Publications by authors named "David King"

615 Publications

Hatching date influences winter habitat occupancy: Examining seasonal interactions across the full annual cycle in a migratory songbird.

Ecol Evol 2021 Jul 26;11(14):9241-9253. Epub 2021 Jun 26.

Department of Biology and McCourt School of Public Policy Georgetown University Washington DC USA.

Birds experience a sequence of critical events during their life cycle, and past events can subsequently determine future performance via carry-over effects. Events during the non-breeding season may influence breeding season phenology or productivity. Less is understood about how events during the breeding season affect individuals subsequently in their life cycle. Using stable carbon isotopes, we examined carry-over effects throughout the annual cycle of prairie warblers (), a declining Nearctic-Neotropical migratory passerine bird. In drier winters, juvenile males that hatched earlier at our study site in Massachusetts, USA, occupied wetter, better-quality winter habitat in the Caribbean, as indicated by depleted carbon isotope signatures. For juveniles that were sampled again as adults, repeatability in isotope signatures indicated similar winter habitat occupancy across years. Thus, hatching date of juvenile males appears to influence lifetime winter habitat occupancy. For adult males, reproductive success did not carry over to influence winter habitat occupancy. We did not find temporally consecutive "domino" effects across the annual cycle (breeding to wintering to breeding) or interseasonal, intergenerational effects. Our finding that a male's hatching date can have a lasting effect on winter habitat occupancy represents an important contribution to our understanding of seasonal interactions in migratory birds.
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http://dx.doi.org/10.1002/ece3.7500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293775PMC
July 2021

Stevens-Johnson syndrome associated with Hodgkin's lymphoma.

Pediatr Dermatol 2021 Jul 16. Epub 2021 Jul 16.

Department of Paediatric Oncology, Sheffield Children's Hospital NHS Foundation Trust, Western Bank, Sheffield, UK.

Hodgkin's lymphoma accounts for approximately 40% of all lymphomas presenting in childhood and can be associated with a variety of dermatologic manifestations. Here, we describe a case of Hodgkin's lymphoma presenting with Stevens-Johnson syndrome. Clinicians should be aware of this association, especially if no alterative trigger for Stevens-Johnson syndrome can be identified.
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http://dx.doi.org/10.1111/pde.14716DOI Listing
July 2021

Elastic response of wire frame glasses. II. Three-dimensional systems.

J Chem Phys 2021 Jun;154(24):244905

Cavendish Laboratory, University of Cambridge, J J Thomson Ave., Cambridge CB3 0HE, United Kingdom.

We study the elastic response of rigid wire frame particles in concentrated glassy suspensions to a step strain by applying the simple geometric methods developed in Paper I. The wire frame particles are comprised of thin rigid rods of length L, and their number density, ρ, is such that ρL ≫ 1. We specifically compare rigid rods to L-shapes made of two equal length rods joined at right angles. The behavior of wire frames is found to be strikingly different from that of rods. The linear elasticity scales like ρL for L-shaped particles, whereas it scales proportional to ρ for rods and the non-linear response shows a transition from shear hardening to shear softening at a critical density ρ∼K/kTL, where K is the bending modulus of the particles. For realistic particles made of double stranded DNA, this transition occurs at densities of about ρL ∼ 10. The reason for these differences is that wire frames can be forced to bend by the entanglements with their surroundings, whereas rods always remain straight. This is found to be very important even for small strains, with most particles being bent above a critical strain γ∼ρL .
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http://dx.doi.org/10.1063/5.0046525DOI Listing
June 2021

Elastic response of wire frame glasses. I. Two dimensional model.

J Chem Phys 2021 Jun;154(24):244904

Cavendish Laboratory, University of Cambridge, J J Thomson Ave., Cambridge CB3 0HE, United Kingdom.

We study the elastic response of concentrated suspensions of rigid wire frame particles to a step strain. These particles are constructed from infinitely thin, rigid rods of length L. We specifically compare straight rod-like particles to bent and branched wire frames. In dense suspensions, the wire frames are frozen in a disordered state by the topological entanglements between their arms. We present a simple, geometric method to find the scaling of the elastic stress with concentration in these glassy systems. We apply this method to a simple 2D model system where a test particle is placed on a plane and constrained by a random distribution of points with number density ν. Two striking differences between wire frame and rod suspensions are found: (1) The linear elasticity per particle for wire frames is very large, scaling like νL, whereas for rods, it is much smaller and independent of concentration. (2) Rods always shear thin but wire frames shear harden for concentrations less than ∼K/kTL, where K is the bending modulus of the particles. The deformation of wire frames is found to be important even for small strains, with the proportion of deformed particles at a particular strain, γ, being given by (νL)γ. Our results agree well with simple numerical calculations for the 2D system.
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http://dx.doi.org/10.1063/5.0046524DOI Listing
June 2021

Severe Acute Respiratory Syndrome Coronavirus 2 Testing Trends Among Persons Aged <18 Years in an Outpatient Pediatric Practice - Metropolitan Atlanta, Georgia, May-December 2020.

