Re-interpreting the evidence for bipedality in Homo floresiensis

The unveiling in October 2004 of the remains of a pygmy-sized hominin recovered from a cave on the island of Flores, Indonesia, sparked an intense series of debates within the palaeoanthropology community. The discoverers diagnosed it to be a new species of Homo, which they called Homo floresiensis, and they interpreted the postcranial morphology as being 'consistent with human-like obligate bipedalism'. We have examined the morphology with the aim of determining whether biomechanical evidence supports the claim that this hominin - known as LB1 - was indeed habitually bipedal. LB1's innominate bone differs from that of modern humans through the marked lateral flaring of the ilium, while her femur has a small head and a relatively long neck. Although these features are also found in australopithecines and are commonly regarded as 'primitive' traits, we concluded that none would have prevented her from exhibiting an efficient, bipedal gait. Having established that LB1 walked on two legs, we employed the principle of dynamic similarity to speculate how she might have walked. Assuming the gait of LB1 was dynamically similar to that of modern Homo sapiens, we used known dimensionless parameters, together with her leg length (0.55 m), to estimate her fundamental gait parameters : step length = 0.45 m, step frequency = 2.48 steps / second and speed = 1.11 m/s. Our review has provided insights regarding the way in which LB1 and her fellow diminutive hominins walked about the island of Flores over 18 000 years ago

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Kongsfjorden as harbinger of the future Arctic: knowns, unknowns and research priorities

Due to its year-round accessibility and excellent on-site infrastructure, Kongsfjorden and the Ny-Ålesund Research and Monitoring Facility have become established as a primary location to study the impact of environmental change on Arctic coastal ecosystems. Due to its location right at the interface of Arctic and Atlantic oceanic regimes, Kongsfjorden already experiences large amplitudes of variability in physico/chemical conditions and might, thus, be considered as an early warning indicator of future changes, which can then be extrapolated in a pan-Arctic perspective. Already now, Kongsfjorden represents one of the best-studied Arctic fjord systems. However, research conducted to date has concentrated largely on small disciplinary projects, prompting the need for a higher level of integration of future research activities. This contribution, thus, aims at identifying gaps in knowledge and research priorities with respect to ecological and adaptive responses to Arctic ecosystem changes. By doing so we aim to provide a stimulus for the initiation of new international and interdisciplinary research initiatives

Worldwide comparison of survival from childhood leukaemia for 1995\u20132009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89\u2008828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0\u201314 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995\u201399, 2000\u201304, and 2005\u201309), sex, and age at diagnosis (<1, 1\u20134, 5\u20139, and 10\u201314 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89\u2008828 children from 198 registries in 53 countries. During 1995\u201399, 5-year age-standardised net survival for all lymphoid leukaemias combined ranged from 10\ub76% (95% CI 3\ub71\u201318\ub72) in the Chinese registries to 86\ub78% (81\ub76\u201392\ub70) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005\u201309, when age-standardised survival for lymphoid leukaemias ranged from 52\ub74% (95% CI 42\ub78\u201361\ub79) in Cali, Colombia, to 91\ub76% (89\ub75\u201393\ub76) in the German registries, and for AML ranged from 33\ub73% (18\ub79\u201347\ub77) in Bulgaria to 78\ub72% (72\ub70\u201384\ub73) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000\u201304 and 2005\u201309. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1\u20134 and 5\u20139 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival. Funding Canadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer Institute New South Wales, Cancer Research UK, US Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, and the University of Kentucky

Impact of malignancy on outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EURObservational research programme in atrial fibrillation general long-term registry

Background: The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management. Purpose: To evaluate the outcomes of patients with active or prior malignancy in a contemporary cohort of European AF patients. Methods: Patients enrolled in the EURObservational Research Programme in AF General Long-Term Registry were categorized into 3 categories: No Malignancy (NoMal), Prior Malignancy (PriorMal) and Active Malignancy (ActiveMal). The primary outcomes were all-cause death and the composite outcome MACE. Results: A total of 10 383 patients were analysed. Of these, 9597 (92.4%) were NoMal patients, 577 (5.6%) PriorMal and 209 (2%) ActiveMal. Lack of any antithrombotic treatment was more prevalent in ActiveMal patients (12.4%) as compared to other groups (5.0% vs 6.3% for PriorMal and NoMal, p <.001). After a median follow-up of 730 days, there were 982 (9.5%) deaths and 950 (9.7%) MACE events. ActiveMal was independently associated with a higher risk for all-cause death (HR 2.90, 95% CI 2.23–3.76) and MACE (HR 1.54, 95% CI 1.03–2.31), as well as any haemorrhagic events and major bleeding (OR 2.42, 95% CI 1.49–3.91 and OR 4.18, 95% CI 2.49–7.01, respectively). Use of oral anticoagulants was not significantly associated with a higher risk for all-cause death or bleeding in ActiveMal patients. Conclusions: In a large contemporary cohort of AF patients, active malignancy was independently associated with all-cause death, MACE and haemorrhagic events. Use of anticoagulants was not associated with a higher risk of all-cause death in patients with active malignancies

Epidemiology and impact of frailty in patients with atrial fibrillation in Europe

Background: Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. Objectives: We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. Methods: A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. Results: Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55–0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. Conclusions: In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones