Mathematics of random growing interfaces

We establish a thermodynamic limit and Gaussian fluctuations for the height and surface width of the random interface formed by the deposition of particles on surfaces. The results hold for the standard ballistic deposition model as well as the surface relaxation model in the off-lattice setting. The results are proved with the aid of general limit theorems for stabilizing functionals of marked Poisson point processes.Comment: 12 page

Differences in biomechanical determinants of ACL injury risk in Change of Direction tasks between males and females: A systematic review and meta-analysis

Background Change of direction (COD) movements are associated with non-contact anterior cruciate ligament (ACL) injuries in multidirectional sports. Females appear at increased risk compared to males, which could be attributable to whole body kinematic strategies and greater multiplanar knee joint loads (KJLs) during COD which can increase ACL loading. Objective The aim of this systematic review and meta-analysis was to examine and quantitatively synthesise the evidence for differences between males and females regarding KJLs and their biomechanical determinants (whole body kinematic strategies determining KJLs) during COD tasks. Methods Databases including SPORTDiscus, Web of Science, and PubMed were systematically searched (July 2021–June 2023) for studies that compared differences in knee joint loads and biomechanical determinants of KJLs during COD between males and females. Inclusion criteria were: (1) females and males with no prior history of ACL injury (18–40 years); (2) examined biomechanical determinants of KJLs and/ or KJLs during COD tasks > 20°; (3) compared ≥ 1 outcome measure between males and females. Studies published between 2000 and 2023 examining a cutting task > 20° with a preceding approach run that compared KJLs or the whole body multiplanar kinematics associated with them, between sexes, using three-dimensional motion analysis. Results This meta-analysis included 17 studies with a pooled sample size of 451 participants (227 males, 224 females). Meta-analysis revealed females displayed significantly less peak knee flexion during stance (SMD: 0.374, 95% CI 0.098–0.649, p = 0.008, I2: 0%); greater knee abduction at initial contact (IC) (SMD: 0.687, 95% CI 0.299–1.076, p = 0.001, I2: 55%); less hip internal rotation (SMD: 0.437, 95% CI 0.134–0.741, p = 0.005, I2: 34%) and hip abduction at IC (SMD: −0.454, 95% CI 0.151–0.758, p = 0.003, I2: 33%). No significant differences were observed between males and females for any internal or externally applied KJLs. All retrieved studies failed to control for strength, resistance training or skill history status. Conclusion No differences were observed in KJLs between males and females despite females displaying greater knee abduction at IC and less peak knee flexion during the stance phase of CODs, which are visual characteristics of non-contact ACL injury. Further research is required to examine if this translates to a similar injury risk, considering morphological differences in strain characteristics of the ACL between males and females. This observation may in part explain the disproportionate ACL injury incidence in female multidirectional athletes. Further higher quality controlled research is required whereby participants are matched by skill training history, resistance training history and strength status to ensure an appropriate comparison between males and females

Learned vocal variation is associated with abrupt cryptic genetic change in a parrot species complex

<div><p>Contact zones between subspecies or closely related species offer valuable insights into speciation processes. A typical feature of such zones is the presence of clinal variation in multiple traits. The nature of these traits and the concordance among clines are expected to influence whether and how quickly speciation will proceed. Learned signals, such as vocalizations in species having vocal learning (e.g. humans, many birds, bats and cetaceans), can exhibit rapid change and may accelerate reproductive isolation between populations. Therefore, particularly strong concordance among clines in learned signals and population genetic structure may be expected, even among continuous populations in the early stages of speciation. However, empirical evidence for this pattern is often limited because differences in vocalisations between populations are driven by habitat differences or have evolved in allopatry. We tested for this pattern in a unique system where we may be able to separate effects of habitat and evolutionary history. We studied geographic variation in the vocalizations of the crimson rosella (<em>Platycercus elegans</em>) parrot species complex. Parrots are well known for their life-long vocal learning and cognitive abilities. We analysed contact calls across a <em>ca</em> 1300 km transect encompassing populations that differed in neutral genetic markers and plumage colour. We found steep clinal changes in two acoustic variables (fundamental frequency and peak frequency position). The positions of the two clines in vocal traits were concordant with a steep cline in microsatellite-based genetic variation, but were discordant with the steep clines in mtDNA, plumage and habitat. Our study provides new evidence that vocal variation, in a species with vocal learning, can coincide with areas of restricted gene flow across geographically continuous populations. Our results suggest that traits that evolve culturally can be strongly associated with reduced gene flow between populations, and therefore may promote speciation, even in the absence of other barriers.</p> </div

Differences in biomechanical determinants of ACL injury risk in change of direction tasks between males and females: a systematic review and meta-analysis

