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Long-term analyses of biodiversity data highlight a 'biodiversity conservation paradox': biological communities show substantial species turnover over the past century1,2, but changes in species richness are marginal1,3-5. Most studies, however, have focused only on the incidence of species, and have not considered changes in local abundance. Here we asked whether analysing changes in the cover of plant species could reveal previously unrecognized patterns of biodiversity change and provide insights into the underlying mechanisms. We compiled and analysed a dataset of 7,738 permanent and semi-permanent vegetation plots from Germany that were surveyed between 2 and 54 times from 1927 to 2020, in total comprising 1,794 species of vascular plants. We found that decrements in cover, averaged across all species and plots, occurred more often than increments; that the number of species that decreased in cover was higher than the number of species that increased; and that decrements were more equally distributed among losers than were gains among winners. Null model simulations confirmed that these trends do not emerge by chance, but are the consequence of species-specific negative effects of environmental changes. In the long run, these trends might result in substantial losses of species at both local and regional scales. Summarizing the changes by decade shows that the inequality in the mean change in species cover of losers and winners diverged as early as the 1960s. We conclude that changes in species cover in communities represent an important but understudied dimension of biodiversity change that should more routinely be considered in time-series analyses.

The neurological severity of a spinal cord injury (SCI) is commonly classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS). The aim of this study was to assess the course of the AIS following SCI, and to discern the nature of any changes in the classification that occur. Assessments were performed in a European cohort of SCI patients within 2 weeks and at 1, 3, 6, and 12 months after the initial injury. Overall, about 70% of the patients initially diagnosed as AIS A did not convert, as did 90% of the AIS D patients. When only evaluating patients with complete datasets, 68% did not convert, while the AIS category improved in 30% of patients and deteriorated in 2%. A change in the last sacral segments (40%), motor improvement (31%), sensory improvement (19%), and a change in the neurological level of the SCI (10%) contributed to or accompanied the AIS conversion. When the AIS remained unchanged between successive assessment points, there was no change in the number of muscles graded three or more (NMG3(+)) in 73% of the transitions. An improvement in AIS was associated with a gain in NMG3(+) in 49% of the transitions, while an aggravation in AIS was accompanied by a loss in NMG3(+) in 10% of the transitions. These results, documenting a substantial amount of spontaneous AIS conversions, should be taken into consideration when designing clinical trials to assess the effects of potential new treatments for SCI.

The neurological severity of a spinal cord injury (SCI) is commonly classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS). The aim of this study was to assess the course of the AIS following SCI, and to discern the nature of any changes in the classification that occur. Assessments were performed in a European cohort of SCI patients within 2 weeks and at 1, 3, 6, and 12 months after the initial injury. Overall, about 70% of the patients initially diagnosed as AIS A did not convert, as did 90% of the AIS D patients. When only evaluating patients with complete datasets, 68% did not convert, while the AIS category improved in 30% of patients and deteriorated in 2%. A change in the last sacral segments (40%), motor improvement (31%), sensory improvement (19%), and a change in the neurological level of the SCI (10%) contributed to or accompanied the AIS conversion. When the AIS remained unchanged between successive assessment points, there was no change in the number of muscles graded three or more (NMG3(+)) in 73% of the transitions. An improvement in AIS was associated with a gain in NMG3(+) in 49% of the transitions, while an aggravation in AIS was accompanied by a loss in NMG3(+) in 10% of the transitions. These results, documenting a substantial amount of spontaneous AIS conversions, should be taken into consideration when designing clinical trials to assess the effects of potential new treatments for SCI.

Background: Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. Methods: Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). Results: Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P=0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P<0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P=0.030). Conclusion: Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival. Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.

Homologous recombination is essential for the accurate repair of double-stranded DNA breaks (DSBs)1. Initially, the RecBCD complex2 resects the ends of the DSB into 3′ single-stranded DNA on which a RecA filament assembles3. Next, the filament locates the homologous repair template on the sister chromosome4. Here we directly visualize the repair of DSBs in single cells, using high-throughput microfluidics and fluorescence microscopy. We find that, in Escherichia coli, repair of DSBs between segregated sister loci is completed in 15 ± 5 min (mean ± s.d.) with minimal fitness loss. We further show that the search takes less than 9 ± 3 min (mean ± s.d) and is mediated by a thin, highly dynamic RecA filament that stretches throughout the cell. We propose that the architecture of the RecA filament effectively reduces search dimensionality. This model predicts a search time that is consistent with our measurement and is corroborated by the observation that the search time does not depend on the length of the cell or the amount of DNA. Given the abundance of RecA homologues5, we believe this model to be widely conserved across living organisms., QC 20220502Erratum Correction Corrigendum in DOI: 10.1038/s41586-021-04154-2

