Regulation of Collective Metastasis by Nanolumenal Signaling.

Collective metastasis is defined as the cohesive migration and metastasis of multicellular tumor cell clusters. Disrupting various cell adhesion genes markedly reduces cluster formation and colonization efficiency, yet the downstream signals transmitted by clustering remain largely unknown. Here, we use mouse and human breast cancer models to identify a collective signal generated by tumor cell clusters supporting metastatic colonization. We show that tumor cell clusters produce the growth factor epigen and concentrate it within nanolumina-intercellular compartments sealed by cell-cell junctions and lined with microvilli-like protrusions. Epigen knockdown profoundly reduces metastatic outgrowth and switches clusters from a proliferative to a collective migratory state. Tumor cell clusters from basal-like 2, but not mesenchymal-like, triple-negative breast cancer cell lines have increased epigen expression, sealed nanolumina, and impaired outgrowth upon nanolumenal junction disruption. We propose that nanolumenal signaling could offer a therapeutic target for aggressive metastatic breast cancers.

Collective invasion in breast cancer requires a conserved basal epithelial program.

Carcinomas typically invade as a cohesive multicellular unit, a process termed collective invasion. It remains unclear how different subpopulations of cancer cells contribute to this process. We developed three-dimensional (3D) organoid assays to identify the most invasive cancer cells in primary breast tumors. Collective invasion was led by specialized cancer cells that were defined by their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63. Furthermore, K14+ cells led collective invasion in the major human breast cancer subtypes. Importantly, luminal cancer cells were observed to convert phenotypically to invasive leaders following induction of basal epithelial genes. Although only a minority of cells within luminal tumors expressed basal epithelial genes, knockdown of either K14 or p63 was sufficient to block collective invasion. Our data reveal that heterotypic interactions between epithelial subpopulations are critical to collective invasion. We suggest that targeting the basal invasive program could limit metastatic progression.

Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7.

Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core.

Probing the Architecture of Multisubunit Protein Complexes with In-line Disulfide Reduction and Native MS Analysis.

Native mass spectrometry (MS) continues to enjoy growing popularity as a means of providing a wealth of information on noncovalent biopolymer assemblies ranging from composition and binding stoichiometry to characterization of the topology of these assemblies. The latter frequently relies on supplementing MS measurements with limited fragmentation of the noncovalent complexes in the gas phase to identify the pairs of neighboring subunits. While this approach has met with much success in the past two decades, its implementation remains difficult (and the success record relatively modest) within one class of noncovalent assemblies: protein complexes in which at least one binding partner has multiple subunits cross-linked by disulfide bonds. We approach this problem by inducing chemical reduction of disulfide bonds under nondenaturing conditions in solution followed by native MS analysis with online buffer exchange to remove unconsumed reagents that are incompatible with the electrospray ionization process. While this approach works well with systems comprised of thiol-linked subunits that remain stable upon reduction of the disulfide bridges (such as immunoglobulins), chemical reduction frequently gives rise to species that are unstable (prone to aggregation). This problem is circumvented by taking advantage of the recently introduced cross-path reactive chromatography platform (XPRC), which allows the disulfide reduction to be carried out in-line, thereby minimizing the loss of metastable protein subunits and their noncovalent complexes with the binding partners prior to MS analysis. The feasibility of this approach is demonstrated using hemoglobin complexes with haptoglobin 1-1, a glycoprotein consisting of four polypeptide chains cross-linked by disulfide bonds.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Maternal Morbidity with Repeated Cesarean Deliveries.

OBJECTIVE: This study aimed to estimate the association between adverse maternal outcomes and the number of repeated cesarean deliveries (CDs) in a single obstetrical practice. STUDY DESIGN: Retrospective cohort study of all CDs between 2005 and 2020 in a single maternal fetal medicine practice. We used electronic records to get baseline characteristics and pregnancy/surgical outcomes based on the number of prior CDs. We performed two subgroup analyses for women with and without placenta previa. Chi-square for trend and one-way analysis of variance (ANOVA) were used. RESULTS: A total of 3,582 women underwent CD and met inclusion criteria. Of these women, 1,852 (51.7%) underwent their first cesarean, 950 (26.5%) their second, 382 (10.7%) their third, 191 (5.3%) their fourth, 117 (3.3%) their fifth, and 84 (2.3%) their sixth or higher CDs. The incidence of adverse outcomes (placenta accreta, uterine window, uterine rupture, hysterectomy, blood transfusion, cystotomy, bowel injury, need for a ventilator postpartum, intensive care unit admission, wound complications, thrombosis, reoperation, and maternal death) increased with additional CDs. However, the absolute rates remained low. In women without a placenta previa, the likelihood of adverse outcome did not differ across groups. In women with a placenta previa, adverse outcomes increased with increasing CDs. However, the incidence of placenta previa did not increase with increasing CDs (<5% in each group). The incidence of a uterine dehiscence increased significantly with additional CDs: first, 0.2%; second, 2.0%; third, 6.6%; fourth, 10.3%; fifth, 5.8%; and sixth or higher, 10.4% (p < 0.001). CONCLUSION: Maternal morbidity increases with CDs, but the absolute risks remain low. For women without placenta previa, increasing CDs is not associated with maternal morbidity. For women with placenta previa, risks are highest, but the incidence of placenta previa does not increase with successive CDs. The likelihood of uterine dehiscence increases significantly with increasing CDs which should be considered when deciding about timing of delivery in this population. KEY POINTS: · Maternal morbidity increase with each CD.. · Absolute adverse outcomes remains low in highest order CDs.. · In women without placenta previa, there is no added morbidity with additional CDs..

