Impact of a keto diet on symptoms of Parkinson's disease, biomarkers, depression, anxiety and quality of life: a longitudinal study.

Aim: Evidence suggests low-carbohydrate diets (LCHF) may assist in treating neurodegenerative diseases such as Parkinson's disease (PD); however, gaps exist in the literature. Patients & methods: We conducted a small 24-week pilot study to investigate the effects of an LCHF diet on motor and nonmotor symptoms, health biomarkers, anxiety, and depression in seven people with PD. We also captured patient experiences during the process (quality of life [QoL]). Results: Participants reported improved biomarkers, enhanced cognition, mood, motor and nonmotor symptoms, and reduced pain and anxiety. Participants felt improvements enhanced their QoL. Conclusion: We conclude that an LCHF intervention is safe, feasible, and potentially effective in mitigating the symptoms of this disorder. However, more extensive randomized controlled studies are needed to create generalizable recommendations.

[Box: see text].

A national multicentre study of outcomes and patient satisfaction with the virtual fracture clinic and the influence of the COVID-19 pandemic: The MAVCOV study.

BACKGROUND: Virtual fracture clinics (VFCs) are advocated by the British Orthopaedic Association Standards for Trauma (BOAST). We aimed to assess the impact of the transition from face-to-face fracture clinic review and identify any change in clinical outcome and patient satisfaction. METHODS: A national, cross-sectional cohort study of VFCs across the UK over two separate two-week periods pre- and during the first UK COVID-19 lockdown was undertaken. Data comprising patient and injury characteristics, unplanned reattendance and complications within three months following discharge from VFC were collected by local collaborators. Telephone questionnaires were conducted to determine patient satisfaction and patient-reported outcome for patients discharged without face-to-face consultation. The primary outcome measure was the percentage of unplanned reattendances after direct discharge from VFC. RESULTS: Data was analysed for 51 UK VFCs comprising 6134 patients from the pre-pandemic group (06/05/2019-19/05/2019) and 4366 patients from the first UK lockdown (04/05/2020-17/05/2020). During lockdown, the rate of direct discharge from VFC increased significantly (odds ratio (OR) 2.01, p<0.001) from 30 % (n = 1856/6134) to 46 % (n = 2021/4366). The rate of compliance with BOAST guidance recommending fracture clinic review within three days increased (OR 1.93, p<0.001) from 82 % (n = 5003/6134) to 89 % (n = 3883/4366). There were no differences in the rates of unplanned reattendance (6 % pre- and 7 % during lockdown, p = 0.281) or complications (0.2 % for both, p = 0.815). There were 1527/3877 patients discharged without face-to-face review from VFC who completed telephone questionnaires (mean follow-up 18-months in pre-pandemic group and 6-months in lockdown group). Satisfaction was high in both cohorts (80 % pre- and 76 % lockdown, p = 0.093). Dissatisfaction was associated with an unplanned reattendance (p<0.001) or a missed injury (p<0.05). CONCLUSION: Despite a significant rise in direct discharge from VFC, there was no significant change in unplanned attendances, complications, or patient satisfaction. However, there are factors associated with dissatisfaction and these should be considered in the evolution of VFC.

Acute ischemic stroke outcomes in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Although patients with COVID-19 have a higher risk of acute ischemic stroke (AIS), the impact on stroke outcomes remains uncertain. AIMS: To determine the clinical outcomes of patients with AIS and COVID-19 (AIS-COVID+). METHODS: We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our protocol was registered with the International Prospective Register of Systematic Reviews (CRD42020211977). Systematic searches were last performed on June 3, 2021 in EMBASE, PubMed, Web-of-Science, Scopus, and CINAHL Databases. INCLUSION CRITERIA: (1) studies reporting outcomes on AIS-COVID+; (2) original articles published in 2020 or later; (3) study participants aged ≥18 years. EXCLUSION CRITERIA: (1) case reports with <5 patients, abstracts, review articles; (2) studies analyzing novel interventions. Risk of bias was assessed using the Mixed Methods Appraisal Tool. Random-effects models estimated the pooled OR and 95% confidence intervals (95% CI) for mortality, modified Rankin Scale (mRS) score, length of stay (LOS), and discharge disposition. RESULTS: Of the 43 selected studies, 46.5% (20/43) reported patients with AIS without COVID-19 (AIS-COVID-) for comparison. Random-effects model included 7294 AIS-COVID+ and 158 401 AIS-COVID-. Compared with AIS-COVID-, AIS-COVID+ patients had higher in-hospital mortality (OR=3.87 (95% CI 2.75 to 5.45), P<0.001), less mRS scores 0-2 (OR=0.53 (95% CI 0.46 to 0.62), P<0.001), longer LOS (mean difference=4.21 days (95% CI 1.96 to 6.47), P<0.001), and less home discharge (OR=0.31 (95% CI 0.21 to 0.47), P<0.001). CONCLUSIONS: Patients with AIS-COVID had worse outcomes, with almost fourfold increased mortality, half the odds of mRS scores 0-2, and one-third the odds of home discharge. These findings confirm the significant impact of COVID-19 on early stroke outcomes.

Pre-existing knee osteoarthritis and severe joint depression are associated with the need for total knee arthroplasty after tibial plateau fracture in patients aged over 60 years.

Aims: This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults. Methods: This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded. Results: Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA. Conclusion: Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs.

Tibial plateau fractures in older adults are associated with a clinically significant deterioration in health-related quality of life.

To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients. We undertook a retrospective, case-control study of 67 patients at mean 3.5 years (SD 1.3; 1.3 to 6.1) after TPF (47 patients underwent fixation, and 20 nonoperative management). Patients completed EuroQol five-dimension three-level (EQ-5D-3L) questionnaire, Lower Limb Function Scale (LEFS), and Oxford Knee Scores (OKS) for current and recalled prefracture status. Propensity score matching for age, sex, and deprivation in a 1:5 ratio was performed using patient level data from the Health Survey for England to obtain a control group for HRQoL comparison. The primary outcome was the difference in actual (TPF cohort) and expected (matched control) EQ-5D-3L score after TPF. TPF patients had a significantly worse EQ-5D-3L utility (mean difference (MD) 0.09, 95% confidence interval (CI) 0.00 to 0.16; p < 0.001) following their injury compared to matched controls, and had a significant deterioration (MD 0.140, 95% CI 0 to 0.309; p < 0.001) relative to their preoperative status. TPF patients had significantly greater pre-fracture EQ-5D-3L scores compared to controls (p = 0.003), specifically in mobility and pain/discomfort domains. A decline in EQ-5D-3L greater than the minimal important change of 0.105 was present in 36/67 TPF patients (53.7%). Following TPF, OKS (MD -7; interquartile range (IQR) -1 to -15) and LEFS (MD -10; IQR -2 to -26) declined significantly (p < 0.001) from pre-fracture levels. Of the 12 elements of fracture care assessed, the most important to patients were getting back to their own home, having a stable knee, and returning to normal function. TPFs in older adults were associated with a clinically significant deterioration in HRQoL compared to preinjury level and age, sex, and deprivation matched controls for both undisplaced fractures managed nonoperatively and displaced or unstable fractures managed with internal fixation.

Phase evolution and arsenic immobilization of arsenate-bearing amorphous calcium phosphate.

The formation of As(V) substituted hydroxylapatite (HAP) has a vital influence on the fate of As(V) in the environment. However, despite growing evidence showing that HAP crystallizes in vivo and in vitro with amorphous calcium phosphate (ACP) as a precursor, a knowledge gap exists concerning the transformation from arsenate-bearing ACP (AsACP) to arsenate-bearing HAP (AsHAP). Here we synthesized AsACP nano-particles with varied As contents and investigated the arsenic incorporation during their phase evolution. The phase evolution results showed that the transformation process of AsACP to AsHAP could be divided into three Stages. A higher As(V) loading significantly delayed the transformation of AsACP, increased the distortion degree, and decreased the crystallinity of AsHAP. NMR result showed that the PO43- tetrahedral is geometrically preserved when PO43- is substituted by AsO43-. From AsACP to AsHAP, the As-substitution led to the transformation inhibition and As(V) immobilization.

Estimating the lifetime risk of a false positive screening test result.

False positive results in screening tests have potentially severe psychological, medical, and financial consequences for the recipient. However, there have been few efforts to quantify how the risk of a false positive accumulates over time. We seek to fill this gap by estimating the probability that an individual who adheres to the U.S. Preventive Services Task Force (USPSTF) screening guidelines will receive at least one false positive in a lifetime. To do so, we assembled a data set of 116 studies cited by the USPSTF that report the number of true positives, false negatives, true negatives, and false positives for the primary screening procedure for one of five cancers or six sexually transmitted diseases. We use these data to estimate the probability that an individual in one of 14 demographic subpopulations will receive at least one false positive for one of these eleven diseases in a lifetime. We specify a suitable statistical model to account for the hierarchical structure of the data, and we use the parametric bootstrap to quantify the uncertainty surrounding our estimates. The estimated probability of receiving at least one false positive in a lifetime is 85.5% (±0.9%) and 38.9% (±3.6%) for baseline groups of women and men, respectively. It is higher for subpopulations recommended to screen more frequently than the baseline, including more vulnerable groups such as pregnant women and men who have sex with men. Since screening technology is imperfect, false positives remain inevitable. The high lifetime risk of a false positive reveals the importance of educating patients about this phenomenon.

What Is the Safe Window from Definitive Fixation to Flap Coverage in Type 3B Open Tibia Fractures? Supporting Plastics and Orthopaedics Alliance in Reducing Trauma Adverse Events (SPARTA).

OBJECTIVES: To delineate whether a "safe" window exists for timing from definitive fixation to definitive soft tissue coverage in the treatment of open tibial diaphyseal fractures requiring flap coverage. DESIGN: International multicenter, retrospective comparative cohort study. PATIENTS/PARTICIPANTS: Three hundred and seventy-three (n = 373) patients who sustained an open tibial shaft fracture requiring flap coverage. METHODS: We evaluated the deep infection rates based on the timing between the definitive fixation and flap coverage. We determined several intervals of time from the day of definitive fixation (regardless of time from injury) and flap coverage. If performed on the same operative setting these were considered day 0. We evaluated coverage after 2 and 5 days from definitive fixation based on time versus infection rate curve inflection points. We adjusted for time to debridement and antibiotics within an hour. MAIN OUTCOME MEASUREMENT: Deep infection after definitive fixation and flap coverage. RESULTS: The mean age of the cohort was 42.4 years (SD = 18.2) and 270 were male (72.4%). The deep infection rate after flap coverage was 20.6% (77/373). Definitive fixation to flap coverage time of up to 2 days was not associated with an increased risk of infection [relative risk (RR) = 1.12; 95% confidence interval, 0.92-1.37; P = 0.26]. There was an increased risk of deep infection for more than 2 days (RR = 1.59) and >5 days (RR = 1.64). CONCLUSION: This study observed a "safe" window of up to 2 days between definitive fixation and flap coverage in open tibial shaft fractures requiring coverage before a statistical increase in risk of deep infection rate occurred. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Does Advanced Imaging Aid in the Preoperative Evaluation of Patients With Moyamoya Disease?

Background Moyamoya disease is characterized by progressive nonatherosclerotic stenosis and eventual occlusion of the supraclinoid cerebral arteries with the associated development of abnormal collateral vessels. Treatment of moyamoya disease revolves around restoring cerebral blood flow (CBF) distal to the steno-occlusive disease. Numerous modalities can be used to assess hemodynamic parameters. We sought to determine the impact of preoperative imaging on surgical decision-making. Methods A retrospective review was performed of all patients seen with the diagnosis of moyamoya. Patients were grouped on presentation based on CT/MRI findings of infarction, hemorrhage, or normal. Patients who did not have all of the preoperative tests were excluded. Preoperative radiological results were dichotomized as either normal or abnormal. Results During a five-year period, 34 patients with moyamoya met the inclusion criteria. All patients had an abnormal magnetic resonance angiography (MRA) Non-invasive Optimal Vessel Analysis (NOVA; VasSol, Inc, River Forest, IL). Three patients had normal initial MRI. All symptomatic patients had abnormal preoperative workup and underwent revascularization, as all were found to have abnormal single photon emission computed tomography (SPECT). The only occasion where the decision for surgery or type of surgery was influenced by imaging findings was in patients with nonclassical or minimal symptoms. Conclusion Although hemodynamic imaging studies can aid in establishing a preoperative baseline of CBF and cerebral vascular reserve (CVR) for follow-up studies, the true implication of these tests in the preoperative evaluation of clearly symptomatic moyamoya patients is debatable. In asymptomatic/mildly symptomatic patients, hemodynamic studies are necessary to determine the need for treatment. For symptomatic patients, surgery can be performed without an exhaustive and costly preoperative hemodynamic evaluation.