Mortality rates for coronary heart disease (CHD) experience a longstanding decline, attributed to progress in prevention, diagnostics and therapy. However, CHD mortality rates vary between countries. To estimate whether national patterns of causes of death impact CHD mortality, data from the WHO “European detailed mortality database” for 2000 and 2013 for populations aged ≥ 80 years was analyzed. We extracted mortality rates for total mortality, cardiovascular diseases, neoplasms, dementia and ill-defined causes. We calculated proportions of selected causes of death among all deaths, and proportions of selected cardiovascular causes among cardiovascular deaths. CHD mortality rates were recalculated after re-coding ill-defined causes of death. Association between CHD mortality rates and proportions of CHD deaths was estimated by population-weighted linear regression. National patterns of causes of death were divers. In 2000, CHD was assigned as cause of death in 13–53% of all cardiovascular deaths. Until 2013, this proportion changed between − 65% (Czech Republic) and + 57% (Georgia). Dementia was increasingly assigned as underlying cause of death in Western Europe, but rarely in eastern European countries. Ill-defined causes accounted for between < 1% and 53% of all cardiovascular deaths. CHD mortality rates were closely linked to a countries’ proportion of cardiovascular deaths assigned to CHD (R2 = 0.95 for 2000 and 0.99 for 2013). We show that CHD mortality is considerably influenced by national particularities in certifying death. Changes in CHD mortality rates reflect changes in certifying competing underlying causes of death. This must be accounted for when discussing reasons for the CHD mortality decline. © 2020, The Author(s).

Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses. This early Miocene (∼16 million years ago [mya]) split post-dates the land bridge formation between the Afro-Arabian and Eurasian landmasses. Our analyses also show that while rhinoceros genomes in general exhibit low levels of genome-wide diversity, heterozygosity is lowest and inbreeding is highest in the modern species. These results suggest that while low genetic diversity is a long-term feature of the family, it has been particularly exacerbated recently, likely reflecting recent anthropogenic-driven population declines. © 2021 The Authors.

What have been the causes and consequences of technological evolution in world history? In particular, what propels innovation and diffusion of military technologies, details of which are comparatively well preserved and which are often seen as drivers of broad socio-cultural processes? Here we analyze the evolution of key military technologies in a sample of pre-industrial societies world-wide covering almost 10,000 years of history using Seshat: Global History Databank. We empirically test previously speculative theories that proposed world population size, connectivity between geographical areas of innovation and adoption, and critical enabling technological advances, such as iron metallurgy and horse riding, as central drivers of military technological evolution. We find that all of these factors are strong predictors of change in military technology, whereas state-level factors such as polity population, territorial size, or governance sophistication play no major role. We discuss how our approach can be extended to explore technological change more generally, and how our results carry important ramifications for understanding major drivers of evolution of social complexity. © 2021 Turchin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

This study reports the immobilization of two biocatalysts (e.g., cytochrome c—Cyt c—and the non-metalloenzyme formate dehydrogenase from Candida boidinii–cbFDH) on a series of mesoporous carbons with controlled pore sizes. The catalytic activity of the nanoconfined proteins was correlated with the pore size distribution of the carbon materials used as supports. The electrochemical behaviour of nanoconfined Cyt c showed direct electron transfer electroactivity in pore sizes matching tightly the protein dimension. The pseudo-peroxidase activity towards H2O2 reduction was enhanced at pH 4.0, due to the protein conformational changes. For cbFDH, the reduction of CO2 towards formic acid was evaluated for the nanoconfined protein, in the presence of nicotinamide adenine dinucleotide (NADH). The carbons displayed different cbFDH uptake capacity, governed by the dimensions of the main mesopore cavities and their accessibility through narrow pore necks. The catalytic activity of nanoconfined cbFDH was largely improved, compared to its performance in free solution. Regardless of the carbon support used, the production of formic acid was higher upon immobilization with lower nominal cbFDH:NADH ratios., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

Background: Despite emerging evidence of a delay of migration to older ages, few studies have considered its impact on overall migration levels. Objective: This paper argues that there are two possible implications of delayed migration on overall migration levels: (1) a tempo effect leading to a temporary underestimation of the level of migration in the observed period data and (2) a migration ageing effect leading to a reduction of higher-order moves because the exposure to migration is shifted to older ages when the probability of moving is lower. Methods: Combining hypothetical scenarios with empirical evidence from a range of countries in Europe, North America, Australia, and China, the paper demonstrates the relevance of tempo and ageing effects to migration analysis and proposes a framework for conceptualising these processes. Results: Our analysis suggests that both tempo and ageing effects are likely to occur if the general trend is towards later ages at migration. We show, however, that all-move data such as those collected in censuses is not suitable to analyse tempo effects because changes in migration behaviour are order specific. Drawing on retrospective survey data, we show that in 25 of 26 European countries considered in this paper, individuals who are late in leaving the parental home are less likely to progress to the second move and, as a result, report a lower number of migrations in adulthood than early movers. Contribution: The results underline the need to collect and analyse migration data by move order to understand migration trends while highlighting the paucity of such data.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a serious form of stroke, for which rapid access to specialist neurocritical care is associated with better outcomes. Delays in the treatment of aSAH appear to be common and may contribute to poor outcomes. We have a limited understanding of the extent and causes of these delays, which hinders the development of interventions to reduce delays and improve outcomes. The aim of this systematic review was to quantify and identify factors associated with time to treatment in aSAH. METHOD(S): This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines and was registered in PROSPERO (Reg. No. CRD42019132748). We searched four electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) for manuscripts published from January 1998 using pre-designated search terms and search strategy. Main outcomes were duration of delays of time intervals from onset of aSAH to definitive treatment and/or factors related to time to treatment. RESULT(S): A total of 64 studies with 16 different time intervals in the pathway of aSAH patients were identified. Measures of time to treatment varied between studies (e.g. cut-off timepoints or absolute mean/median duration). Factors associated with time to treatment fell into two categories-individual (n=9 factors, e.g. age, sex and clinical characteristics) and health system (n=8 factors, e.g. pre-hospital delay or presentation out-of-hours). Demographic factors were not associated with time to treatment. More severe aSAH reduced treatment delay in most studies. Pre-hospital delays (patients delay, late referral, late arrival of ambulance, being transferred between hospitals or arriving at the hospital outside of office hours) were associated with treatment delay. In-hospital factors (patients with complications, procedure before definitive treatment, slow work-up and type of treatment) were less associated wi

