]

Purpose: Flexible staffing arrangements have become a permanent feature of employment in many industrial societies. This article examines how employers perceive the consequences of using flexible staffing arrangements. It presents and assesses theoretically informed hypotheses on organisational situations in which negative consequences are more likely to be perceived. Design/methodology/approach: This study uses data (n = 761) from a bespoke employers survey, fielded in the Netherlands in 2019. Structural equation modelling (SEM) is used to measure and explain employers' perception of downsides to flexible staffing arrangements. Findings: Employers report distinct downsides to the use of flexible staffing arrangements in terms of performance, management and employee well-being. Model estimates show that employers using flexible staffing arrangements to acquire specific expertise or to follow other organisations in their sector perceive more downsides. Originality/value: Empirical research on employers' perception of the disadvantageous consequences of using flexible staffing arrangements is scarce. This article highlights that this practice can discourage investments in human capital and lead to a sense of insecurity among young workers. It draws attention to the relevance of distinguishing between strategic motives when trying to understand organisational behaviour regarding non-standard forms of employment. [ABSTRACT FROM AUTHOR]

Aim: Epicardial adipose tissue (EAT) plays a role in obesity‐related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. Methods and results: Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT‐1 (EAT <3.8 mm), 63 in EAT‐2 (EAT 3.8–5.4 mm), and 61 in EAT‐3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT‐3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one‐unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β coefficient −0.404, p = 0.002), and a decrease in LASct (%) (β coefficient −0.544, p = 0.027). Furthermore, EAT‐3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045). Conclusions: Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease. [ABSTRACT FROM AUTHOR]

Perimyocarditis involves inflammation of the heart muscle and surrounding tissue, causing reduced left ventricular ejection fraction. Typically viral, but occasionally bacterial, this condition can arise from Bartonella henselae, a rare yet potentially serious pathogen that can lead to cardiac inflammation and subsequent heart failure. Since this bacterium is mainly associated with cat scratch disease—which is selflimiting and has a mild disease course—B. henselae’s potential role in cardiac disease is underestimated. We present a mid-30s man, immunocompetent, who presented to the emergency department with acute heart failure due to B. henselae-associated perimyocarditis. Despite not recalling any scratches or bites from cats, the patient had been living with cats, which likely exposed him. This case highlights the varied clinical presentations of B. henselae-associated heart disease and underscores the importance of considering this pathogen as a potential cause of perimyocarditis, particularly in individuals with exposure to cats. [ABSTRACT FROM AUTHOR]

Background: Respiratory mucosal host defense relies on the production of secretory IgA (sIgA) antibodies, but we currently lack a fundamental understanding of how sIgA is induced by contact with microbes and how such immune responses may vary between humans. Defense of the nasal mucosal barrier through sIgA is critical to protect from infection and to maintain homeostasis of the microbiome, which influences respiratory disorders and hosts opportunistic pathogens. Methods: We applied IgA-seq analysis to nasal microbiota samples from male and female healthy volunteers, to identify which bacterial genera and species are targeted by sIgA on the level of the individual host. Furthermore, we used nasal sIgA from the same individuals in sIgA deposition experiments to validate the IgA-seq outcomes. Conclusions: We observed that the amount of sIgA secreted into the nasal mucosa by the host varied substantially and was negatively correlated with the bacterial density, suggesting that nasal sIgA limits the overall bacterial capacity to colonize. The interaction between mucosal sIgA antibodies and the nasal microbiota was highly individual with no obvious differences between potentially invasive and non-invasive bacterial species. Importantly, we could show that for the clinically relevant opportunistic pathogen and frequent nasal resident Staphylococcus aureus, sIgA reactivity was in part the result of epitope-independent interaction of sIgA with the antibody-binding protein SpA through binding of sIgA Fab regions. This study thereby offers a first comprehensive insight into the targeting of the nasal microbiota by sIgA antibodies. It thereby helps to better understand the shaping and homeostasis of the nasal microbiome by the host and may guide the development of effective mucosal vaccines against bacterial pathogens. 7hP8wdG6y5p5ZRVJGsDS4Z Video Abstract [ABSTRACT FROM AUTHOR]