Endocranial ontogeny and evolution in early Homo sapiens: The evidence from Herto, Ethiopia.

Fossils and artifacts from Herto, Ethiopia, include the most complete child and adult crania of early Homo sapiens. The endocranial cavities of the Herto individuals show that by 160,000 y ago, brain size, inferred from endocranial size, was similar to that seen in modern human populations. However, endocranial shape differed from ours. This gave rise to the hypothesis that the brain itself evolved substantially during the past ∼200,000 y, possibly in tandem with the transition from Middle to Upper Paleolithic techno-cultures. However, it remains unclear whether evolutionary changes in endocranial shape mostly reflect changes in brain morphology rather than changes related to interaction with maxillofacial morphology. To discriminate between these effects, we make use of the ontogenetic fact that brain growth nearly ceases by the time the first permanent molars fully erupt, but the face and cranial base continue to grow until adulthood. Here we use morphometric data derived from digitally restored immature and adult H. sapiens fossils from Herto, Qafzeh, and Skhul (HQS) to track endocranial development in early H. sapiens. Until the completion of brain growth, endocasts of HQS children were similar in shape to those of modern human children. The similarly shaped endocasts of fossil and modern children indicate that our brains did not evolve substantially over the past 200,000 y. Differences between the endocranial shapes of modern and fossil H. sapiens adults developed only with continuing facial and basicranial growth, possibly reflecting substantial differences in masticatory and/or respiratory function.

A powder XRD, solid state NMR and calorimetric study of the phase evolution in mechanochemically synthesized dual cation (Csx(CH3NH3)1-x)PbX3 lead halide perovskite systems.

Methylammonium (MA+) lead halide perovskites (MAPbX3) have been widely investigated for photovoltaic applications, with the addition of Cs improving structural and thermal stability. This study reports the complete A site miscibility of Cs+ and MA+ cations in the lead chloride and lead bromide perovskites with nominal stoichiometric formulae (CsxMA1-x)Pb(Cl/Br)3 (x = 0, 0.13, 0.25, 0.37, 0.50, 0.63, 0.75, 0.87, 1). These suites of materials were synthesized mechanochemically as a simple, cost-effective synthesis technique to produce highly ordered, single phase particles. In contrast to previous studies using conventional synthetic routes that have reported significant solubility gaps, this solvent-free approach induces complete miscibility within the dual cation Cs+/MA+ system, with the resultant structures exhibiting high short-range and long-range atomic ordering across the entire compositional range that are devoid of solvent inclusions and disorder. The subtle structural evolution from cubic to orthorhombic symmetry reflecting PbX6 octahedral tilting was studied using complementary high resolution TEM, powder XRD, multinuclear 133Cs/207Pb/1H MAS NMR, DSC, XPS and UV/vis approaches. The phase purity and exceptional structural order were reflected in the very high resolution HRTEM images presented from particles with crystallite sizes in the ∼80-170 nm range, and the stability and long lifetimes of the Br series (10-20 min) and the Cl series (∼30 s-1 min) under the 200 kV/146 µA e- beam. Rietveld refinements associated with the room temperature PXRD study demonstrated that each system converged towards single phase compositions that were very close to the intended target stoichiometries, thus indicating the complete miscibility within these dual cation Cs+/MA+ solid solution systems. The multinuclear MAS NMR data showed a distinct sensitivity to the changing solid solution compositions across the MAPbX3-CsPbX3 partition. In particular, the 133Cs shifts demonstrated a sensitivity to the cubic-orthorhombic phase transition while the 133Cs T1s exhibited a pronounced sensitivity to the variable Cs+ cation mobility across the compositional range. Variable temperature PXRD studies facilitated the production of phase diagrams mapping the Cs+/MA+ compositional space for the (CsxMA1-x)PbCl3 and (CsxMA1-x)PbBr3 solid solution series, while Tauc plots of the UV/vis data exhibited reducing bandgaps with increasing MA+ incorporation through ranges of cubic phases where octahedral tilting was absent.

The IMPACT of COVID-19 on trauma & orthopaedic surgery provides lessons for future communicable disease outbreaks : minimum reporting standards, risk scores, fragility trauma services, and global collaboration.

Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies. Cite this article: Bone Joint Res 2022;11(6):342-345.

IMPACT-Global Hip Fracture Audit: Nosocomial infection, risk prediction and prognostication, minimum reporting standards and global collaborative audit: Lessons from an international multicentre study of 7,090 patients conducted in 14 nations during the COVID-19 pandemic.

AIMS: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. METHODS: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1st March-31st May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. RESULTS: A total of 7090 patients were included, with a mean age of 82.2 (range 50-104) years and 4959 (69.9%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) were positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p = 0.001), residential care (OR 2.15, p < 0.001), inpatient fall (OR 2.23, p = 0.003), cancer (OR 0.63, p = 0.009), ASA grades 4 (OR 1.59, p = 0.008) or 5 (OR 8.28, p < 0.001), and longer admission (OR 1.06 for each increasing day, p < 0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p < 0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p < 0.001). Increasing age (HR 1.03, p = 0.028), male sex (HR 2.35, p < 0.001), renal disease (HR 1.53, p = 0.017), and pulmonary disease (HR 1.45, p = 0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. CONCLUSION: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher 30-day mortality risk.

A Prospective, Randomized, Controlled, Two-Center, International Trial Comparing the Fibular Nail With Open Reduction and Internal Fixation for Unstable Ankle Fractures in Younger Patients.

OBJECTIVE: To compare the outcome of fibular nailing with plate fixation for unstable fractures of the ankle in a cohort of patients under the age of 65 years. SETTING: 2 international university trauma centers. PATIENTS/PARTICIPANTS: One hundred twenty-five patients who were 18-64 years of age with an acute unstable fracture of the ankle were included in the study. INTERVENTION: Patients were randomized to fixation with a fibular nail (n = 63) or plate (n = 62) and were reviewed at 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was the Olerud and Molander score at 1 year. Secondary outcomes were the rates of complications and reinterventions. RESULTS: There was no difference between the 2 groups with respect to the primary outcome measure [mean Olerud and Molander score 78.4 in the nail group vs. 80.2 in the plate group (P = 0.621)]. Wound infections occurred in 2 patients who were treated with a nail and 9 patients who were treated with a plate, but this did not reach statistical significance. No difference was seen in the overall rate of complications and reinterventions between groups [28.6% in the nail group vs. 29% in the plate group (P = 0.955)]. CONCLUSIONS: In younger patients with ankle fractures, no difference was found in the patient-reported outcome between fibular nail and plate fixation at 1 year after surgery. The fibular nail is an effective and safe option for the stabilization of ankle fractures in younger patients, although the benefits associated with reduced wound complications are not as apparent as for elderly patients. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Prediction of bleb formation in intracranial aneurysms using machine learning models based on aneurysm hemodynamics, geometry, location, and patient population.

BACKGROUND: Bleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability. OBJECTIVE: To develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population. METHODS: Cross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy. RESULTS: The final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%). CONCLUSIONS: Based on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing.

Integrative geochronology calibrates the Middle and Late Stone Ages of Ethiopia's Afar Rift.

The Halibee member of the Upper Dawaitoli Formation of Ethiopia's Middle Awash study area features a wealth of Middle and Later Stone Age (MSA and LSA) paleoanthropological resources in a succession of Pleistocene sediments. We introduce these artifacts and fossils, and determine their chronostratigraphic placement via a combination of established radioisotopic methods and a recently developed dating method applied to ostrich eggshell (OES). We apply the recently developed 230Th/U burial dating of OES to bridge the temporal gap between radiocarbon (14C) and 40Ar/39Ar ages for the MSA and provide 14C ages to constrain the younger LSA archaeology and fauna to ∼24 to 21.4 ka. Paired 14C and 230Th/U burial ages of OES agree at ∼31 ka for an older LSA locality, validating the newer method, and in turn supporting its application to stratigraphically underlying MSA occurrences previously constrained only by a maximum 40Ar/39Ar age. Associated fauna, flora, and Homo sapiens fossils are thereby now fixed between 106 ± 20 ka and 96.4 ± 1.6 ka (all errors 2σ). Additional 40Ar/39 results on an underlying tuff refine its age to 158.1 ± 11.0 ka, providing a more precise minimum age for MSA lithic artifacts, fauna, and H. sapiens fossils recovered ∼9 m below it. These results demonstrate how chronological control can be obtained in tectonically active and stratigraphically complex settings to precisely calibrate crucial evidence of technological, environmental, and evolutionary changes during the African Middle and Late Pleistocene.