Background Change of direction (COD) movements are associated with non-contact anterior cruciate ligament (ACL) injuries in multidirectional sports. Females appear at increased risk compared to males, which could be attributable to whole body kinematic strategies and greater multiplanar knee joint loads (KJLs) during COD which can increase ACL loading. Objective The aim of this systematic review and meta-analysis was to examine and quantitatively synthesise the evidence for differences between males and females regarding KJLs and their biomechanical determinants (whole body kinematic strategies determining KJLs) during COD tasks. Methods Databases including SPORTDiscus, Web of Science, and PubMed were systematically searched (July 2021–June 2023) for studies that compared differences in knee joint loads and biomechanical determinants of KJLs during COD between males and females. Inclusion criteria were: (1) females and males with no prior history of ACL injury (18–40 years); (2) examined biomechanical determinants of KJLs and/ or KJLs during COD tasks > 20°; (3) compared ≥ 1 outcome measure between males and females. Studies published between 2000 and 2023 examining a cutting task > 20° with a preceding approach run that compared KJLs or the whole body multiplanar kinematics associated with them, between sexes, using three-dimensional motion analysis. Results This meta-analysis included 17 studies with a pooled sample size of 451 participants (227 males, 224 females). Meta-analysis revealed females displayed significantly less peak knee flexion during stance (SMD: 0.374, 95% CI 0.098–0.649, p = 0.008, I2: 0%); greater knee abduction at initial contact (IC) (SMD: 0.687, 95% CI 0.299–1.076, p = 0.001, I2: 55%); less hip internal rotation (SMD: 0.437, 95% CI 0.134–0.741, p = 0.005, I2: 34%) and hip abduction at IC (SMD: −0.454, 95% CI 0.151–0.758, p = 0.003, I2: 33%). No significant differences were observed between males and females for any internal or externally applied KJLs. All retrieved studies failed to control for strength, resistance training or skill history status. Conclusion No differences were observed in KJLs between males and females despite females displaying greater knee abduction at IC and less peak knee flexion during the stance phase of CODs, which are visual characteristics of non-contact ACL injury. Further research is required to examine if this translates to a similar injury risk, considering morphological differences in strain characteristics of the ACL between males and females. This observation may in part explain the disproportionate ACL injury incidence in female multidirectional athletes. Further higher quality controlled research is required whereby participants are matched by skill training history, resistance training history and strength status to ensure an appropriate comparison between males and females

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Differences in Biomechanical Determinants of ACL Injury Risk in Change of Direction Tasks Between Males and Females: A Systematic Review and Meta-Analysis

Background: Change of direction (COD) movements are associated with non-contact anterior cruciate ligament (ACL) injuries in multidirectional sports. Females appear at increased risk compared to males, which could be attributable to whole body kinematic strategies and greater multiplanar knee joint loads (KJLs) during COD which can increase ACL loading. Objective: The aim of this systematic review and meta-analysis was to examine and quantitatively synthesise the evidence for differences between males and females regarding KJLs and their biomechanical determinants (whole body kinematic strategies determining KJLs) during COD tasks. Methods: Databases including SPORTDiscus, Web of Science, and PubMed were systematically searched (July 2021–June 2023) for studies that compared differences in knee joint loads and biomechanical determinants of KJLs during COD between males and females. Inclusion criteria were: (1) females and males with no prior history of ACL injury (18–40 years); (2) examined biomechanical determinants of KJLs and/ or KJLs during COD tasks > 20°; (3) compared ≥ 1 outcome measure between males and females. Studies published between 2000 and 2023 examining a cutting task > 20° with a preceding approach run that compared KJLs or the whole body multiplanar kinematics associated with them, between sexes, using three-dimensional motion analysis. Results: This meta-analysis included 17 studies with a pooled sample size of 451 participants (227 males, 224 females). Meta-analysis revealed females displayed significantly less peak knee flexion during stance (SMD: 0.374, 95% CI 0.098–0.649, p = 0.008, I2: 0%); greater knee abduction at initial contact (IC) (SMD: 0.687, 95% CI 0.299–1.076, p = 0.001, I2: 55%); less hip internal rotation (SMD: 0.437, 95% CI 0.134–0.741, p = 0.005, I2: 34%) and hip abduction at IC (SMD: −0.454, 95% CI 0.151–0.758, p = 0.003, I2: 33%). No significant differences were observed between males and females for any internal or externally applied KJLs. All retrieved studies failed to control for strength, resistance training or skill history status. Conclusion: No differences were observed in KJLs between males and females despite females displaying greater knee abduction at IC and less peak knee flexion during the stance phase of CODs, which are visual characteristics of non-contact ACL injury. Further research is required to examine if this translates to a similar injury risk, considering morphological differences in strain characteristics of the ACL between males and females. This observation may in part explain the disproportionate ACL injury incidence in female multidirectional athletes. Further higher quality controlled research is required whereby participants are matched by skill training history, resistance training history and strength status to ensure an appropriate comparison between males and females

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.