Automated Implementation of the Edinburgh Visual Gait Score (EVGS) Using OpenPose and Handheld Smartphone Video.

Recent advancements in computing and artificial intelligence (AI) make it possible to quantitatively evaluate human movement using digital video, thereby opening the possibility of more accessible gait analysis. The Edinburgh Visual Gait Score (EVGS) is an effective tool for observational gait analysis, but human scoring of videos can take over 20 min and requires experienced observers. This research developed an algorithmic implementation of the EVGS from handheld smartphone video to enable automatic scoring. Participant walking was video recorded at 60 Hz using a smartphone, and body keypoints were identified using the OpenPose BODY25 pose estimation model. An algorithm was developed to identify foot events and strides, and EVGS parameters were determined at relevant gait events. Stride detection was accurate within two to five frames. The level of agreement between the algorithmic and human reviewer EVGS results was strong for 14 of 17 parameters, and the algorithmic EVGS results were highly correlated (r > 0.80, "r" represents the Pearson correlation coefficient) to the ground truth values for 8 of the 17 parameters. This approach could make gait analysis more accessible and cost-effective, particularly in areas without gait assessment expertise. These findings pave the way for future studies to explore the use of smartphone video and AI algorithms in remote gait analysis.

Hands-On Workshops Improve Emergency Department Physicians' Self-Reported Understanding of Pediatric Hand Injuries.

OBJECTIVES: The aims of this study were to assess emergency department (ED) physician perception of hand injuries and improve their understanding and confidence in treating these injuries. METHODS: Combined didactic and hands-on workshops for ED physicians were developed and run by a team of medical students, plastic surgeons, and ED physicians. The workshops consisted of a short review by a hand surgeon followed by hands-on sessions involving radiograph assessment, administration of local anesthetic, closed reduction, and splinting. Two sessions, 6 months apart, were provided. The workshops were evaluated using preworkshop and postworkshop questionnaires to assess the following domains: confidence and competence in treating hand injuries, knowledge of basic hand injury care, and feedback on the intervention itself. RESULTS: Fifty physicians participated in the workshops. After the workshops, physician recognition of hand fracture reduction as a critical skill increased. Self-efficacy ratings of fracture assessment, administration of local anesthetic, performing a reduction, and applying postreduction immobilization increased. Median scores on knowledge-testing questions also increased postintervention from 73.3% (95% confidence interval, 70.2-78.5) to 86.7% (95% confidence interval, 79.3-86.2) (P < 0.05). Finally, physicians reported that they found the intervention educational, useful, and important, and approximately 90% of participants indicated they intended to change their practice based on this intervention. CONCLUSIONS: Knowledge sharing between specialists and generalists through combined didactic and hands-on workshops is an effective and well-received method of refining physician knowledge and increasing confidence in treating subspecialty-specific clinical presentations.

Predictors of Radial to Femoral Artery Access Crossover During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Radial access for primary percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) is associated with reduced mortality and bleeding, when compared to femoral access. However, radial access failure may be associated with an increased door-to-device (DTD) time. AIMS: To identify predictors of radial access failure requiring crossover to femoral artery access during primary PCI. METHODS: From 2013 to 2020, 2,256 consecutive patients treated for PPCI at a single tertiary hospital were prospectively recruited into the Victorian Cardiac Outcomes Registry and followed for 30 days. Multivariable logistic regression was used to identify independent predictors of radial to femoral access crossover. RESULTS: From 2,256 STEMI patients, primary radial access was used in 1,778 (78.8%), with 171 (9.6%) experiencing radial-to-femoral crossover. Patients with failed versus successful radial access experienced longer DTD times (67 mins, interquartile range [IQR] 46-99 vs 54 mins [IQR 39-78]; p<0.001). Independent predictors of radial-to-femoral access crossover included female sex (Adjusted Odds Ratio [AOR] 2.1, 95% Confidence Interval [CI] 1.4-3.0; p<0.001) and baseline hypertension (AOR 1.5, 95% CI 1.1-2.1; p=0.018). CONCLUSION: In a real-world STEMI registry, almost 1 in 10 patients experienced access crossover from the radial to femoral artery which resulted in longer DTD times. Independent predictors of radial access failure included female sex and baseline hypertension. Knowing which patient characteristics are associated with increased risk of radial artery failure enables catheter laboratory staff to ensure equipment is readily available to maximise successful primary PCI are available.

Analyzing the Administrative Burden of Competency Based Medical Education.

PURPOSE: Postgraduate residency programs in Canada are transitioning to a competency-based medical education (CBME) system. Within this system, resident performance is documented through frequent assessments that provide continual feedback and guidance for resident progression. An area of concern is the perception by faculty of added administrative burden imposed by the frequent evaluations. This study investigated the time spent in the documentation and submission of required assessment forms through analysis of quantitative data from the Queen's University Diagnostic Radiology program. METHODS AND MATERIALS: Data regarding time taken to complete Entrustable Professional Activities (EPA) assessments was collected from 24 full-time and part-time radiologists over a period of 18 months. This data was analyzed using SPSS to determine mean time of completion by individuals, departments, and by experience with the assessment process. RESULTS: The average time taken to complete an EPA assessment form was 3 minutes and 6 seconds. Assuming 3 completed EPA assessment forms per week for each resident (n = 12) and equal distribution among all staff, this averaged out to an additional 18 minutes of administrative burden per staff member over a 4 week block. CONCLUSIONS: This study investigated the perception by faculty of additional administrative burden for assessment in the CBME framework. The data provided quantitative evidence of administrative burden for the documentation and submission of assessments. The data indicated that the added administrative burden may be reasonable given mandate for CBME implementation and the advantages of adoption for postgraduate medical education.

Between-tumor and within-tumor heterogeneity in invasive potential.

For women with access to healthcare and early detection, breast cancer deaths are caused primarily by metastasis rather than growth of the primary tumor. Metastasis has been difficult to study because it happens deep in the body, occurs over years, and involves a small fraction of cells from the primary tumor. Furthermore, within-tumor heterogeneity relevant to metastasis can also lead to therapy failures and is obscured by studies of bulk tissue. Here we exploit heterogeneity to identify molecular mechanisms of metastasis. We use "organoids", groups of hundreds of tumor cells taken from a patient and grown in the lab, to probe tumor heterogeneity, with potentially thousands of organoids generated from a single tumor. We show that organoids have the character of biological replicates: within-tumor and between-tumor variation are of similar magnitude. We develop new methods based on population genetics and variance components models to build between-tumor and within-tumor statistical tests, using organoids analogously to large sibships and vastly amplifying the test power. We show great efficiency for tests based on the organoids with the most extreme phenotypes and potential cost savings from pooled tests of the extreme tails, with organoids generated from hundreds of tumors having power predicted to be similar to bulk tests of hundreds of thousands of tumors. We apply these methods to an association test for molecular correlates of invasion, using a novel quantitative invasion phenotype calculated as the spectral power of the organoid boundary. These new approaches combine to show a strong association between invasion and protein expression of Keratin 14, a known biomarker for poor prognosis, with p = 2 × 10-45 for within-tumor tests of individual organoids and p < 10-6 for pooled tests of extreme tails. Future studies using these methods could lead to discoveries of new classes of cancer targets and development of corresponding therapeutics. All data and methods are available under an open source license at https://github.com/baderzone/invasion_2019.

Intrinsic peripheral nerve and root tumor and pseudotumoral lesions at a tertiary care pediatric hospital.

PURPOSE: Tumors affecting peripheral nerves in children are rare. Accurate diagnosis ensures that management is appropriate and timely. A review of intrinsic nerve tumors was completed to differentiate common peripheral nerve lesions based on clinical characteristics and investigations. METHODS: A retrospective review was conducted for children (< 18 years old) diagnosed with an intrinsic tumor affecting peripheral nerve(s) or roots at the Children's Hospital of Eastern Ontario (CHEO) from 2009 to 2019. RESULTS: We report 14 children with perineurioma (N = 6), neurofibroma (N = 4), intraneural ganglion cyst (N = 2), or lipomatosis (N = 2). Mean age of symptom onset was 8.2 years (range 0.3 to 17.3 years). Presenting symptoms included muscle weakness (7/14), painless muscle wasting (2/14), contracture (1/14), pain (1/14), or the identification of a painless mass (3/14). Nerve conduction studies (NCS) or electromyography (EMG) were performed in 11/14 patients. MRI was useful at differentiating between these pediatric nerve tumors. Biopsies were performed in nine patients with additional surgical management pursued in four patients. CONCLUSION: The rare nature of peripheral nerve tumors in children can pose diagnostic challenges. NCS/EMG are important to assist with localization, and MRI is useful to distinguish more benign tumors. Key MRI, clinical, and NCS features can in some cases guide management, potentially avoiding the need for invasive procedures.

Activation of orexin system facilitates anesthesia emergence and pain control.

Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by designer drugs (DREADD) chemogenetic approach. With injection of adeno-associated virus into the orexin-Cre transgenic mouse brain, we expressed the DREADD receptor hM3Dq specifically in orexin neurons and applied the hM3Dq ligand clozapine to activate orexin neurons. We monitored orexin neuronal activities by c-Fos staining and whole-cell patch-clamp recording and examined the consequence of orexin neuronal activation via EEG recording. Our results revealed that the orexin-DREADD mice with activated orexin neurons emerged from anesthesia with significantly shorter latency than the control mice. As an indication of reduced pain sensitivity, these orexin-DREADD mice took longer to respond to the 55 °C thermal stimuli in the hot plate test and exhibited significantly less frequent licking of the formalin-injected paw in the formalin test. Our study suggests that approaches to activate the orexin system can be beneficial in postoperative recovery.

Detecting DNA and RNA and Differentiating Single-Nucleotide Variations via Field-Effect Transistors.

We detect short oligonucleotides and distinguish between sequences that differ by a single base, using label-free, electronic field-effect transistors (FETs). Our sensing platform utilizes ultrathin-film indium oxide FETs chemically functionalized with single-stranded DNA (ssDNA). The ssDNA-functionalized semiconducting channels in FETs detect fully complementary DNA sequences and differentiate these sequences from those having different types and locations of single base-pair mismatches. Changes in charge associated with surface-bound ssDNA vs double-stranded DNA (dsDNA) alter FET channel conductance to enable detection due to differences in DNA duplex stability. We illustrate the capability of ssDNA-FETs to detect complementary RNA sequences and to distinguish from RNA sequences with single nucleotide variations. The development and implementation of electronic biosensors that rapidly and sensitively detect and differentiate oligonucleotides present new opportunities in the fields of disease diagnostics and precision medicine.

Differential Charging in Photoemission from Mercurated DNA Monolayers on Ferromagnetic Films.

Spin-dependent and enantioselective electron-molecule scattering occurs in photoelectron transmission through chiral molecular films. This spin selectivity leads to electron spin filtering by molecular helices, with increasing magnitude concomitant with increasing numbers of helical turns. Using ultraviolet photoelectron spectroscopy, we measured spin-selective surface charging accompanying photoemission from ferromagnetic substrates functionalized with monolayers of mercurated DNA hairpins that constitute only one helical turn. Mercury ions bind specifically at thymine-thymine mismatches within self-hybridized single-stranded DNA, enabling precise control over the number and position of Hg2+ along the helical axis. Differential charging of the organic layers, manifested as substrate-magnetization-dependent photoionization energies, was observed for DNA hairpins containing Hg2+; no differences were measured for hairpin monolayers in the absence of Hg2+. Inversion of the DNA helical secondary structure at increased metal loading led to complementary inversion in spin selectivity. We attribute these results to increased scattering probabilities from relativistic enhancement of spin-orbit interactions in mercurated DNA.

Optimal, Large-Scale Propagation of Mouse Mammary Tumor Organoids.

Tumor organoids mimic the architecture and heterogeneity of in vivo tumors and enable studies of collective interactions between tumor cells as well as with their surrounding microenvironment. Although tumor organoids hold significant promise as cancer models, they are also more costly and labor-intensive to cultivate than traditional 2D cell culture. We sought to identify critical factors regulating organoid growth ex vivo, and to use these observations to develop a more efficient organoid expansion method. Using time-lapse imaging of mouse mammary tumor organoids in 3D culture, we observed that outgrowth potential varies non-linearly with initial organoid size. Maximal outgrowth occurred in organoids with a starting size between ~10 to 1000 cells. Based on these observations, we developed a suspension culture method that maintains organoids in the ideal size range, enabling expansion from 1 million to over 100 million cells in less than 2 weeks and less than 3 hours of hands-on time. Our method facilitates the rapid, cost-effective expansion of organoids for CRISPR based studies and other assays requiring a large amount of organoid starting material.

Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear. Purpose: To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults. Data Sources: EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles. Study Selection: Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments. Data Synthesis: Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes. Limitation: Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement. Conclusion: The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Effect of Lower Versus Higher Red Meat Intake on Cardiometabolic and Cancer Outcomes: A Systematic Review of Randomized Trials.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Few randomized trials have evaluated the effect of reducing red meat intake on clinically important outcomes. Purpose: To summarize the effect of lower versus higher red meat intake on the incidence of cardiometabolic and cancer outcomes in adults. Data Sources: EMBASE, CENTRAL, CINAHL, Web of Science, and ProQuest from inception to July 2018 and MEDLINE from inception to April 2019, without language restrictions. Study Selection: Randomized trials (published in any language) comparing diets lower in red meat with diets higher in red meat that differed by a gradient of at least 1 serving per week for 6 months or more. Data Extraction: Teams of 2 reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. Data Synthesis: Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality (hazard ratio [HR], 0.99 [95% CI, 0.95 to 1.03]), cardiovascular mortality (HR, 0.98 [CI, 0.91 to 1.06]), and cardiovascular disease (HR, 0.99 [CI, 0.94 to 1.05]). That trial also provided low- to very-low-certainty evidence that diets lower in red meat may have little or no effect on total cancer mortality (HR, 0.95 [CI, 0.89 to 1.01]) and the incidence of cancer, including colorectal cancer (HR, 1.04 [CI, 0.90 to 1.20]) and breast cancer (HR, 0.97 [0.90 to 1.04]). Limitations: There were few trials, most addressing only surrogate outcomes, with heterogeneous comparators and small gradients in red meat consumption between lower versus higher intake groups. Conclusion: Low- to very-low-certainty evidence suggests that diets restricted in red meat may have little or no effect on major cardiometabolic outcomes and cancer mortality and incidence. Primary Funding Source: None (PROSPERO: CRD42017074074).

Synchronization of extreme rainfall during the Australian summer monsoon: Complex network perspectives.

Monsoon rains are an important fresh water supply for agricultural activity, while extreme rainfalls during a monsoon season frequently cause flash floods. In this study, a nonlinear causation measure of event synchronization is used to set complex networks of extreme rainfall during the Australian summer monsoon (ASM) development between 1st November and 1st March. We adopted Tropical Rainfall Measuring Mission-based satellite rain rate estimates from 1998 to 2015. Examining several standard network centrality measures, such as degree and local clustering, we revealed the multiscale nature of ASM development, which previously was only studied by weather analysis methods. The land-sea contrast in surface heating critical for ASM is depicted clearly by the degree centrality. In addition, both the clustering coefficient and the community structure show critical change in spatial pattern matching with the climatological average onset time of the ASM during late December. The former is likely related to the interaction between synoptic forcing and mesoscale convection during monsoon onset, resulting in characteristic changes in the rainfall field. One of the network communities also extends spatially during the onset, revealing critical information from the near-equatorial region to ASM and would be applicable to monitor monsoon development. Results from this study further support that network measures as defined by a single parameter of rainfall have enormous potential for monsoon onset prediction.

Fibroadipose Vascular Anomaly in the Upper Extremity: A Distinct Entity With Characteristic Clinical, Radiological, and Histopathological Findings.

PURPOSE: Fibroadipose vascular anomaly (FAVA) is an intramuscular vascular malformation that has been recently described as a distinct clinical entity. The clinical, radiological, and histopathological characteristics of FAVA in the upper extremity are reviewed. METHODS: This was a retrospective case series of upper-extremity FAVA lesions. RESULTS: We reviewed 19 patients with FAVA of the upper limb. Pain, stiffness, swelling, and flexion contractures were the most common presentations. Except for one lesion confined to the hand, all lesions either presented with or developed a contracture within 10 years. Ten patients underwent surgical debulking. Six required tendon transfer reconstruction and 3 necessitated a free functional muscle transfer. CONCLUSIONS: Fibroadipose vascular anomaly in the upper extremity requires an accurate diagnosis and may benefit from early referral to a multidisciplinary vascular anomaly center with experienced hand surgeons. Compression garments, propranolol, and sclerotherapy seem to be ineffective. Surgical resection focused on symptomatic regions with appropriate reconstruction may have benefit in salvage of limbs with compromised function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.