Defining Cervical Sagittal Plane Deformity – When Are Sagittal Realignment Procedures Necessary in Patients Presenting Primarily With Radiculopathy or Myelopathy?

Objective It remains unclear whether cervical sagittal deformity (CSD) should be defined by radiographic parameters alone versus both clinical and radiographic factors, and whether radiographic malalignment by itself warrants a CSD corrective surgery in patients who present primarily with neurologic symptoms. Methods We administered a survey to a group of expert surgeons to evaluate whether radiographic parameters alone were sufficient to diagnose CSD, and in which scenarios surgeons recommend a CSD realignment procedure versus addressing the neurologic symptoms alone. Results No single radiographic criteria reached a 50% threshold as being sufficient to establish the diagnosis of CSD. When asymptomatic radiographic malalignment was present, a sagittal deformity correction was more likely to be recommended in patients with myelopathy versus those with radiculopathy alone. The majority of surgeons recommended deformity correction when symptoms of cervical deformity were present in addition to radiographic malalignment (85% with deformity symptoms and radiculopathy, 93% with deformity symptoms and myelopathy). Conclusion There is no consensus on which radiographic and/or clinical criteria are necessary to define the presence of CSD. We recommend that symptoms of cervical deformity, in addition to radiographic parameters, be considered when deciding whether to perform deformity correction in patients who present primarily with myelopathy or radiculopathy

Chaste : Cancer, Heart and Soft Tissue Environment

Funding: UK Engineering and Physical Sciences Research Council [grant number EP/N509711/1 (J.K.)].Chaste (Cancer, Heart And Soft Tissue Environment) is an open source simulation package for the numerical solution of mathematical models arising in physiology and biology. To date, Chaste development has been driven primarily by applications that include continuum modelling of cardiac electrophysiology (‘Cardiac Chaste’), discrete cell-based modelling of soft tissues (‘Cell-based Chaste’), and modelling of ventilation in lungs (‘Lung Chaste’). Cardiac Chaste addresses the need for a high-performance, generic, and verified simulation framewor kfor cardiac electrophysiology that is freely available to the scientific community. Cardiac chaste provides a software package capable of realistic heart simulations that is efficient, rigorously tested, and runs on HPC platforms. Cell-based Chaste addresses the need for efficient and verified implementations of cell-based modelling frameworks, providing a set of extensible tools for simulating biological tissues. Computational modelling, along with live imaging techniques, plays an important role in understanding the processes of tissue growth and repair. A wide range of cell-based modelling frameworks have been developed that have each been successfully applied in a range of biological applications. Cell-based Chaste includes implementations of the cellular automaton model, the cellular Potts model, cell-centre models with cell representations as overlapping spheres or Voronoi tessellations, and the vertex model. Lung Chaste addresses the need for a novel, generic and efficient lung modelling software package that is both tested and verified. It aims to couple biophysically-detailed models of airway mechanics with organ-scale ventilation models in a package that is freely available to the scientific community.Publisher PDFPeer reviewe

The Impact of COVID-19 Pandemic on Spine Surgeons Worldwide : A One Year Prospective Comparative Study

Study Design: Survey Objective: In March of 2020, an original study by Louie et al investigated the impact of COVID-19 on 902 spine surgeons internationally. Since then, due to varying government responses and public health initiatives to the pandemic, individual countries and regions of the world have been affected differently. Therefore, this follow-up study aimed to assess how the COVID-19 impact on spine surgeons has changed 1 year later. Methods: A repeat, multi-dimensional, 90-item survey written in English was distributed to spine surgeons worldwide via email to the AO Spine membership who agreed to receive surveys. Questions were categorized into the following domains: demographics, COVID-19 observations, preparedness, personal impact, patient care, and future perceptions. Results: Basic respondent demographics, such as gender, age, home demographics, medical comorbidities, practice type, and years since training completion, were similar to those of the original 2020 survey. Significant differences between groups included reasons for COVID testing, opinions of media coverage, hospital unemployment, likelihood to be performing elective surgery, percentage of cases cancelled, percentage of personal income, sick leave, personal time allocation, stress coping mechanisms, and the belief that future guidelines were needed (P<.05). Conclusion: Compared to baseline results collected at the beginning of the COVID-19 pandemic in 2020, significant differences in various domains related to COVID-19 perceptions, hospital preparedness, practice impact, personal impact, and future perceptions have developed. Follow-up assessment of spine surgeons has further indicated that telemedicine and virtual education are mainstays. Such findings may help to inform and manage expectations and responses to any future outbreaks.publishedVersionPeer reviewe

Perioperative Anticoagulation Management in Spine Surgery: Initial Findings From the AO Spine Anticoagulation Global Survey.

