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The state of underwater networking today is similar to ARPANET back in the 1970s, when only a select few people with expensive hardware resources had access to the technology. We present the first acoustic system that brings underwater networking capabilities to existing mobile devices like smartphones and smart watches. Our software-only solution leverages audio sensors, i.e., microphones and speakers, ubiquitous in today's devices, to enable acoustic underwater communication between mobile devices. To achieve this, we design a communication system that adapts in real-time to differences in frequency responses across mobile devices, changes in multipath and noise levels at different locations and dynamic channel changes due to mobility. We evaluate our system in six different real-world underwater environments in the presence of boats, ships and people fishing and kayaking. With the release of Apple Watch Ultra that is specifically designed for underwater settings, our software-based approach has the potential to democratize underwater networking capabilities by making them widely available to anyone with a mobile device.

Otoacoustic emissions (OAEs) provide information about the function of the outer hair cells of the cochlea. In high-income countries, infants undergo OAE tests as part of the screening protocols for hearing. However, the cost of the necessary equipment hinders early screening for hearing in low- and middle-income countries, which disproportionately bear the brunt of disabling hearing loss. Here we report the design and clinical testing of a low-cost probe for OAEs. The device, which has a material cost of approximately US$10, uses an off-the-shelf microphone and off-the-shelf earphones connected to a smartphone through a headphone jack. It sends two pure tones through each of the headphone's earbuds and algorithmically detects the distortion-product OAEs generated by the cochlea and recorded via the microphone. In a clinical study involving 201 paediatric ears across three healthcare sites, the device detected hearing loss with 100% sensitivity and 88.9% specificity, comparable to the performance of a commercial device. Low-cost devices for OAE testing may aid the early detection of hearing loss in resource-constrained settings.

OBJECTIVE Experts can assess surgeon skill using surgical video, but a limited number of expert surgeons are available. Automated performance metrics (APMs) are a promising alternative but have not been created from operative videos in neurosurgery to date. The authors aimed to evaluate whether video-based APMs can predict task success and blood loss during endonasal endoscopic surgery in a validated cadaveric simulator of vascular injury of the internal carotid artery. METHODS Videos of cadaveric simulation trials by 73 neurosurgeons and otorhinolaryngologists were analyzed and manually annotated with bounding boxes to identify the surgical instruments in the frame. APMs in five domains were defined—instrument usage, time-to-phase, instrument disappearance, instrument movement, and instrument interactions—on the basis of expert analysis and task-specific surgical progressions. Bounding-box data of instrument position were then used to generate APMs for each trial. Multivariate linear regression was used to test for the associations between APMs and blood loss and task success (hemorrhage control in less than 5 minutes). The APMs of 93 successful trials were compared with the APMs of 49 unsuccessful trials. RESULTS In total, 29,151 frames of surgical video were annotated. Successful simulation trials had superior APMs in each domain, including proportionately more time spent with the key instruments in view (p < 0.001) and less time without hemorrhage control (p = 0.002). APMs in all domains improved in subsequent trials after the participants received personalized expert instruction. Attending surgeons had superior instrument usage, time-to-phase, and instrument disappearance metrics compared with resident surgeons (p < 0.01). APMs predicted surgeon performance better than surgeon training level or prior experience. A regression model that included APMs predicted blood loss with an R2 value of 0.87 (p < 0.001). CONCLUSIONS Video-based APMs were superior predictors of simulation trial success and blood loss than surgeon characteristics such as case volume and attending status. Surgeon educators can use APMs to assess competency, quantify performance, and provide actionable, structured feedback in order to improve patient outcomes. Validation of APMs provides a benchmark for further development of fully automated video assessment pipelines that utilize machine learning and computer vision.

Background: To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. Methods: Systematic review and meta-analysis following PRISMA guidelines Data sources: MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021. Study criteria: Phase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded. Data extraction: Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias. Results: 44 studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes. Conclusion: Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.

The initiation signals are raised around the promoter by one of the general transcription factors, triggering a sequence of events that lead to mRNA transcript formation from target genes. Both specific noncoding DNA regions and transacting, macromolecular assemblies are intricately involved and indispensable. The transition between the subsequent transcriptional stages is accompanied by stage-specific signals and structural changes in the macromolecular assemblies and facilitated by the recruitment/removal of other chromatin and transcription-associated elements. Here, we discuss the choreography of transacting factors around promoter in the establishment and effectuation of the initial phases of transcription such as NDR formation, +1 nucleosome positioning, promoter DNA opening, and RNAPII promoter escape from a structural viewpoint.

