Molecular Machines from Topological Linkages

Life is built upon amazingly sophisticated molecular machines whose behavior combines mechanical and chemical action. Engineering of similarly complex nanoscale devices from first principles remains an as yet unrealized goal of bioengineering. In this paper we formalize a simple model of mechanical motion (mechanical linkages) combined with chemical bonding. The model has a natural implementation using DNA with double-stranded rigid links, and single-stranded flexible joints and binding sites. Surprisingly, we show that much of the complex behavior is preserved in an idealized topological model which considers solely the graph connectivity of the linkages. We show a number of artifacts including Boolean logic, catalysts, a fueled motor, and chemo-mechanical coupling, all of which can be understood and reasoned about in the topological model. The variety of achieved behaviors supports the use of topological chemical linkages in understanding and engineering complex molecular behaviors

Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: a meta-analysis

BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Mandibular distraction osteogenesis in the management of airway obstruction in children with micrognathia: a systematic review

Background Mandibular distraction osteogenesis (MDO) is becoming increasingly commonly used as the primary surgical option for neonates and infants with upper airway obstruction secondary to micrognathia or to facilitate decannulation for tracheostomy dependent children. Objectives The objective of this review was to identify and synthesize the best available evidence on the effectiveness of MDO on airway patency, feeding, gastro-esophageal reflux (GORD) and long-term development in children born with upper airway obstruction secondary to micrognathia. This review also aims to determine the ideal rate of distraction, and compare outcomes of external and internal distractors in this patient group. Inclusion criteria The inclusion criterion included studies in children with clinical evidence of micrognathia/Pierre Robin Sequence (PRS) who have failed conservative treatments, including both syndromic (sMicro) and non-syndromic isolated PRS (iPRS) patients. The intervention is patients who have undergone bilateral distraction osteogenesis to prevent a tracheostomy or to facilitate decannulation. The comparator intervention is patients who underwent a tracheostomy alone. The outcomes of interest include relief of airway obstruction with MDO, decannulation of tracheostomy dependent patients, feeding and reflux changes, surgical outcomes such as comparison of rate of distraction and type of distractor. All study designs were included. Methods The databases searched included PubMed, Embase, Scopus, Web of Knowledge and grey literature sources. Of the 4815 studies found in the initial search, only 66 were included after critical appraisal. Due to the nature of the studies included, a meta-analysis was not possible. The data was pooled by calculating weighted means. Results Primary MDO for the relief of upper airway obstruction was successful in 95% of cases in the literature. Syndromic (sMicro) patients had odds of failure that were four times higher than those of iPRS patients. The most common causes of failure are previously undiagnosed lower airway obstruction, central apnoea, undiagnosed neurological abnormalities and complex multiorgan anomalies. Mandibular distraction osteogenesis (MDO) was less effective (80.3% success rate) at facilitating decannulation of tracheostomy dependent children. Failure in these patients was most commonly due to severe preoperative gastro-oesophageal reflux disease (GORD), swallowing dysfunction and tracheostomy related complications. The failure rate was higher when MDO was performed at an age of ≥24 months for this group of patients. Approximately 84% of children can be exclusively oral fed after MDO. The odds of needing feeding adjuncts were five times higher in syndromic children. There was a trend towards a growth decline in the first six weeks after surgery. MDO relieves GORD in the majority of patients. Patients who were tracheostomy dependent with severe GORD were at higher risk of failure to decannulate after MDO. There was no difference in success rate when comparing a distraction rate of 1mm/day with 2mm/day. External distractors were associated with a higher rate of failure and complications compared to internal distractors. Overall, there was a paucity of long-term results in the literature. Recurrence of airway distress may occur due to a relapse of retrognathia or TMJ ankylosis. Conclusion Mandibular distraction osteogenesis is an effective technique for preventing tracheostomy in children with airway obstruction secondary to micrognathia (Level 4 evidence). Thorough airway evaluation and sleep study pre-MDO is necessary to exclude multilevel airway obstruction and central apnoea. Mandibular distraction osteogenesis has a slightly lower success rate at facilitating decannulation. Thorough airway evaluation, assessment for reflux and swallowing dysfunction are necessary prior to surgery. Mandibular distraction osteogenesis is effective at alleviating feeding problems and reflux symptoms in these children. Care needs to be taken to avoid a general growth decline that has been reported in the first six weeks after surgery. Distracting at a rate of 1mm/day or 2mm/day below the age of 12 months is safe. Internal distractors have a higher success rate and a lower rate of complications than external distractors. More studies are needed to evaluate the long-term implications of MDO on facial development and long-term complications.Thesis (M.Clin.Sc.) -- University of Adelaide, School of Translational Health Science, 201

Chemical richness from abstract physical parts

Every living cell is a tiny, intricate chemical computer. But what aspects of chemistry can create that richness? This thesis explores and expands two abstract models of chemistry, binding networks and chemical linkages, and shows that despite their simplicity, they can exhibit complex behavior. A binding network is a minimal model driven by thermodynamics that treats a molecule as simply a bag of binding sites. We prove that natural questions about binding networks at thermodynamic equilibrium are computationally hard. To answer them quickly in practice, we develop algorithms and software that translate to boolean satisfiability. By introducing a kinetic framework, we then prove that binding networks allow catalysis, a powerful, inherently kinetic behavior. Chemical linkages add minimal geometric structure to binding networks using rods and joints. Out of chemical linkages, we construct ATP-like catalyzed splitting, a fueled motor, and chemo-mechanical coupling. We show that surprisingly, graph structure alone can explain the behavior of these machines. This provides a theoretical foundation toward understanding and mimicking the complexity of living systems.Computer Science

The Predictive Ability of Type D Personality Pattern, Anxiety, and Depression in Cardiac Disease

A growing body of empirical evidence suggests psychological and personality risk factors for cardiovascular disease in Western developed countries. This study expands that line of health research to a community sample of 309 Jordanians (half of whom were diagnosed with heart problems). Using the Distress Scale, Beck Depression Inventory-II, and State-Trait Anxiety Inventory, this study determined that Type D personality, depression, and anxiety have value in predicting cardiovascular disease. The results showed that older individuals with high levels of social inhibition are more likely to have heart disease compared to younger participants. Anxiety and depression were also potent risk factors. The emerging pattern confirms the cross-cultural validity of Type D personality as well as depression and anxiety indices in predisposing individuals to cardiovascular disease. This study calls for using a multiple-level-analysis approach combining personality and social influences. Patients and health providers can engineer health through psychological wellness and health-promotive behavior. Programs based on self-empowerment theory that target the roots of anxiety and depression, as well as the social inhibition and negative affectivity dimensions of Type D personality (e.g., rage, hostility), should be an integral component of any therapy or intervention