STUDY DESIGN: Cross-sectional, international survey. OBJECTIVES: This study addressed the global perspectives concerning perioperative use of pharmacologic thromboprophylaxis during spine surgery along with its risks and benefits. METHODS: A questionnaire was designed and implemented by expert members in the AO Spine community. The survey was distributed to AO Spine\u27s spine surgeon members (N = 3805). Data included surgeon demographic information, type and region of practice, anticoagulation principles, different patient scenarios, and comorbidities. Results: A total of 316 (8.3% response rate) spine surgeons completed the survey, representing 64 different countries. Completed surveys were primarily from Europe (31.7%), South/Latin America (19.9%), and Asia (18.4%). Surgeons tended to be 35 to 44 years old (42.1%), fellowship-trained (74.7%), and orthopedic surgeons (65.5%) from academic institutions (39.6%). Most surgeons (70.3%) used routine anticoagulation risk stratification, irrespective of geographic location. However, significant differences were seen between continents with anticoagulation initiation and cessation methodology. Specifically, the length of a procedure (P = .036) and patient body mass index (P = .008) were perceived differently when deciding to begin anticoagulation, while the importance of medical clearance (P \u3c .001) and reference to literature (P = .035) differed during cessation. For specific techniques, most providers noted use of mobilization, low-molecular-weight heparin, and mechanical prophylaxis beginning on postoperative 0 to 1 days. Conversely, bridging regimens were bimodal in distribution, with providers electing anticoagulant initiation on postoperative 0 to 1 days or days 5-6. CONCLUSION: This survey highlights the heterogeneity of spine care and accentuates geographical variations. Furthermore, it identifies the difficulty in providing consistent perioperative anticoagulation recommendations to patients, as there remains no widely accepted, definitive literature of evidence or guidelines

Factors Affecting the Decision to Initiate Anticoagulation After Spine Surgery: Findings From the AOSpine Anticoagulation Global Initiative

STUDY DESIGN: Cross-sectional, international survey. OBJECTIVES: To identify factors influencing pharmacologic anticoagulation initiation after spine surgery based on the AOSpine Anticoagulation Global Survey. METHODS: This survey was distributed to the international membership of AOSpine (n = 3805). A Likert-type scale described grade practice-specific factors on a scale from low (1) to high (5) importance, and patient-specific factors a scale from low (0) to high (3) importance. Analysis was performed to determine which factors were significant in the decision making surrounding the initiation of pharmacologic anticoagulation. RESULTS: A total of 316 spine surgeons from 64 countries completed the survey. In terms of practice-specific factors considered to initiate treatment, expert opinion was graded the highest (mean grade ± SD = 3.2 ± 1.3), followed by fellowship training (3.2 ± 1.3). Conversely, previous studies (2.7 ± 1.2) and unspecified guidelines were considered least important (2.6 ± 1.6). Patient body mass index (2.0 ± 1.0) and postoperative mobilization (2.3 ± 1.0) were deemed most important and graded highly overall. Those who rated estimated blood loss with greater importance in anticoagulation initiation decision making were more likely to administer thromboprophylaxis at later times (hazard ratio [HR] = 0.68-0.71), while those who rated drain output with greater importance were likely to administer thromboprophylaxis at earlier times (HR = 1.32-1.43). CONCLUSION: Among our global cohort of spine surgeons, certain patient factors (ie, patient mobilization and body mass index) and practice-specific factors (ie, expert opinion and fellowship training) were considered to be most important when considering anticoagulation start times

Reinterpretation of LHC Results for New Physics: Status and recommendations after Run 2

We report on the status of efforts to improve the reinterpretation of searches and measurements at the LHC in terms of models for new physics, in the context of the LHC Reinterpretation Forum. We detail current experimental offerings in direct searches for new particles, measurements, technical implementations and Open Data, and provide a set of recommendations for further improving the presentation of LHC results in order to better enable reinterpretation in the future. We also provide a brief description of existing software reinterpretation frameworks and recent global analyses of new physics that make use of the current data

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Spike-Based Bayesian-Hebbian Learning of Temporal Sequences

Many cognitive and motor functions are enabled by the temporal representation and processing of stimuli, but it remains an open issue how neocortical microcircuits can reliably encode and replay such sequences of information. To better understand this, a modular attractor memory network is proposed in which meta-stable sequential attractor transitions are learned through changes to synaptic weights and intrinsic excitabilities via the spike-based Bayesian Confidence Propagation Neural Network (BCPNN) learning rule. We find that the formation of distributed memories, embodied by increased periods of firing in pools of excitatory neurons, together with asymmetrical associations between these distinct network states, can be acquired through plasticity. The model's feasibility is demonstrated using simulations of adaptive exponential integrate-and-fire model neurons (AdEx). We show that the learning and speed of sequence replay depends on a confluence of biophysically relevant parameters including stimulus duration, level of background noise, ratio of synaptic currents, and strengths of short-term depression and adaptation. Moreover, sequence elements are shown to flexibly participate multiple times in the sequence, suggesting that spiking attractor networks of this type can support an efficient combinatorial code. The model provides a principled approach towards understanding how multiple interacting plasticity mechanisms can coordinate hetero-associative learning in unison