Is the trust that participants have in their pension fund affected by its funding ratio (i.e., asset/liabilities ratio)? Based on survey, carried out in October 2021, among Dutch pension fund participants we link our survey data to the funding ratio of their pension fund as registered by the pension regulator. First, we show that the level of the funding ratio of their pension fund is positively associated with the trust level of participants. Pension funds with large buffers are associated with a high level of trust. Second, sub-group analyses show that the trust of younger participants is weakly related to the level of the funding ratio and this association is strong and positive for older (55+)/retired participants. It suggests that an interest in or awareness about the financial health of one's pension fund is associated with a higher responsiveness of participants in terms of trust. And third, firm-based pension funds enjoy a higher level of trust compared to sector-based pension funds. [ABSTRACT FROM AUTHOR]

Introduction: Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence. Methods: A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis. Results: Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0–17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors. Conclusion: Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to estimate the probability of obstructive CAD (oCAD) for an individual patient as a function of the myocardial flow reserve (MFR) measured with Rubidium-82 (Rb-82) PET in patients with a visually normal or abnormal scan. Materials and Methods: We included 1519 consecutive patients without a prior history of CAD referred for rest-stress Rb-82 PET/CT. All images were visually assessed by two experts and classified as normal or abnormal. We estimated the probability of oCAD for visually normal scans and scans with small (5%–10%) or larger defects (> 10%) as function of MFR. The primary endpoint was oCAD on invasive coronary angiography, when available. Results: 1259 scans were classified as normal, 136 with a small defect and 136 with a larger defect. For the normal scans, the probability of oCAD increased exponentially from 1% to 10% when segmental MFR decreased from 2.1 to 1.3. For scans with small defects, the probability increased from 13% to 40% and for larger defects from 45% to > 70% when segmental MFR decreased from 2.1 to 0.7. Conclusion: Patients with > 10% risk of oCAD can be distinguished from patients with < 10% risk based on visual PET interpretation only. However, there is a strong dependence of MFR on patient's individual risk of oCAD. Hence, combining both visual interpretation and MFR results in a better individual risk assessment which may impact treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart. Methods: A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed. Results: Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0–56.4%), diastolic dysfunction (30.0–100%), combinations of echocardiography and/or clinical parameters (0.0–38.1%), clinical symptoms (0.0–25.5%) and biomarker levels (0.0–37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor. Conclusions: Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The ACOSOG-Z0011- and the AMAROS-trial obviated the need for axillary surgery in most sentinel node-positive (SLN+) breast cancer patients undergoing breast-conserving surgery (BCS). Data for patients who undergo mastectomy is scarce. The purpose of this study was to investigate patterns of axillary treatment in SLN+ patients treated by mastectomy in the years after the publication of landmark studies regarding axillary treatment in SLN+ breast cancer patients undergoing BCS. Methods: This was a population-based study in cT1-3N0M0 breast cancer patients treated by mastectomy and staged as SLN+ between 2009 and 2018. The performance of an axillary lymph node dissection (ALND) and/or administration of postmastectomy radiotherapy (PMRT) were primary outcomes and were studied over time. Results: The study included 10,633 patients. The frequency of ALND performance decreased from 78% in 2009 to 10% in 2018, whereas PMRT increased from 4 to 49% (P < 0.001). In ≥N1a patients, ALND performance decreased from 93 to 20%, whereas PMRT increased to 70% (P < 0.001). In N1mi and N0itc patients, ALND was abandoned during the study period, whereas PMRT increased to 38% and 13% respectively (P < 0.001), respectively. Age, tumor subtype, N-stage, and hospital type affected the likelihood that patients underwent ALND. Conclusions: In this study in SLN+ breast cancer patients undergoing mastectomy, use of ALND decreased drastically over time. By the end of 2018 most ≥N1a patients received PMRT as the only adjuvant axillary treatment, whereas the majority of N1mi and N0itc patients received no additional treatment. [ABSTRACT FROM AUTHOR]

Purpose: In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer. Methods: In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events. Results: Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator. Conclusion: RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions. [ABSTRACT FROM AUTHOR]

Cathepsin B is a cysteine protease that is implicated in multiple aspects of Alzheimer's disease pathogenesis. The endogenous inhibitor of this enzyme, cystatin B (CSTB) is encoded on chromosome 21. Thus, individuals who have Down syndrome, a genetic condition caused by having an additional copy of chromosome 21, have an extra copy of an endogenous inhibitor of the enzyme. Individuals who have Down syndrome are also at significantly increased risk of developing early-onset Alzheimer's disease (EOAD). The impact of the additional copy of CSTB on Alzheimer's disease development in people who have Down syndrome is not well understood. Here we compared the biology of cathepsin B and CSTB in individuals who had Down syndrome and Alzheimer's disease, with disomic individuals who had Alzheimer's disease or were ageing healthily. We find that the activity of cathepsin B enzyme is decreased in the brain of people who had Down syndrome and Alzheimer's disease compared with disomic individuals who had Alzheimer's disease. This change occurs independently of an alteration in the abundance of the mature enzyme or the number of cathepsin B+ cells. We find that the abundance of CSTB is significantly increased in the brains of individuals who have Down syndrome and Alzheimer's disease compared to disomic individuals both with and without Alzheimer's disease. In mouse and human cellular preclinical models of Down syndrome, three-copies of CSTB increases CSTB protein abundance but this is not sufficient to modulate cathepsin B activity. EOAD and Alzheimer's disease-Down syndrome share many overlapping mechanisms but differences in disease occur in individuals who have trisomy 21. Understanding this biology will ensure that people who have Down syndrome access the most appropriate Alzheimer's disease therapeutics and moreover will provide unique insight into disease pathogenesis more broadly. [ABSTRACT FROM AUTHOR]

In South Africa, acaricides are widely used for tick control but very few reports are available on resistance development of Rhipicephalus (Boophilus) decoloratus Koch to chemical control on commercial farming systems in Africa, south of the Sahara. Resistance to different acaricide classes reported over the years was mostly from localised communal farming systems. This report addresses the lack of available information on resistance development by reviewing results found during a National Tick Resistance Survey carried out from 1998 to 2001, laying the foundation for more recent research on resistance development, and the evolution of resistance over the years. One hundred and eighty R. decoloratus populations were randomly collected from commercial farming systems, covering most of the provinces of South Africa. Larval immersion tests were used to determine phenotypic resistance for each tick population and 6.6% of the populations tested were found to be resistant to amitraz, 35.5% to cypermethrin, and 36.1% to chlorfenvinphos. Multi-resistance to all three acaricides was found in 1.2% of populations and a further 25.8% of the populations were resistant to two acaricides. The detection of resistance of Rhipicephalus (Boophilus) species to currently used or new acaricides is an essential tool in resistance management. The acaricides tested for the resistance of R. decoloratus during the survey are currently still in use in South Africa and these historical results, never published before, can be valuable and can act as reference data to determine the evolution of resistance development to acaricides in more recent studies. [ABSTRACT FROM AUTHOR]

The development of tick resistance to chemical control plays a major role in the increasing global economic impact of ticks on cattle farming. Reports on acaricide resistance of Rhipicephalus decoloratus, endemic to Africa and South Africa, are relatively few compared to the closely related and globally distributed Rhipicephalus microplus. In South Africa, ectoparasite control became the sole responsibility of each commercial producer when compulsory dipping was phased out from 1984. Different acaricidal management strategies resulted in the simultaneous development of resistance to various acaricide groups. The establishment of a Pesticide Resistance Testing Facility provided the opportunity to test Rhipicephalus (Boophilus) populations, submitted from all over South Africa, for resistance where failure of chemical control was experienced. The number of populations resistant to cypermethrin (CM) was significantly higher than those tested as resistant to amitraz (AM), or chlorfenvinphos (CFVP). No significant difference was found between the number of populations resistant to AM and CFVP. The evolution of R. decoloratus resistance at the end of a 12 year period indicated a stable but high prevalence of 90% overall resistance to CM. The same trend was seen for AM-resistant R. decoloratus populations but at a lower level of just over 40%. In contrast, CFVP resistant R. decoloratus populations showed a decreasing trend with near-total reversion to susceptibility. Multi-resistance was present in more than 50% of populations tested with the highest incidence in the Eastern Cape, KwaZulu-Natal, and Western Cape provinces. [ABSTRACT FROM AUTHOR]

Purpose: In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer. Methods: In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events. Results: Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator. Conclusion: RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions. [ABSTRACT FROM AUTHOR]