Amyloid fibrils formations are involved in many neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Amyotrophic Lateral Sclerosis (ALS) and others. The proteins associated with the formation of amyloid fibrils are Intrinsically Disordered Proteins (IDP) in the unbound state. Nevertheless, this type of proteins can self-aggregate and form cross-β amyloid fibrils structures at physiological condition.Due to the flexibility of these IDPs, no single experimental approach could completely characterize this system, especially in the unbound state. All-atom molecular dynamics (MD) simulations could be used to study the conformational ensemble of IDPs. Unfortunately, force fields (FF) and water models (WM) were developed to simulate one structure of folded proteins. Recently, several FF/WM were improved to properly generate conformational ensembles of IDP. However, it is unknown if the force fields (FF) can properly reproduce the behavior of IDP and also self-aggregate in cross-β amyloid fibrils structures.In this paper, we will focus of the R2 region of the FUS-LC domain (R2-FUS-LC region) which is an Intrinsically Disordered Region (IDR) of 16 residues in the unbound state but forms cross-β fibrils in the bound state. For the R2-FUS-LC region, we benchmarked thirteen commonly used FFs for studying IDPs. We show that CHARMM36m (updated in 2021) with mTIP3P water model performs the best to generate extended structures and cross-β amyloid fibril.

Neutrophil-to-lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus.This was a population-based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government-funded hospitals/clinics in Hong Kong. Follow-up was until 31 December, 2019, or death.A total of 85,351 patients (age = 67.6 ± 13.2 years old, male = 48.8%, follow-up = 3101 ± 1441 days) were included. Univariable Cox regression found that increased NLR at quartiles 2, 3 and 4 was significantly associated with higher risks of new-onset ischemic stroke (hazard ratio [HR]: 1.28 [1.20-1.37], p .001, HR: 1.41 [1.32-1.51], p .001 and HR: 1.38 [1.29-1.47], p .001) and AF (HR: 1.09 [1.02-1.17], p .015; HR: 1.28 [1.20-1.37], p .001; HR: 1.39 [1.31-1.49], p .001) compared to quartile 1. On multivariable analysis, NLR remained a significant predictor of ischemic stroke risk for quartiles 2 and 3 (quartile 2: HR: 1.14 [1.05, 1.22], p = .001; quartile 3: HR: 1.14 [1.06, 1.23], p .001) but not quartile 4 (HR: 1.08 [0.994, 1.17], p = .070). NLR was not predictive of AF after adjusting for confounders (quartile 2: HR: 0.966 [0.874, 1.07], p = .499; quartile 3: HR: 0.978 [0.884, 1.08], p = .661; quartile 4: HR: 1.05 [0.935, 1.16], p = .462).NLR is a significant predictor of new-onset ischaemic stroke after adjusting for significant confounders in Chinese type 2 diabetes patients.

The purpose of this review is to summarize recent literature on nontuberculous mycobacteria in water of healthcare systems. Despite improvement in identification techniques and emergence of infection prevention and control programs, nontuberculous mycobacteria remain present in hospital water systems, causing outbreaks and pseudo-outbreaks in healthcare settings.Waterborne outbreaks and pseudo-outbreaks of nontuberculous mycobacteria continue to affect hospitals. Improvements in methods of identification and investigation, including MALDI-TOF and whole genome sequencing with evaluation of single nucleotide polymorphisms, have been used successfully in outbreak and pseudo-outbreak investigations. Recent studies have shown control of outbreaks in immunocompromised patients through the use of sterile water for consumption, as well as control of pseudo-outbreaks by using sterile water for procedures. Construction activities have been implicated in outbreaks and pseudo-outbreaks of nontuberculous mycobacteria. Water management programs are now required by the Joint Commission, which will likely improve water risk mitigation.Improvement in detection and identification of nontuberculous mycobacteria has led to increasing recognition of waterborne outbreaks and pseudo-outbreaks. Water management programs are of vital importance in infection prevention.