STUDY QUESTION: Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women? SUMMARY ANSWER: Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12months on the probability of conception leading to live birth in women of different age groups with different categories of infertility. WHAT IS KNOWN ALREADY: Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility. STUDY DESIGN, SIZE, DURATION: A population-based cohort study based on national data from all licensed clinics in the UK obtained from the Human Fertilisation and Embryology Authority Register. Linked data from 9589 women who underwent their first IVF or ICSI treatment in 2017 and consented to the use of their data for research were used to predict livebirth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were used to estimate the chances of livebirth associated with immediate treatment versus a delay of 6 and 12months in couples about to embark on IVF or ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: We estimated that a 6-month delay would reduce IVF livebirths by 0.4%, 2.4%, 5.6%, 9.5% and 11.8% in women aged <30, 30-35, 36-37, 38-39 and 40-42years, respectively, while corresponding values associated with a delay of 12months were 0.9%, 4.9%, 11.9%, 18.8% and 22.4%, respectively. In women with known causes of infertility, worst case (best case) predicted chances of livebirth after a delay of 6months followed by one complete IVF cycle in women aged <30, 30-35, 36-37, 38-39 and 4

The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a serious form of stroke, for which rapid access to specialist neurocritical care is associated with better outcomes. Delays in the treatment of aSAH appear to be common and may contribute to poor outcomes. We have a limited understanding of the extent and causes of these delays, which hinders the development of interventions to reduce delays and improve outcomes. The aim of this systematic review was to quantify and identify factors associated with time to treatment in aSAH. METHOD(S): This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines and was registered in PROSPERO (Reg. No. CRD42019132748). We searched four electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) for manuscripts published from January 1998 using pre-designated search terms and search strategy. Main outcomes were duration of delays of time intervals from onset of aSAH to definitive treatment and/or factors related to time to treatment. RESULT(S): A total of 64 studies with 16 different time intervals in the pathway of aSAH patients were identified. Measures of time to treatment varied between studies (e.g. cut-off timepoints or absolute mean/median duration). Factors associated with time to treatment fell into two categories-individual (n=9 factors, e.g. age, sex and clinical characteristics) and health system (n=8 factors, e.g. pre-hospital delay or presentation out-of-hours). Demographic factors were not associated with time to treatment. More severe aSAH reduced treatment delay in most studies. Pre-hospital delays (patients delay, late referral, late arrival of ambulance, being transferred between hospitals or arriving at the hospital outside of office hours) were associated with treatment delay. In-hospital factors (patients with complications, procedure before definitive treatment, slow work-up and type of treatment) were less associated wi

STUDY QUESTION: Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women? SUMMARY ANSWER: Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12months on the probability of conception leading to live birth in women of different age groups with different categories of infertility. WHAT IS KNOWN ALREADY: Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility. STUDY DESIGN, SIZE, DURATION: A population-based cohort study based on national data from all licensed clinics in the UK obtained from the Human Fertilisation and Embryology Authority Register. Linked data from 9589 women who underwent their first IVF or ICSI treatment in 2017 and consented to the use of their data for research were used to predict livebirth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were used to estimate the chances of livebirth associated with immediate treatment versus a delay of 6 and 12months in couples about to embark on IVF or ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: We estimated that a 6-month delay would reduce IVF livebirths by 0.4%, 2.4%, 5.6%, 9.5% and 11.8% in women aged <30, 30-35, 36-37, 38-39 and 40-42years, respectively, while corresponding values associated with a delay of 12months were 0.9%, 4.9%, 11.9%, 18.8% and 22.4%, respectively. In women with known causes of infertility, worst case (best case) predicted chances of livebirth after a delay of 6months followed by one complete IVF cycle in women aged <30, 30-35, 36-37, 38-39 and 4

The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification8,9 or oxygen may increase as a result of enhanced primary production10. Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world’s oceans6,7 and could threaten essential lake ecosystem services2,3,5,11.

Background: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. Methods: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. Findings: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be r

BACKGROUND: Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS: A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS: We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4–13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged <6 years, and, in particular, those aged <3 years, developed higher long-lasting levels of nAbs compared with older siblings and/or adults. CONCLUSIONS: Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.