Introduction: Accurate risk stratification in patients with suspected stable coronary artery disease is essential for choosing an appropriate treatment strategy. Our aim was to develop and validate a machine learning (ML) based model to diagnose obstructive CAD (oCAD). Method: We retrospectively have included 1007 patients without a prior history of CAD who underwent CT-based calcium scoring (CACS) and a Rubidium-82 PET scan. The entire dataset was split 4:1 into a training and test dataset. An ML model was developed on the training set using fivefold stratified cross-validation. The test dataset was used to compare the performance of expert readers to the model. The primary endpoint was oCAD on invasive coronary angiography (ICA). Results: ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.94) for the training dataset and 0.89 (95% CI 0.84-0.93) for the test dataset. The ML model showed no significant differences as compared to the expert readers (p ≥ 0.03) in accuracy (89% vs. 88%), sensitivity (68% vs. 69%), and specificity (92% vs. 90%). Conclusion: The ML model resulted in a similar diagnostic performance as compared to expert readers, and may be deployed as a risk stratification tool for obstructive CAD. This study showed that utilization of ML is promising in the diagnosis of obstructive CAD. [ABSTRACT FROM AUTHOR]

Aims: In a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available. Methods and results: Echocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I‐II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP‐free survival at a median follow‐up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84–0.98). An abnormal LASr (<18%) was associated with a five‐fold increase in reaching the PEP. Conclusions: In HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real‐world Western European cohort. Methods: Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK‐HF registry. The CHECK‐HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2) was performed. Results: Seven thousand six hundred seventy‐one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2, and 618 (8.1%) had a BMI ≥35 kg/m2. Median BMI was 26.4 kg/m2. Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline‐directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline‐recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline‐recommended target dose of beta‐blockers (OR 1.34, 95% CI 1.10–1.62), renin–angiotensin system (RAS)‐inhibitors (OR 1.34, 95% CI 1.15–1.57) and MRAs (OR 1.40, 95% CI 1.04–1.87). Conclusions: Guideline‐recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelioid hemangioendothelioma (EHE) is a very rare malignant vascular neoplasm with unpredictable clinical course due to its remarkable heterogeneity. Large cohort studies with molecularly/immunohistochemically confirmed EHE are scarce, and what determines survival has been controversial. This retrospective nationwide cohort study addresses EHE epidemiology and aims to identify clinical and histopathological parameters with prognostic significance, thereby providing useful insights into the clinical behavior of this rare cancer. Our findings emphasize the aggressive behavior of EHE, demonstrated by lower 1- and 5-year overall survival rates compared to those in the current literature. Moreover, we confirmed the usefulness of the risk stratification model by Shibayama for unifocal disease and showed that multifocal and metastatic disease have no survival differences, indicating that multifocality is early metastatic disease. Tumors in the head and neck area have a higher propensity for lymph node metastases, entailing consideration of lymphadenectomy. Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study, we aimed to investigate prognostic factors based on clinicopathologic findings in a molecularly/immunohistochemically confirmed nationwide multicenter cohort of 57 EHE cases. Patients had unifocal disease (n = 29), multifocal disease (n = 5), lymph node metastasis (n = 8) and/or distant metastasis (n = 15) at the time of diagnosis. The overall survival rate was 71.4% at 1 year and 50.7% at 5 years. Survival did not correlate with sex, age or histopathological parameters. No survival differences were observed between multifocal and metastatic disease, suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al., dividing the cases into low- (n = 4), intermediate- (n = 15) and high- (n = 3) risk groups. No clinical or histopathological parameters were associated with progressive unifocal disease course. Lymph node metastases at the time of diagnosis occurred in 14.0% of the cases and were mainly associated with tumor localization in the head and neck area, proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previously described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis. [ABSTRACT FROM AUTHOR]

Climate directly influences the epidemiology of vector-borne diseases at various spatial and temporal scales. Following the recent increased incidences of theileriosis in Zimbabwe, a disease mainly transmitted by Rhipicephalus appendiculatus, we determined lethal temperatures for the species and current and possible future distribution using the machine learning algorithm 'Maxent'. Rhipicephalus appendiculatus larvae had an upper lethal temperature (ULT50) of about 44 ± 0.5 °C and this was marginally higher for nymphs and adults at 46 ± 0.5 °C. Environmental temperatures recorded in selected zonal tick microhabitats were below the determined lethal limits, indicating the ability of the tick to survive these regions. The resultant model under current climatic conditions showed areas with high suitability indices to the eastern, northeastern and southeastern parts of the country, mainly in Masvingo, Manicaland and Mashonaland Central provinces. Future predictions as determined by 2050 climatic conditions indicate a reduction in suitable habitats with the tick receding to presently cooler high elevation areas such as the eastern Highlands of Zimbabwe and a few isolated pockets in the interior of the country. Lowveld areas show low suitability under current climatic conditions and are expected to remain unsuitable in future. Overall, the study shows that R. appendiculatus distribution is constrained by climatic factors and helps identify areas of where occurrence of the species and the disease it transmits is highly likely. This will assist in optimizing disease surveillance and vector management strategies targeted at the species. [ABSTRACT FROM AUTHOR]