Canine sexual dimorphism in Ardipithecus ramidus was nearly human-like.

Body and canine size dimorphism in fossils inform sociobehavioral hypotheses on human evolution and have been of interest since Darwin's famous reflections on the subject. Here, we assemble a large dataset of fossil canines of the human clade, including all available Ardipithecus ramidus fossils recovered from the Middle Awash and Gona research areas in Ethiopia, and systematically examine canine dimorphism through evolutionary time. In particular, we apply a Bayesian probabilistic method that reduces bias when estimating weak and moderate levels of dimorphism. Our results show that Ar. ramidus canine dimorphism was significantly weaker than in the bonobo, the least dimorphic and behaviorally least aggressive among extant great apes. Average male-to-female size ratios of the canine in Ar. ramidus are estimated as 1.06 and 1.13 in the upper and lower canines, respectively, within modern human population ranges of variation. The slightly greater magnitude of canine size dimorphism in the lower than in the upper canines of Ar. ramidus appears to be shared with early Australopithecus, suggesting that male canine reduction was initially more advanced in the behaviorally important upper canine. The available fossil evidence suggests a drastic size reduction of the male canine prior to Ar. ramidus and the earliest known members of the human clade, with little change in canine dimorphism levels thereafter. This evolutionary pattern indicates a profound behavioral shift associated with comparatively weak levels of male aggression early in human evolution, a pattern that was subsequently shared by Australopithecus and Homo.

Estimating sexual size dimorphism in fossil species from posterior probability densities.

Accurate characterization of sexual dimorphism is crucial in evolutionary biology because of its significance in understanding present and past adaptations involving reproductive and resource use strategies of species. However, inferring dimorphism in fossil assemblages is difficult, particularly with relatively low dimorphism. Commonly used methods of estimating dimorphism levels in fossils include the mean method, the binomial dimorphism index, and the coefficient of variation method. These methods have been reported to overestimate low levels of dimorphism, which is problematic when investigating issues such as canine size dimorphism in primates and its relation to reproductive strategies. Here, we introduce the posterior density peak (pdPeak) method that utilizes the Bayesian inference to provide posterior probability densities of dimorphism levels and within-sex variance. The highest posterior density point is termed the pdPeak. We investigated performance of the pdPeak method and made comparisons with the above-mentioned conventional methods via 1) computer-generated samples simulating a range of conditions and 2) application to canine crown-diameter datasets of extant known-sex anthropoids. Results showed that the pdPeak method is capable of unbiased estimates in a broader range of dimorphism levels than the other methods and uniquely provides reliable interval estimates. Although attention is required to its underestimation tendency when some of the distributional assumptions are violated, we demonstrate that the pdPeak method enables a more accurate dimorphism estimate at lower dimorphism levels than previously possible, which is important to illuminating human evolution.

Structure and surface properties of size-tuneable CsPbBr3 nanocrystals.

This investigation has characterised the structure and surface chemistry of CsPbBr3 nanocrystals with controlled diameters between 6.4 to 12.8 nm. The nanocrystals were investigated via a thorough 133Cs solid state NMR and nuclear relaxation study, identifying and mapping radially-increasing nanoscale disorder. This work has formalised 133Cs NMR as a highly sensitive probe of nanocrystal size, which can conveniently analyse nanocrystals in solid forms, as they would be utilised in optoelectronic devices. A combined multinuclear solid state NMR and XPS approach, including 133Cs-1H heteronuclear correlation 2D (HETCOR) NMR, was utilised to study the nanocrystal surface and ligands, demonstrating that the surface is Cs-Br rich with vacancies passivated by didodecyldimethylammonium bromide (DDAB) ligands. Furthermore, it is shown that a negligible amount of phosphonate ligands remain on the powder nanocrystal surface, despite the key role of octylphosphonic acid (OPA) in controlling the colloidal nanocrystal growth. The CsPbBr3 NCs were shown to be structurally stable under ambient conditions for up to 6 months, albeit with some particle agglomeration.