Modeling real-life transportation problems usually require the simultaneous incorporation of different variants of the classical vehicle routing problem (VRP). The periodic VRP (PVRP) is a classical extension in which routes are determined for a planning period of several days and each customer has an associated set of allowable visit schedules. This work proposes a unified model framework for PVRP that consists of multiple attributes or variants not previously addressed simultaneously, such as time-windows, time-dependence, and consistency-which guarantees the visits to customer by the same vehicle-, together with three objective functions that respond to the needs of practical problems. The numerical experimentation is focused on the effects of three factors: frequency, depot centrality, and the objective function on the performance of a general-purpose MILP solver, through the analysis of the achieved relative gaps. Results show higher sensitivity to the objective functions and to the problem sizes. © 2020 Baldoquin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Objective The viscoelastic behavior of dentin and its ability to undergo time dependent deformation are considered to be important to oral functions and its capacity to resist fracture. There are spatial variations in the microstructure of dentin within the crown, which could be important to the viscous behavior. However, a spatially resolved description for the viscoelastic behavior of coronal dentin has not been reported. Methods In this investigation spherical indentations were made in three regions of coronal dentin including the outer, middle and inner regions. Power law relations were developed to quantitatively describe the stress-strain responses of the tissue. Results Results showed that the deformation behavior was strongly dependent on the composition (mineral to collagen ratio) and microstructure (tubule density), which contributed to an increase in the rate of viscous deformation with increasing proximity to the pulp. Conclusions A model accounting for spatial variations in composition and microstructure was developed to describe the steady-state time dependent deformation behavior of coronal dentin, and a good agreement was found with the experimental results. © 2017 Elsevier Ltd

Background: Media frequently report on overall work-place challenges in Swedish schools, including teachers’ working conditions, their well-being, and students’ declining results. Language is the key to success in every school subject. Therefore, optimal language learning environments are important. Poor sound environments affect teachers’ vocal health, their general well-being, and students’ performance. To provide better conditions for teachers and students, it is necessary to combine optimized room acoustics with other preventive measures such as vocal training and evidence-based tools to improve classroom communication. Teachers play a key role in the classroom and need knowledge and skills in communicative strategies to ensure first-class communication. The purpose of this study is to explore the effects of an intervention program for primary-school teachers comprising strategies for enhanced language learning and interactions in the classroom, with focus on teachers’ verbal and body communication (voice, gaze, and gesture). Methods: Teachers (n = 25) from seven schools teaching in school year 3–6 participated. Assessments were made pre/post intervention and at 5-weeks and 3-months follow-up. The assessments included teachers’ self-assessments (questionnaires) of vocal health, self-efficacy, stress, burnout, and psychosocial work-environment. Results: The main results were significant decrease in voice problems at the 3-months follow-up and significant decrease of both stress and degree of burnout at 5-weeks follow-up. Self-efficacy score had increased significantly at 5-week follow-up. Conclusion: It can be concluded that the intervention program improves teachers’ self-reported vocal health, decreases their perception of stress, and degree of burnout whilst increasing their sense of self-efficacy in classroom management.

Background: Media frequently report on overall work-place challenges in Swedish schools, including teachers’ working conditions, their well-being, and students’ declining results. Language is the key to success in every school subject. Therefore, optimal language learning environments are important. Poor sound environments affect teachers’ vocal health, their general well-being, and students’ performance. To provide better conditions for teachers and students, it is necessary to combine optimized room acoustics with other preventive measures such as vocal training and evidence-based tools to improve classroom communication. Teachers play a key role in the classroom and need knowledge and skills in communicative strategies to ensure first-class communication. The purpose of this study is to explore the effects of an intervention program for primary-school teachers comprising strategies for enhanced language learning and interactions in the classroom, with focus on teachers’ verbal and body communication (voice, gaze, and gesture). Methods: Teachers (n = 25) from seven schools teaching in school year 3–6 participated. Assessments were made pre/post intervention and at 5-weeks and 3-months follow-up. The assessments included teachers’ self-assessments (questionnaires) of vocal health, self-efficacy, stress, burnout, and psychosocial work-environment. Results: The main results were significant decrease in voice problems at the 3-months follow-up and significant decrease of both stress and degree of burnout at 5-weeks follow-up. Self-efficacy score had increased significantly at 5-week follow-up. Conclusion: It can be concluded that the intervention program improves teachers’ self-reported vocal health, decreases their perception of stress, and degree of burnout whilst increasing their sense of self-efficacy in classroom management.

Background: Media frequently report on overall work-place challenges in Swedish schools, including teachers’ working conditions, their well-being, and students’ declining results. Language is the key to success in every school subject. Therefore, optimal language learning environments are important. Poor sound environments affect teachers’ vocal health, their general well-being, and students’ performance. To provide better conditions for teachers and students, it is necessary to combine optimized room acoustics with other preventive measures such as vocal training and evidence-based tools to improve classroom communication. Teachers play a key role in the classroom and need knowledge and skills in communicative strategies to ensure first-class communication. The purpose of this study is to explore the effects of an intervention program for primary-school teachers comprising strategies for enhanced language learning and interactions in the classroom, with focus on teachers’ verbal and body communication (voice, gaze, and gesture). Methods: Teachers (n = 25) from seven schools teaching in school year 3–6 participated. Assessments were made pre/post intervention and at 5-weeks and 3-months follow-up. The assessments included teachers’ self-assessments (questionnaires) of vocal health, self-efficacy, stress, burnout, and psychosocial work-environment. Results: The main results were significant decrease in voice problems at the 3-months follow-up and significant decrease of both stress and degree of burnout at 5-weeks follow-up. Self-efficacy score had increased significantly at 5-week follow-up. Conclusion: It can be concluded that the intervention program improves teachers’ self-reported vocal health, decreases their perception of stress, and degree of burnout whilst increasing their sense of self-efficacy in classroom management.