Background: Emotional disclosure is the therapeutic expression of emotion. It holds potential as a means of providing psychological support. However, evidence of its efficacy in palliative settings is mixed. This may be due to variation in intervention characteristics. Aim: To derive a greater understanding of the characteristics of potentially effective emotional disclosure-based interventions in palliative care by: (1) Developing a taxonomy of emotional disclosure-based interventions tested in people with advanced disease and (2) Mapping and linking objectives, outcomes, underlying mechanisms, and implementation factors. Design: A scoping review drawing on Intervention Component Analysis to combine evidence from studies’ methods, results, and discussion sections. Data sources: Six databases were searched to May 2020 including CINAHL, PsycINFO, and MEDLINE. Studies of emotional disclosure in adults with advanced disease were included. Study quality was appraised using an established tool. Results: Seven thousand seven hundred ninety-two unique records were screened, of which 25 primary studies were included. Intervention characteristics were grouped into classes within three domains: topic of disclosure, format, and dose. Evidence was not available to determine which, if any, of the characteristics is most effective. Thematic synthesis of evidence from methods and discussion sections identified factors to consider in tailoring an emotional disclosure-based intervention to this setting, including: population characteristics (e.g. time since diagnosis), providing a safe environment, and flexibility in format. Conclusions: This review approach facilitated a clearer understanding of factors that may be key in developing emotional disclosure-based interventions for palliative populations. Intervention Component Analysis has potential for application elsewhere to help develop evidence-based interventions.

In this studies, synthesis of silver nanoparticles (Ag-NPs) on pullulan-based biofilm was achieved by microwave irradiation technique. Synthesis of Ag-NPs was achieved using pullulan as both a reducing and stabilizing agent. The effect of different microwave irradiation duration on pullulan and silver nitrate in synthesis of silver nanoparticles (Ag-NPs) was investigated. The synthesized Ag-NPs/PL were first screened and identified using surface plasmon peaks of UV–Vis spectroscopy. The research results indicated that the surface plasmon resonance peaks were observed between 400–414 nm wavelengths in UV-VIS spectroscopy studies. From Fourier-transform infrared spectroscopy (FTIR) spectra, stretching vibrations of hydroxyl (OH), carbonyl (C=O) and C=C stretches exhibits the reduction and stabilization of Ag-NPs. Further, five characteristic peaks Ag(111), Ag(200), Ag(210), Ag(220) and Ag(311) confirmed the presence of elemental silver and the crystalline structure of silver nanoparticles from X-ray Diffraction analysis. Biofilms were produced by mixing the synthesized Pulullan-Ag-NPs with polyvinyl alcohol. The AgNP/PL were applied for the antimicrobial activity against Bacillus subtilis and found to have high antibacterial activity. In addition, the clear zones of inhibition was found at 11 mm to 16 mm against Bacillus Subtillis. The experimental results demonstrated that pullulan could be used as reducing and stabilizing agent for formation of Ag-NPs.

Objectives People detained in correctional facilities are at high risk for infection with severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). We described the epidemiology of the COVID-19 outbreak in a large urban jail system, including signs and symptoms at time of testing and risk factors for hospitalization. Methods This retrospective observational cohort study included all patients aged ≥18 years who were tested for COVID-19 during March 11–April 28, 2020, while in custody in the New York City jail system (N = 978). We described demographic characteristics and signs and symptoms at the time of testing and performed Cox regression analysis to identify factors associated with hospitalization among those with a positive test result. Results Of 978 people tested for COVID-19, 568 received a positive test result. Among symptomatic patients, the most common symptoms among those who received a positive test result were cough (n = 293 of 510, 57%) and objective fever (n = 288 of 510, 56%). Of 257 asymptomatic patients who were tested, 58 (23%) received a positive test result. Forty-five (8%) people who received a positive test result were hospitalized for COVID-19. Older age (aged ≥55 vs 18-34) (adjusted hazard ratio [aHR] = 13.41; 95% CI, 3.80-47.33) and diabetes mellitus (aHR = 1.99; 95% CI, 1.00-3.95) were significantly associated with hospitalization. Conclusions A substantial proportion of people tested in New York City jails received a positive test result for COVID-19, including a large proportion of people tested while asymptomatic. During periods of ongoing transmission, asymptomatic screening should complement symptom-driven COVID-19 testing in correctional facilities. Older patients and people with diabetes mellitus should be closely monitored after COVID-19 diagnosis because of their increased risk for hospitalization.

Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO).A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO.In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

Background: Independent peer review of mortality cases has potential to identify issues in cardiothoracic surgical patients. The Australian and New Zealand Audit of Surgical Mortality aims to improve surgical care through peer-reviewed assessment of all surgical mortality. The aim of this study was to describe common clinical management issues that contribute to patient mortality in a cohort of Australian cardiothoracic surgical patients. This approach may subsequently provide a basis for quality improvement. Methods: Cardiothoracic mortality reports to the Australian and New Zealand Audit of Surgical Mortality from February 2009 through December 2015 were reviewed. The surgeon report and assessor comments were coded to identify clinical management issues. These were divided into perioperative stages (preoperative, intraoperative, and postoperative), and at each stage a thematic analysis was performed. Results: Of the 908 cases analyzed, 1371 clinical management issues were identified. Postoperative issues were the most common (n = 552), followed by preoperative (n = 378) and intraoperative issues (n = 370). Communication issues were present at all 3 stages (n = 71). Overall the most common theme was intraoperative technical issues (n = 287). Many of these issues revolved around unintentional injury to anatomic structures during surgery and inadequate myocardial protection. Communication issues commonly related to surgical handover to the intensive care unit and lack of shared decision-making. Also common were consultant surgeons being unaware of patient deterioration or significant changes in management. Conclusions: The Australian and New Zealand Audit of Surgical Mortality provides valuable insights into issues affecting mortality in cardiothoracic patients. Potentially avoidable management issues play a large role in determining the outcome of these patients. Quality improvement initiatives targeting these areas may be valuable. Refereed/Peer-reviewed

Jamestown Canyon virus (JCV) is a neuroinvasive arbovirus that is found throughout North America and increasingly recognized as a public health concern. From 2004 to 2012, an average of 1.7 confirmed cases were reported annually in the United States, whereas from 2013 to 2018 this figure increased over seventeen-fold to 29.2 cases per year. The rising number of reported human infections highlights the need for better understanding of the clinical manifestations and epidemiology of JCV. Here, we describe nine patients diagnosed with neuroinvasive JCV infection in Massachusetts from 2013, the year of the first reported case in the state, to 2017. Because current diagnostic testing relies on serology, which is complicated by cross-reactivity with related orthobunyaviruses and can be negative in immunosuppressed patients, we developed and evaluated an RT-qPCR assay for detection of JCV RNA. We tested this on the available archived serum from two patients, but did not detect viral RNA. JCV is transmitted by multiple mosquito species and its primary vector in Massachusetts is unknown, so we additionally applied the RT-qPCR assay and confirmatory RNA sequencing to assess JCV prevalence in a vector candidate, Ochlerotatus canadensis. We identified JCV in 0.6% of mosquito pools, a similar prevalence to neighboring Connecticut. We assembled the first Massachusetts JCV genome directly from a mosquito sample, finding high identity to JCV isolates collected over a 60-year period. Further studies are needed to reconcile the low vector prevalence and low rate of viral evolutionary change with the increasing number of reported cases.

Airway epithelial damage is a common feature in respiratory diseases such as COPD and has been suggested to drive inflammation and progression of disease. These features manifest as remodeling and destruction of lung epithelial characteristics including loss of small airways which contributes to chronic airway inflammation. Histone deacetylase 6 (HDAC6) has been shown to play a role in epithelial function and dysregulation, such as in cilia disassembly, epithelial to mesenchymal transition (EMT) and oxidative stress responses, and has been implicated in several diseases. We thus used ACY-1083, an inhibitor with high selectivity for HDAC6, and characterized its effects on epithelial function including epithelial disruption, cytokine production, remodeling, mucociliary clearance and cell characteristics.Primary lung epithelial air-liquid interface cultures from COPD patients were used and the impacts of TNF, TGF-β, cigarette smoke and bacterial challenges on epithelial function in the presence and absence of ACY-1083 were tested. Each challenge increased the permeability of the epithelial barrier whilst ACY-1083 blocked this effect and even decreased permeability in the absence of challenge. TNF was also shown to increase production of cytokines and mucins, with ACY-1083 reducing the effect. We observed that COPD-relevant stimulations created damage to the epithelium as seen on immunohistochemistry sections and that treatment with ACY-1083 maintained an intact cell layer and preserved mucociliary function. Interestingly, there was no direct effect on ciliary beat frequency or tight junction proteins indicating other mechanisms for the protected epithelium.In summary, ACY-1083 shows protection of the respiratory epithelium during COPD-relevant challenges which indicates a future potential to restore epithelial structure and function to halt disease progression in clinical practice.

The current understanding of how specific distributions of histone post-translational modifications (PTMs) are achieved throughout the chromatin remains incomplete. This review focuses on the role of RNA polymerase II (RNAPII) in establishing H2BK120/K123 ubiquitination and H3K4/K36 methylation distribution. The rate of RNAPII transcription is mainly a function of the RNAPII elongation and recruitment rates. Two major mechanisms link RNAPII's transcription rate to the distribution of PTMs. First, the phosphorylation patterns of Ser2P/Ser5P in the C-terminal domain of RNAPII change as a function of time, since the start of elongation, linking them to the elongation rate. Ser2P/Ser5P recruits specific histone PTM enzymes/activators to the nucleosome. Second, multiple rounds of binding and catalysis by the enzymes are required to establish higher methylations (H3K4/36me3). Thus, methylation states are determined by the transcription rate. In summary, the first mechanism determines the location of methylations in the gene, while the second mechanism determines the methylation state.