Background: Pre-test genetic counseling for patients with breast cancer is increasingly being provided by nongenetic healthcare professionals. We evaluated the attitudes, knowledge, and self-efficacy of surgeons, oncologists, and nurses regarding mainstream genetic testing and the feasibility to incorporate pre-test genetic counseling into routine care. Methods: We offered an online training to healthcare professionals from 13 hospitals and implemented a mainstream genetic testing pathway in 11/13 (85%) hospitals. Questionnaires were sent before (T0) and 6 months after (T1) completing the training. Those who did not complete the training received a questionnaire to assess their motivations. Results: In 11 hospitals, 80 (65%) healthcare professionals completed the training, of whom 70 (88%) completed both questionnaires. The attitudes, (perceived) knowledge and self-efficacy of healthcare professionals were high both at baseline and 6 months after completing the training. After 6 months, their perceived knowledge about the advantages and disadvantages of a genetic test and implications for family members had significantly improved (p = 0.012 and p = 0.021, respectively). For the majority (89%), the time investment for pre-test genetic counseling was less than 15 min per patient and as expected or better. Healthcare professionals considered the total time investment feasible to incorporate mainstream genetic testing into their daily practice. The main barrier to complete the training was lack of time. The online training was considered useful, with a rating of 8/10. Conclusion: Surgical oncologists and nurses in breast cancer care feel well-equipped and motivated to provide pre-test genetic counseling after completion of an online training module. [ABSTRACT FROM AUTHOR]

Heatwaves affect tidal flat ecosystems by altering the bioturbating behavior of benthic species, with potential consequences for sediment oxygenation, particle mixing, and erodibility. Although the frequency and duration of heatwaves are expected to increase under global warming scenarios, we lack insights into how heatwaves' temporal dynamics affect bioturbating behaviors. Using the widely distributed bioturbator Cerastoderma edule as model species, we quantified how heatwaves with identical heat‐sum but different temporal dynamics (i.e., 3‐ vs. 6‐d heating and normal temperature cycles) affect bioturbating behaviors and the sediment mixing processes in tidal mesocosms. Our results show that short but frequent 3‐d heatwave cycles increased the magnitude of bioturbating behaviors, thereby resulting in more bio‐mixed sediment than observed under infrequent prolonged 6‐d heatwave cycles. This unexpected result could be ascribed to the weakening health condition indicated by a high death rate (47.37%) under 6‐d heatwave cycles than in 3‐d and no‐heatwave control cycles. Present findings reveal that the impact of heatwaves on sediment bioturbation will strongly depend on the temporal dynamics of future heatwaves: bioturbation will be enhanced unless the heatwave duration exceeds species resistance and increases mortality. [ABSTRACT FROM AUTHOR]

We hypothesize that a novel tailor-made cardiac rehabilitation (CR) program for obesity patients (OPTICARE XL) has better outcomes as compared to usual CR regarding parameters of cardiac function as measured by conventional and advanced transthoracic echocardiography. This is an open-label, randomized controlled trial. Inclusion criteria were: patients referred to CR with a body mass index (BMI) ≥30 kg/m2, and age ≥18 years with either coronary artery disease or nonvalvular atrial fibrillation. The experimental group participated in OPTICARE XL and the controls received the usual CR. Subjects randomized to OPTICARE XL received on top of usual CR behavioural therapy for a healthy diet and an active lifestyle for the first 12 weeks. Also, the exercise program was more tailored. Furthermore, a behavioural after-care program was organized with 6 meetings between weeks 13-52. Transthoracic (speckle tracking) echocardiography was performed at baseline and one-year follow-up. A total of 42 patients completed the follow-up, 21 in both groups. There was a mild but statistically significant reduction in weight over time, however, this was comparable between groups. There was no improvement observed in any of the echocardiographic parameters. In conclusion, cardiac function in obesity patients was not improved one-year after a novel tailor-made CR program (OPTICARE XL) as compared to usual CR. [ABSTRACT FROM AUTHOR]