Background: Media frequently report on overall work-place challenges in Swedish schools, including teachers’ working conditions, their well-being, and students’ declining results. Language is the key to success in every school subject. Therefore, optimal language learning environments are important. Poor sound environments affect teachers’ vocal health, their general well-being, and students’ performance. To provide better conditions for teachers and students, it is necessary to combine optimized room acoustics with other preventive measures such as vocal training and evidence-based tools to improve classroom communication. Teachers play a key role in the classroom and need knowledge and skills in communicative strategies to ensure first-class communication. The purpose of this study is to explore the effects of an intervention program for primary-school teachers comprising strategies for enhanced language learning and interactions in the classroom, with focus on teachers’ verbal and body communication (voice, gaze, and gesture). Methods: Teachers (n = 25) from seven schools teaching in school year 3–6 participated. Assessments were made pre/post intervention and at 5-weeks and 3-months follow-up. The assessments included teachers’ self-assessments (questionnaires) of vocal health, self-efficacy, stress, burnout, and psychosocial work-environment. Results: The main results were significant decrease in voice problems at the 3-months follow-up and significant decrease of both stress and degree of burnout at 5-weeks follow-up. Self-efficacy score had increased significantly at 5-week follow-up. Conclusion: It can be concluded that the intervention program improves teachers’ self-reported vocal health, decreases their perception of stress, and degree of burnout whilst increasing their sense of self-efficacy in classroom management.

Main conclusion: Swelling of sweet cherry cell walls is a physical process counterbalanced by turgor. Cell turgor prevents swelling in intact cells, whereas loss of turgor allows cell walls to swell. Abstract: Swelling of epidermal cell walls precedes skin failure in sweet cherry (Prunus avium) cracking. Swollen cell walls lead to diminished cell:cell adhesions. We identify the mechanism of cell wall swelling. Swelling was quantified microscopically on epidermal sections following freeze/thaw treatment or by determining swelling pressure or swelling capacity of cell wall extracts. Releasing turgor by a freeze/thaw treatment increased cell wall thickness 1.6-fold within 2 h. Pressurizing cell wall extracts at > 12 kPa prevented swelling in water, while releasing the pressure increased swelling. The effect was fully reversible. Across cultivars, cell wall thickness before and after turgor release in two subsequent seasons was significantly correlated (before release of turgor: r = 0.71**, n = 14; after release of turgor: r = 0.73**, n = 14) as was the swelling of cell walls upon turgor release (r = 0.71**, n = 14). Close relationships were also identified for cell wall thickness of fruit of the same cultivars grown in the greenhouse and the field (before release of turgor: r = 0.60, n = 10; after release of turgor: r = 0.78**, n = 10). Release of turgor by heating, plasmolysis, incubation in solvents or surfactants resulted in similar swelling (range 2.0–3.1 µm). Cell wall swelling increased from 1.4 to 3.0 µm as pH increased from pH 2.0 to 5.0 but remained nearly constant between pH 5.0 and 8.0. Increasing ethanol concentration decreased swelling. Swelling of sweet cherry cell walls is a physical process counterbalanced by turgor. © 2020, The Author(s).

Background: Media frequently report on overall work-place challenges in Swedish schools, including teachers’ working conditions, their well-being, and students’ declining results. Language is the key to success in every school subject. Therefore, optimal language learning environments are important. Poor sound environments affect teachers’ vocal health, their general well-being, and students’ performance. To provide better conditions for teachers and students, it is necessary to combine optimized room acoustics with other preventive measures such as vocal training and evidence-based tools to improve classroom communication. Teachers play a key role in the classroom and need knowledge and skills in communicative strategies to ensure first-class communication. The purpose of this study is to explore the effects of an intervention program for primary-school teachers comprising strategies for enhanced language learning and interactions in the classroom, with focus on teachers’ verbal and body communication (voice, gaze, and gesture). Methods: Teachers (n = 25) from seven schools teaching in school year 3–6 participated. Assessments were made pre/post intervention and at 5-weeks and 3-months follow-up. The assessments included teachers’ self-assessments (questionnaires) of vocal health, self-efficacy, stress, burnout, and psychosocial work-environment. Results: The main results were significant decrease in voice problems at the 3-months follow-up and significant decrease of both stress and degree of burnout at 5-weeks follow-up. Self-efficacy score had increased significantly at 5-week follow-up. Conclusion: It can be concluded that the intervention program improves teachers’ self-reported vocal health, decreases their perception of stress, and degree of burnout whilst increasing their sense of self-efficacy in classroom management.