Background Tympanometry is used as part of a battery of tests for screening of middle ear function and may help diagnose middle ear disorders, but remains available only on expensive test equipment. Methods We report a low-cost smartphone-based tympanometer system that consists of a lightweight and portable attachment to vary air pressure in the ear and measure middle ear function. The smartphone displays a tympanogram and reports peak acoustic admittance in realtime. Our programmable and open-source system operates at 226 Hz and was tested on 50 pediatric patient ears in an audiology clinic in parallel with a commercial tympanometer. Results Our study shows an average agreement of 86 ± 2% between the 100 tympanograms produced by the smartphone and commercial device when five pediatric audiologists classified them into five classes based on the Liden and Jerger classification. Conclusion Given the accessibility and prevalence of budget smartphones in developing countries, our open-source tool may help provide timely and affordable screening of middle ear disorders.

Objective: Choledochal cysts (CCs) represent cystic dilatations of the intra- or extrahepatic biliary tract. The diagnosis of CCs may not always be straightforward particularly for the intrahepatic subtype. Whereas the gold standard for diagnosing CCs is endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP) is commonly used as primary diagnostic tool for delineation of biliary pathologies including CCs. Methods: We report a case of cystic hepatic lesion near the confluence of bilateral intrahepatic ducts. MRCP shows direct anatomical communication between the lesion and the biliary tract, raising suspicion of a CC. Endoscopic ultrasound shows no communication between the lesion and biliary system. 99mTc-hepatic iminodiacetic acid scintigraphy (hepatobiliary scintigraphy) was subsequently performed, showing no tracer uptake in the concerned cystic hepatic lesion despite visualisation of gallbladder and transit of tracer into the intestine. Overall scintigraphic findings speak against a CC. Conclusion: The case showed conflicting anatomical findings of a CC on MRCP and endoscopic ultrasound. Hepatobiliary scintigraphy and hepatobiliary contrast MRI may both functionally demonstrate communication of a hepatic lesion with the biliary tract. But hepatobiliary scintigraphy offers the advantage of much higher hepatic extraction and hence higher resistance to competition from plasma bilirubin compared with hepatobiliary contrast MRI. The better pharmacokinetics of HIDA confer superior lesion contrast that may offset inferior image spatial resolution, in particular for large lesions and patients with hyperbilirubinaemia. Hepatobiliary scintigraphy should be considered a suitable functional diagnostic modality for CCs even in the era of magnetic resonance imaging with cholangiopancreatography and contrast-enhanced hepatobiliary phase.

Intraoperative tool movement data have been demonstrated to be clinically useful in quantifying surgical performance. However, collecting this information from intraoperative video requires laborious hand annotation. The ability to automatically annotate tools in surgical video would advance surgical data science by eliminating a time-intensive step in research.To identify whether machine learning (ML) can automatically identify surgical instruments contained within neurosurgical video.A ML model which automatically identifies surgical instruments in frame was developed and trained on multiple publicly available surgical video data sets with instrument location annotations. A total of 39 693 frames from 4 data sets were used (endoscopic endonasal surgery [EEA] [30 015 frames], cataract surgery [4670], laparoscopic cholecystectomy [2532], and microscope-assisted brain/spine tumor removal [2476]). A second model trained only on EEA video was also developed. Intraoperative EEA videos from YouTube were used for test data (3 videos, 1239 frames).The YouTube data set contained 2169 total instruments. Mean average precision (mAP) for instrument detection on the YouTube data set was 0.74. The mAP for each individual video was 0.65, 0.74, and 0.89. The second model trained only on EEA video also had an overall mAP of 0.74 (0.62, 0.84, and 0.88 for individual videos). Development costs were $130 for manual video annotation and under $100 for computation.Surgical instruments contained within endoscopic endonasal intraoperative video can be detected using a fully automated ML model. The addition of disparate surgical data sets did not improve model performance, although these data sets may improve generalizability of the model in other use cases.

Disruption of cyclic adenosine monophosphate response element binding protein (CREB) provides a potential new strategy to address acute leukemia, a disease associated with poor prognosis, and for which conventional treatment options often carry a significant risk of morbidity and mortality. We describe the structure-activity relationships (SAR) for a series of XX-650-23 derived from naphthol AS-E phosphate that disrupts binding and activation of CREB by the CREB-binding protein (CBP). Through the development of this series, we identified several salicylamides that are potent inhibitors of acute leukemia cell viability through inhibition of CREB-CBP interaction. Among them, a biphenyl salicylamide, compound 71, was identified as a potent inhibitor of CREB-CBP interaction with improved physicochemical properties relative to previously described derivatives of naphthol AS-E phosphate.

Motivation Quaternary structure determination for transmembrane/soluble proteins requires a reliable computational protocol that leverages observed distance restraints and/or cyclic symmetry (Cn symmetry) found in most homo-oligomeric transmembrane proteins. Results We survey 118 X-ray crystallographically solved structures of homo-oligomeric transmembrane proteins (HoTPs) and find that ∼97% are Cn symmetric. Given the prevalence of Cn symmetric HoTPs and the benefits of incorporating geometry restraints in aiding quaternary structure determination, we introduce two new filters, the distance-restraints (DR) and the Symmetry-Imposed Packing (SIP) filters. SIP relies on a new method that can rebuild the closest ideal Cn symmetric complex from docking poses containing a homo-dimer without prior knowledge of the number (n) of monomers. Using only the geometrical filter, SIP, near-native poses of 7 HoTPs in their monomeric states can be correctly identified in the top-10 for 71% of all cases, or 29% among 31 HoTP structures obtained through homology modeling, while ZDOCK alone returns 14 and 3%, respectively. When the n is given, the optional n-mer filter is applied with SIP and returns the near-native poses for 76% of the test set within the top-10, outperforming M-ZDOCK’s 55% and Sam’s 47%. While applying only SIP to three HoTPs that comes with distance restraints, we found the near-native poses were ranked 1st, 1st and 10th among 54 000 possible decoys. The results are further improved to 1st, 1st and 3rd when both DR and SIP filters are used. By applying only DR, a soluble system with distance restraints is recovered at the 1st-ranked pose. Availability and implementation https://github.com/capslockwizard/drsip. Supplementary information Supplementary data are available at Bioinformatics online.

Determine the long-term outcome and need for additional therapy after pulmonary endarterectomy (PEA) for segmental chronic thromboembolic pulmonary hypertension.Retrospective analysis of a prospective cohort of 401 consecutive Canadian patients undergoing PEA between August 2005 and March 2020 in Toronto. The outcome of segmental disease defined as Jamieson type 3 was compared with more proximal disease defined as Jamieson type 1 and 2. The cohort was divided into 3 intervals to analyze the trend over time: 2005-2010, 2011-2015, and 2016-2020.Type 3 disease accounted for 41% of patients undergoing PEA durig 2016-2020 compared with 7% in 2006-2010. Total pulmonary vascular resistance improved by 505 ± 485 dynes/s/cmPEA achieved excellent early and long-term results in segmental chronic thromboembolic pulmonary hypertension. However, patients with segmental disease are at increased risk of requiring additional therapy after PEA and should be carefully monitored.

Deep neural networks (DNNs) have not been proven to detect blood loss (BL) or predict surgeon performance from video.To train a DNN using video from cadaveric training exercises of surgeons controlling simulated internal carotid hemorrhage to predict clinically relevant outcomes.Video was input as a series of images; deep learning networks were developed, which predicted BL and task success from images alone (automated model) and images plus human-labeled instrument annotations (semiautomated model). These models were compared against 2 reference models, which used average BL across all trials as its prediction (control 1) and a linear regression with time to hemostasis (a metric with known association with BL) as input (control 2). The root-mean-square error (RMSE) and correlation coefficients were used to compare the models; lower RMSE indicates superior performance.One hundred forty-three trials were used (123 for training and 20 for testing). Deep learning models outperformed controls (control 1: RMSE 489 mL, control 2: RMSE 431 mL, R2 = 0.35) at BL prediction. The automated model predicted BL with an RMSE of 358 mL (R2 = 0.4) and correctly classified outcome in 85% of trials. The RMSE and classification performance of the semiautomated model improved to 260 mL and 90%, respectively.BL and task outcome classification are important components of an automated assessment of surgical performance. DNNs can predict BL and outcome of hemorrhage control from video alone; their performance is improved with surgical instrument presence data. The generalizability of DNNs trained on hemorrhage control tasks should be investigated.