Background: The Coronavirus Disease 2019 (COVID-19) pandemic and associated mitigation policies created a global economic and health crisis of unprecedented depth and scale, raising the estimated prevalence of depression by more than a quarter in high-income countries. Low- and middle-income countries (LMICs) suffered the negative effects on living standards the most severely. However, the consequences of the pandemic for mental health in LMICs have received less attention. Therefore, this study assesses the association between the COVID-19 crisis and mental health in 8 LMICs. Methods and findings: We conducted a prospective cohort study to examine the correlation between the COVID-19 pandemic and mental health in 10 populations from 8 LMICs in Asia, Africa, and South America. The analysis included 21,162 individuals (mean age 38.01 years, 64% female) who were interviewed at least once pre- as well as post-pandemic. The total number of survey waves ranged from 2 to 17 (mean 7.1). Our individual-level primary outcome measure was based on validated screening tools for depression and a weighted index of depression questions, dependent on the sample. Sample-specific estimates and 95% confidence intervals (CIs) for the association between COVID-19 periods and mental health were estimated using linear regressions with individual fixed effects, controlling for independent time trends and seasonal variation in mental health where possible. In addition, a regression discontinuity design was used for the samples with multiple surveys conducted just before and after the onset of the pandemic. We aggregated sample-specific coefficients using a random-effects model, distinguishing between estimates for the short (0 to 4 months) and longer term (4+ months). The random-effects aggregation showed that depression symptoms are associated with a increase by 0.29 standard deviations (SDs) (95% CI [−.47, −.11], p-value = 0.002) in the 4 months following the onset of the pandemic. This change was equivalent to moving from the 50th to the 63rd percentile in our median sample. Although aggregate depression is correlated with a decline to 0.21 SD (95% CI [−0.07, −.34], p-value = 0.003) in the period thereafter, the average recovery of 0.07 SD (95% CI [−0.09,.22], p-value = 0.41) was not statistically significant. The observed trends were consistent across countries and robust to alternative specifications. Two limitations of our study are that not all samples are representative of the national population, and the mental health measures differ across samples. Conclusions: Controlling for seasonality, we documented a large, significant, negative association of the pandemic on mental health, especially during the early months of lockdown. The magnitude is comparable (but opposite) to the effects of cash transfers and multifaceted antipoverty programs on mental health in LMICs. Absent policy interventions, the pandemic could be associated with a lasting legacy of depression, particularly in settings with limited mental health support services, such as in many LMICs. We also demonstrated that mental health fluctuates with agricultural crop cycles, deteriorating during "lean", pre-harvest periods and recovering thereafter. Ignoring such seasonal variations in mental health may lead to unreliable inferences about the association between the pandemic and mental health. Nursena Aksunger and colleagues investigate the association between the COVID-19 pandemic and mental health in eight low- and middle-income countries. Author summary: Why was this study done?: The worldwide economic and health crises triggered by the Coronavirus Disease 2019 (COVID-19) pandemic have had a significant influence on mental health, with the estimated prevalence of depression having increased by more than 25% in high-income countries. Although the adverse consequences of the pandemic on living standards have been most severe in low- and middle-income countries (LMICs), the consequences of the pandemic for mental health in LMICs have received less attention. What did the researchers do and find?: The purpose of this research is to investigate the association between the COVID-19 pandemic and mental health in 8 LMICs in Asia, Africa, and South America. Before and during the pandemic, the mental health of 21,162 individuals (mean age 38.01 years, 64.0% female) was measured using survey data. Our individual-level primary outcome measure was based on validated depression screening instruments and a sample-specific weighted index of depression questions. We found that depression symptoms were associated with a significant increase in the 4 months following the onset of the pandemic (0.29 standard deviations (SDs), 95% confidence interval (CI) [−.47, −.11], p-value = 0.002) and that the average recovery of 0.07 SD was not statistically significant in the subsequent period (95% CI [−0.09,.22], p-value = 0.41). What do these findings mean?: We showed a substantial negative correlation between the COVID-19 pandemic and mental health after adjusting for seasonality, suggesting that the pandemic might induce long-term depression, especially in LMICs with poor mental health support facilities. We also provided evidence for seasonal changes in mental health depending on agricultural crop cycle. This seasonality should be considered when examining changes in mental health over time in order to prevent drawing inaccurate conclusions. The observed trends were consistent across countries and robust to alternative analyses, although the study was limited by the fact that not all samples were representative of the national population and the mental health indicators differed among samples. [ABSTRACT FROM AUTHOR]