BACKGROUND: Cardiac magnetic resonance (CMR) is the standard of reference for myocardial fibrosis detection by late gadolinium enhancement. Cardiac computed tomography (CCT) is emerging as a promising alternative. The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the feasibility and diagnostic accuracy of a comprehensive functional and anatomical cardiac evaluation with CCT as compared with CMR and invasive coronary angiography as standard of reference. METHODS: Consecutive patients with a newly diagnosed left ventricle (LV) dysfunction (left ventricular ejection fraction <50%) and a clinical indication to CMR will be screened. Exclusion criteria will be contraindications to contrast agents and impaired renal function. CCT will be performed per protocol within 10 days from CMR. A total of 100 patients will be enrolled within 24 months. We will evaluate with CCT volume and ejection fraction of the LV and right ventricle, presence, extent and pattern of delayed enhancement and cardiac venous system. Moreover, presence and degree of coronary stenoses will be evaluated among patients undergoing invasive coronary angiography in the 6 months following CCT. RESULTS: The primary study endpoints will be: first, to assess the diagnostic performance of CCT vs. CMR to detect the delayed enhancement in a territory-based and patient-based analysis; second, to assess the agreement between CCT and CMR in the discrimination between ischemic vs. nonischemic delayed enhancement patters in a territory-based analysis; third, to assess the correlation between CCT and CMR for LV and right ventricle end-diastolic and end-systolic volumes and ejection fraction measurements. CONCLUSION: The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the diagnostic performance of CCT using the latest

In contemporary global capitalist culture, time-consciousness becomes more important than self-consciousness. In the realm of lived time, the identity of the self opens up to an encounter with otherness. Insights into the ways in which this dynamic unfolds enable one to affirm human temporalities in their potential difference to the temporalities of global capitalism. The book offers an empirical exploration of lived temporalities on markets, in buses and in traditional subsistence in Guatemala, and a theoretical exploration of these through the philosophy of Gilles Deleuze and inter-relational approaches within psychoanalysis.

BACKGROUND: This study describes the temporal changes in risk profiles and outcomes among patients with aortic stenosis (AS) undergoing surgical aortic valve replacement (SAVR) in Australia between 2002 and 2015. METHOD(S): Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database, we identified first-recorded SAVR for AS over 14 years. Patients' surgical risk profiles, procedures, 30-day and 12-month outcomes were summarized before and after the introduction of transcatheter aortic valve implantation in Australia, in 2008. We applied multivariable regression models to investigate the changes over time on risk-adjusted 30-day mortality, re-hospitalization and 12-month mortality. RESULT(S): We identify a total of 18147 patients with AS who underwent SAVR; mostly men (64%) with a mean age of 72years. The proportion of major cardiac surgeries devoted to SAVR increased from 14% in 2002 to 20% in 2015. More SAVRs were performed electively (80% in 2002 versus 86% in 2015), and the recipients were at lower surgical risk (mean multi-risk score 3.9% in 2002 versus 3.0% in 2015). The use of bioprosthetic aortic valves increased over time (67% in 2002 to 88% in 2015). We found no significant changes in 30-day mortality, a significant decrease in 30-day readmission and minor fluctuations in 12-month mortality over the study period. CONCLUSION(S): SAVR comprises an increasingly larger proportion of all adult cardiac surgeries in Australia. There has been a greater use of bioprosthetic aortic valves, a fall in 30-day readmission but no significant changes in mortality.Copyright © 2019 Royal Australasian College of Surgeons.

OBJECTIVE: To identify discharge medications, especially psychotropic medications that are associated with falls, amongst older adults within 6 months following hospitalisation. METHOD(S): Negative binomial regression was used to examine relationships between discharge medications and falls in older post-hospitalised adults. Multiple regression that considered falls risk factors at discharge was performed. RESULT(S): Data for 267 participants showed that discharge medications were not independently associated with falls postdischarge after adjustment for other falls risk factors. Male gender (adjusted incidence rate ratio [95% confidence interval, CI]) 2.15 [1.36-3.40]), higher depression scores (1.14 [1.05-1.25]) and co-morbidity of neurological disease other than stroke (5.98 [3.08-11.60]) were independently associated with an increased rate of falls. Higher depression scores (1.20 [1.11-1.31]) and co-morbidity of cancer (1.97 [1.20-3.25]) were independently associated with an increased rate of injurious falls in the 6 months postdischarge. CONCLUSION(S): Falls prevention strategies, other than hospital discharge medication management in the postdischarge older adults, warrant investigation.Copyright © 2019 AJA Inc.

High-throughput and rapid serology assays to detect the antibody response specific to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in human blood samples are urgently required to improve our understanding of the effects of COVID-19 across the world. Short-term applications include rapid case identification and contact tracing to limit viral spread, while population screening to determine the extent of viral infection across communities is a longer-term need. Assays developed to address these needs should match the ASSURED criteria. We have identified agglutination tests based on the commonly employed blood typing methods as a viable option. These blood typing tests are employed in hospitals worldwide, are high-throughput, fast (10-30 min), and automated in most cases. Herein, we describe the application of agglutination assays to SARS-CoV-2 serology testing by combining column agglutination testing with peptide-antibody bioconjugates, which facilitate red cell cross-linking only in the presence of plasma containing antibodies against SARS-CoV-2. This simple, rapid, and easily scalable approach has immediate application in SARS-CoV-2 serological testing and is a useful platform for assay development beyond the COVID-19 pandemic.

BACKGROUND: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia. METHOD(S): We retrospectively reviewed data from all patients aged >=80 years who underwent curative-intent resection for NSCLC over 12years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival. RESULT(S): Two hundred patients aged >=80 years underwent curative-intent resections. Mortality at 30 and 120days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those >=83years, at 30days (6.8% versus 0.8%, P = 0.044) and 120days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients >=83years requiring lobectomy, compared to sub-lobar resection at 120days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02). CONCLUSION(S): In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.Copyright © 2018 Royal Australasian College of Surgeons.