Frequent prothrombin time (PT) and international normalized ratio (INR) testing is critical for millions of people on lifelong anticoagulation with warfarin. Currently, testing is performed in hospital laboratories or with expensive point-of-care devices limiting the ability to test frequently and affordably. We report a proof-of-concept PT/INR testing system that uses the vibration motor and camera on smartphones to track micro-mechanical movements of a copper particle. The smartphone system computed the PT/INR with inter-class correlation coefficients of 0.963 and 0.966, compared to a clinical-grade coagulation analyzer for 140 plasma samples and demonstrated similar results for 80 whole blood samples using a single drop of blood (10 μl). When tested with 79 blood samples with coagulopathic conditions, the smartphone system demonstrated a correlation of 0.974 for both PT/INR. Given the ubiquity of smartphones in the global setting, this proof-of-concept technology may provide affordable and effective PT and INR testing in low-resource environments.

Competition is a key biotic factor that often structures natural communities. Many attempts to disentangle how competition shapes natural communities have relied on experiments on simplified systems or through simple mathematical models. But these simplified approaches are limited in their ability to represent the complexity seen in more natural settings. Here, we considered the competitive pairwise dynamics between four saprotrophic fungal species. We tested whether the contextual environment changed these dynamics, repeating competitive experiments in a simple agar media and a more ecologically realistic wood block setting. We found that the competitive outcomes on agar media differed from those within the wood blocks. While superior competitors were identified across all pairwise interactions on agar, within the wood blocks, two of six interactions resulted in deadlock, where neither competitor could breach territory of the other, and one interaction resulted in a reversed competitive outcome. These results suggest that the complexity within natural substrates can alter the strength of interspecific interactions and may contribute to coexistence and the resulting high diversity of fungi often observed within wood.

In this paper, a surgical robot platform with a novel concentric connector joint (CCJ) is presented. The surgical robot is a parallel robot platform comprised of multiple struts, arranged in a geometrically stable array, connected at their end points via the CCJ. The CCJ joints have near-perfect concentricity of rotation around the node point, which enables the tension and compression forces of the struts to be resolved in a structurally-efficient manner. The preliminary feasibility tests, modeling and simulations were introduced.

Plastic packaging is widely used in food industry to protect and maintain food freshness. However, plastic packaging also contributes to solid waste problem and can become the contamination area of microbial activities which in turn affecting the shelf-life of the food product and may causing food-borne illness towards consumer. Thus, the demands on biodegradable polymer as plastic packaging has grown widely especially among the food industry. The employment of silver nanoparticles (AgNPs) can improve physical properties of biopolymer as well as promoting antimicrobial properties on the plastic packaging. The aim of this study is to synthesize of AgNPs by utilising acetylated starch (AS) as reducing agent with different parameters via microwave irradiation method. The effect of different ratio of acetylated starch and microwave time-varying exposure is evaluated. The synthesized silver nanoparticles were characterized via UV-VIS spectroscopy (UV-VIS), X-Ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) analysis. The absorbance peak emerges at 420nm on UV-VIS shows that silver nanoparticles is successfully produced. 15 minutes microwave time exposure and 1:1 ratio is identified as the optimum condition to produce silver nanoparticles. The peak emerges on FTIR spectra shows the involvement of starch in reduction process in synthesizing AgNPs. The XRD results shows the amorphous structure of starch and crystalline peak of silver appear in 2Θ regions 37.4°, 43.4°, 63.1° and 75.7°. In conclusion, the significant outcome from the study is the AgNPs were successfully synthesized via microwave irradiation method and be a function of time varying exposure and acetylated starch ratio.

Background The population detained in the New York City (NYC) jail system bears a high burden of hepatitis C virus (HCV) infection. Challenges to scaling up treatment include short and unpredictable lengths of stay. We report on the clinical outcomes of direct-acting antiviral (DAA) treatment delivered by NYC Health + Hospitals/Correctional Health Services in NYC jails from 2014 to 2017. Methods We performed a retrospective observational cohort study of HCV patients with detectable HCV ribonucleic acid treated with DAA therapy while in NYC jails. Some patients initiated treatment in jail, whereas others initiated treatment in the community and were later incarcerated. Our primary outcome was sustained virologic response at 12 weeks (SVR12). Results There were 269 patients included in our cohort, with 181 (67%) initiating treatment in jail and 88 (33%) continuing treatment started in the community. The SVR12 virologic outcome data were available for 195 (72%) individuals. Of these, 172 (88%) achieved SVR12. Patients who completed treatment in jail were more likely to achieve SVR12 relative to those who were released on treatment (adjusted risk ratio, 2.93; 95% confidence interval, 1.35–6.34). Of those who achieved SVR12, 114 (66%) had a subsequent viral load checked. We detected recurrent viremia in 18 (16%) of these individuals, which corresponded to 10.6 cases per 100 person-years of follow-up. Conclusions Hepatitis C virus treatment with DAA therapy is effective in a jail environment. Future work should address challenges related to discharging patients while they are on treatment, loss to follow-up, and a high incidence of probable reinfection., Treatment of hepatitis C virus (HCV) in the New York City jail system was effective, but challenges remain related to loss to follow-up and reinfection events. Patients discharged from jail while on treatment were less likely to achieve cure.