Background: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. Method(s): A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. Result(s): There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. Conclusion(s): We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.Copyright © 2020 The Author(s).

AIM: Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. We aimed to study the effect of the Sepsis Pathway Programme, a set of guidelines for sepsis, on the recognition, early investigation and management of septic patients in the emergency department. METHOD(S): We conducted a comparative prospective cohort study of patients who presented with suspected sepsis pre- and post-implementation of the Sepsis Pathway. Patients where the Sepsis Pathway was used were identified and followed prospectively to analyse outcomes. This group was compared to a pre-intervention control group who were identified retrospectively before the Sepsis Pathway was implemented to determine if there was any difference in outcomes. RESULT(S): A total of 109 patients were identified to be septic in the emergency department following the implementation of the Sepsis Pathway. Of these, 52 cases involved the initiation and completion of the Sepsis Pathway. One hundred and fifty-seven cases were identified in the pre-intervention group of which 18 cases were excluded. The time to antibiotic administration decreased from 182 to 75 minutes (p<0.00001). The proportion of cases where antibiotics were given within the hour was higher in the pathway group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69-13.81, p<0.0001). Similarly, the time to lactate measurement decreased from 64 minutes to 54.5 minutes (p=0.0117) and the proportion of cases where lactate was measured improved from 64% to 92.3% (p=0.0005). Blood culture rates improved from 79.1% to 100%. CONCLUSION(S): The implementation of the Sepsis Pathway improved time taken to perform investigations and manage patients with sepsis. Although it had improved, there was still a delay in recognition of sepsis and initiation of investigations and management, demonstrating that further strategies need to be employed to reduce poor outcomes associated with sepsis

OBJECTIVE: The objective of this systematic review was to examine the effects of different balance exercise interventions compared with non-balance exercise controls on balance task performance in older adults. DESIGN: Systematic review. DATA SOURCES: Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Scopus and Cochrane Database of Systematic Reviews were searched until July 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of randomised trials of balance exercise interventions for older adults were identified for extraction of eligible randomised trials. Eligibility criteria for inclusion of randomised trials in meta-analyses were comparison of a balance exercise intervention with a control group that did not perform balance exercises, report of at least one end-intervention balance outcome measurement that was consistent with the five subgroups of balance exercise identified, and full-text article available in English. RESULT(S): Ninety-five trials were included in meta-analyses and 80 in meta-regressions. For four balance exercise types (control centre of mass, multidimensional, mobility and reaching), significant effects for balance exercise interventions were found in meta-analyses (standardised mean difference (SMD) 0.31-0.50), however with considerable heterogeneity in observed effects (I2: 50.4%-80.6%). Risk of bias assessments (Physiotherapy Evidence Database score and funnel plots) did not explain heterogeneity. One significant relationship identified in the meta-regressions of SMD and balance exercise frequency, time and duration explained 2.1% of variance for the control centre of mass subgroup. CONCLUSION(S): Limitations to this study included the variability in design of balance interventions, incomplete reporting of data and statistical heterogeneity. The design of balance exercise programmes provides inadequate explanation of the observed benefits of these interventions.Copyright © Article

BACKGROUND: This study describes the temporal changes in risk profiles and outcomes among patients with aortic stenosis (AS) undergoing surgical aortic valve replacement (SAVR) in Australia between 2002 and 2015. METHOD(S): Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database, we identified first-recorded SAVR for AS over 14 years. Patients' surgical risk profiles, procedures, 30-day and 12-month outcomes were summarized before and after the introduction of transcatheter aortic valve implantation in Australia, in 2008. We applied multivariable regression models to investigate the changes over time on risk-adjusted 30-day mortality, re-hospitalization and 12-month mortality. RESULT(S): We identify a total of 18147 patients with AS who underwent SAVR; mostly men (64%) with a mean age of 72years. The proportion of major cardiac surgeries devoted to SAVR increased from 14% in 2002 to 20% in 2015. More SAVRs were performed electively (80% in 2002 versus 86% in 2015), and the recipients were at lower surgical risk (mean multi-risk score 3.9% in 2002 versus 3.0% in 2015). The use of bioprosthetic aortic valves increased over time (67% in 2002 to 88% in 2015). We found no significant changes in 30-day mortality, a significant decrease in 30-day readmission and minor fluctuations in 12-month mortality over the study period. CONCLUSION(S): SAVR comprises an increasingly larger proportion of all adult cardiac surgeries in Australia. There has been a greater use of bioprosthetic aortic valves, a fall in 30-day readmission but no significant changes in mortality.Copyright © 2019 Royal Australasian College of Surgeons.