Objective: There is limited understanding about how people in the severe stages of Alzheimer's disease (AD) experience and demonstrate awareness. We synthesised all available evidence with the aim of understanding how awareness is preserved or impaired in severe AD and what evidence there is for different levels of awareness according to the levels of awareness framework.Method: A systematic search of the following databases: Embase, PsycINFO, MEDLINE and Web of Science was carried out. A narrative synthesis and analysis was conducted of all included studies. All studies were assessed for quality using the AXIS and CASP tools.Results: Our findings suggest that lower level sensory awareness is relatively maintained in severe AD. Findings for higher level awareness are variable and this may be related to the diversity of methods that have been used to explore awareness in these circumstances.Conclusion: Awareness is complex, heterogeneous and varies significantly between individuals. Environmental and contextual factors have a significant impact on whether awareness is observed in people with severe AD. Adaptation of the environment has the potential to facilitate the expression of awareness while education of caregivers may increase understanding of people with severe AD and potentially improve the quality of care that is received.

Our goal is to 3D print wireless sensors, input widgets and objects that can communicate with smartphones and other Wi-Fi devices, without the need for batteries or electronics. To this end, we present a novel toolkit for wireless connectivity that can be integrated with 3D digital models and fabricated using commodity desktop 3D printers and commercially available plastic filament materials. Specifically, we introduce the first computational designs that 1) send data to commercial RF receivers including Wi-Fi, enabling 3D printed wireless sensors and input widgets, and 2) embed data within objects using magnetic fields and decode the data using magnetometers on commodity smartphones. To demonstrate the potential of our techniques, we design the first fully 3D printed wireless sensors including a weight scale, flow sensor and anemometer that can transmit sensor data. Furthermore, we 3D print eyeglass frames, armbands as well as artistic models with embedded magnetic data. Finally, we present various 3D printed application prototypes including buttons, smart sliders and physical knobs that wirelessly control music volume and lights as well as smart bottles that can sense liquid flow and send data to nearby RF devices, without batteries or electronics.

Pulmonary alveolar proteinosis is a rare condition characterized by progressive accumulation of surfactant lipoproteins in the alveolar space, leading to poor gas exchange. We describe our technique of whole lung lavage for management of pulmonary alveolar proteinosis.

Resection of sternal tumors can leave large defects, which exposes major mediastinal structures, and can affect respiratory mechanics. If feasible, resection is potentially a complex reconstructive challenge to restore normal and functional anatomy using conventional techniques. We report the first Australian use of a three-dimensional–printed titanium and PoreStar prosthesis in a 39-year-old woman for reconstruction after major surgical resection of the sternum for metastatic breast cancer. The patient successfully underwent excision of the sternum and costal cartilages as well as implantation of the prosthesis. We conclude that three-dimensional–printed prostheses are technically feasible to deliver excellent cosmetic result.

Elective cardiac surgery accounts for a significant proportion of perioperative resource allocation in Australasia. Preoperative pulmonary function testing (PFT) is routinely undertaken in some centres to identify patients who may require prolonged ventilation and intensive care unit (ICU) stay, although there are currently no data supporting this practice. Routine PFT places a burden on respiratory diagnostic laboratories, is inconvenient to patients and may delay surgery. We aimed to identify whether PFT parameters identify patients requiring prolonged mechanical ventilation after elective cardiac surgery. Adult patients admitted to the Royal Adelaide Hospital ICU following elective cardiac surgery between July 2013 and December 2017 were identified retrospectively from the local ICU database. Preoperative PFT and operative and postoperative outcome data were retrieved from local databases, and multivariable logistic regression was undertaken to identify which PFT variables were associated with prolonged mechanical ventilation. PFT data were available for 835/1139 (73%) elective cardiac surgical cases. The best independent predictors of prolonged mechanical ventilation were post-bronchodilator forced vital capacity (FVC) and single-breath diffusing capacity for carbon monoxide (DLCO). Patients with FVC LCO