OBJECTIVE: To identify discharge medications, especially psychotropic medications that are associated with falls, amongst older adults within 6 months following hospitalisation. METHOD(S): Negative binomial regression was used to examine relationships between discharge medications and falls in older post-hospitalised adults. Multiple regression that considered falls risk factors at discharge was performed. RESULT(S): Data for 267 participants showed that discharge medications were not independently associated with falls postdischarge after adjustment for other falls risk factors. Male gender (adjusted incidence rate ratio [95% confidence interval, CI]) 2.15 [1.36-3.40]), higher depression scores (1.14 [1.05-1.25]) and co-morbidity of neurological disease other than stroke (5.98 [3.08-11.60]) were independently associated with an increased rate of falls. Higher depression scores (1.20 [1.11-1.31]) and co-morbidity of cancer (1.97 [1.20-3.25]) were independently associated with an increased rate of injurious falls in the 6 months postdischarge. CONCLUSION(S): Falls prevention strategies, other than hospital discharge medication management in the postdischarge older adults, warrant investigation.Copyright © 2019 AJA Inc.

High-throughput and rapid serology assays to detect the antibody response specific to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in human blood samples are urgently required to improve our understanding of the effects of COVID-19 across the world. Short-term applications include rapid case identification and contact tracing to limit viral spread, while population screening to determine the extent of viral infection across communities is a longer-term need. Assays developed to address these needs should match the ASSURED criteria. We have identified agglutination tests based on the commonly employed blood typing methods as a viable option. These blood typing tests are employed in hospitals worldwide, are high-throughput, fast (10-30 min), and automated in most cases. Herein, we describe the application of agglutination assays to SARS-CoV-2 serology testing by combining column agglutination testing with peptide-antibody bioconjugates, which facilitate red cell cross-linking only in the presence of plasma containing antibodies against SARS-CoV-2. This simple, rapid, and easily scalable approach has immediate application in SARS-CoV-2 serological testing and is a useful platform for assay development beyond the COVID-19 pandemic.

BACKGROUND: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia. METHOD(S): We retrospectively reviewed data from all patients aged >=80 years who underwent curative-intent resection for NSCLC over 12years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival. RESULT(S): Two hundred patients aged >=80 years underwent curative-intent resections. Mortality at 30 and 120days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those >=83years, at 30days (6.8% versus 0.8%, P = 0.044) and 120days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients >=83years requiring lobectomy, compared to sub-lobar resection at 120days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02). CONCLUSION(S): In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.Copyright © 2018 Royal Australasian College of Surgeons.

Background: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. Method(s): A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. Result(s): There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. Conclusion(s): We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.Copyright © 2020 The Author(s).

AIM: Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. We aimed to study the effect of the Sepsis Pathway Programme, a set of guidelines for sepsis, on the recognition, early investigation and management of septic patients in the emergency department. METHOD(S): We conducted a comparative prospective cohort study of patients who presented with suspected sepsis pre- and post-implementation of the Sepsis Pathway. Patients where the Sepsis Pathway was used were identified and followed prospectively to analyse outcomes. This group was compared to a pre-intervention control group who were identified retrospectively before the Sepsis Pathway was implemented to determine if there was any difference in outcomes. RESULT(S): A total of 109 patients were identified to be septic in the emergency department following the implementation of the Sepsis Pathway. Of these, 52 cases involved the initiation and completion of the Sepsis Pathway. One hundred and fifty-seven cases were identified in the pre-intervention group of which 18 cases were excluded. The time to antibiotic administration decreased from 182 to 75 minutes (p<0.00001). The proportion of cases where antibiotics were given within the hour was higher in the pathway group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69-13.81, p<0.0001). Similarly, the time to lactate measurement decreased from 64 minutes to 54.5 minutes (p=0.0117) and the proportion of cases where lactate was measured improved from 64% to 92.3% (p=0.0005). Blood culture rates improved from 79.1% to 100%. CONCLUSION(S): The implementation of the Sepsis Pathway improved time taken to perform investigations and manage patients with sepsis. Although it had improved, there was still a delay in recognition of sepsis and initiation of investigations and management, demonstrating that further strategies need to be employed to reduce poor outcomes associated with sepsis

OBJECTIVE: The objective of this systematic review was to examine the effects of different balance exercise interventions compared with non-balance exercise controls on balance task performance in older adults. DESIGN: Systematic review. DATA SOURCES: Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Scopus and Cochrane Database of Systematic Reviews were searched until July 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of randomised trials of balance exercise interventions for older adults were identified for extraction of eligible randomised trials. Eligibility criteria for inclusion of randomised trials in meta-analyses were comparison of a balance exercise intervention with a control group that did not perform balance exercises, report of at least one end-intervention balance outcome measurement that was consistent with the five subgroups of balance exercise identified, and full-text article available in English. RESULT(S): Ninety-five trials were included in meta-analyses and 80 in meta-regressions. For four balance exercise types (control centre of mass, multidimensional, mobility and reaching), significant effects for balance exercise interventions were found in meta-analyses (standardised mean difference (SMD) 0.31-0.50), however with considerable heterogeneity in observed effects (I2: 50.4%-80.6%). Risk of bias assessments (Physiotherapy Evidence Database score and funnel plots) did not explain heterogeneity. One significant relationship identified in the meta-regressions of SMD and balance exercise frequency, time and duration explained 2.1% of variance for the control centre of mass subgroup. CONCLUSION(S): Limitations to this study included the variability in design of balance interventions, incomplete reporting of data and statistical heterogeneity. The design of balance exercise programmes provides inadequate explanation of the observed benefits of these interventions.Copyright © Article

Background: We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection. Methods: LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined. Results: Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss. Conclusions: Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.