J Adolesc Health 2021 07;69(1):144-148

CDC COVID-19 Response Team, Centers for Disease Control and Prevention, Atlanta, Georgia.

Purpose: The purpose of this study was to analyze trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and test positivity among persons aged <18 years in a three-site outpatient pediatric practice in Atlanta, Georgia, serving approximately 35,000 pediatric patients.

Methods: Using electronic medical records, weekly trends in SARS-CoV-2 tests performed and the 14-day moving average of test positivity were examined, overall and by age group, during May 24-December 5, 2020.

Results: Among 4,995 patients who received at least 1 SARS-CoV-2 test, 6,813 total tests were completed. Overall test positivity was 5.4% and was higher among older pediatric patients (<5 years: 3.3%; 5-11 years: 4.1%; 12-17 years: 8.6%). The number of tests and test positivity increased after holidays and school breaks.

Conclusions: Families might benefit from communication focused on reducing SARS-CoV-2 transmission during holidays. In addition, given higher test positivity in children aged 12-17 years, tailoring public health messaging to older adolescents could help limit SARS-CoV-2 transmission risk in this population.
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http://dx.doi.org/10.1016/j.jadohealth.2021.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219291PMC
July 2021

Abdominal Wall Thickness Predicts Surgical Site Infection in Emergency Colon Operations.

J Surg Res 2021 Jun 12;267:37-47. Epub 2021 Jun 12.

Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Body mass index (BMI) does not reliably predict Surgical site infections (SSI). We hypothesize that abdominal wall thickness (AWT) would serve as a better predictor of SSI for patients undergoing emergency colon operations.

Methods: We retrospectively evaluated our Emergency Surgery Database (2007-2018). Emergency colon operations for any indication were included. AWT was measured by pre-operative CT scans at 5 locations. Only superficial and deep SSIs were considered as SSI in the analysis. Univariate then multivariable analyses were used to determine predictors of SSI.

Results: 236 patients met inclusion criteria. The incidence of post-operative SSI was 25.8% and the median BMI was 25.8kg/m [22.5-30.1]. The median AWT between patients with and without SSI was significantly different (2.1cm [1.4, 2.8] and 1.8cm [1.2, 2.5], respectively). A higher BMI trended toward increased rates of SSI, but this was not statistically significant. In overweight (BMI 25-29.9kg/m) and obese (BMI ≥30kg/m) patients, SSI versus no SSI rates were (50.0% versus 41.9% and 47.4% versus 36.4%, P = 0.365 and 0.230) respectively. The incidence of SSI in patients with an average AWT < 1.8cm was 20% and 30% for patients with average AWT ≥1.8cm. On multivariable analysis, AWT ≥1.8cm at 2cm inferior to umbilicus was an independent predictor of SSI (OR 2.98, 95%CI 1.34-6.63, P = 0.007).

Conclusions: AWT is a better predictor of SSI than BMI. Preoperative imaging of AWT may direct intraoperative decisions regarding wound management. Future clinical outcomes research in emergency surgery should include abdominal wall thickness as an important patient variable.
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http://dx.doi.org/10.1016/j.jss.2021.04.038DOI Listing
June 2021

Generating indicator species for bird monitoring within the humid forests of northeast Central America.

Environ Monit Assess 2021 Jun 12;193(7):413. Epub 2021 Jun 12.

University of Massachusetts Amherst, Amherst, MA, 01003, USA.

The use of indicator species can simplify bird monitoring by reducing the level of specialized skills needed, which increases the potential pool of participants and reduces training costs and complexity. To facilitate monitoring in the humid forests of northeast Central America, we conducted point count surveys for birds across gradients of disturbance in the Cockscomb Basin Wildlife Sanctuary, Belize, and analyzed the association of bird species with remotely sensed metrics of forest condition and anthropogenic disturbance using indicator species analysis. Twenty species exhibited significant associations with one or more of these metrics. We propose six species as indicators for anthropogenic disturbance based on our criteria of being associated with anthropogenically disturbed sites, or anthropogenically disturbed and riparian sites with no explicit mention in the literature of an obligate association with riparian habitats, or association of remotely sensed metrics that appeared to reflect disturbance: yellow-olive flycatcher, red-legged honeycreeper, dusky antbird, blue ground dove, buff-throated saltator, and brown jay. We propose the keel-billed motmot as an indicator of undisturbed forest based on its association with forested sites in our analyses. Green shrike vireo, collard trogon, rufous-tailed jacamar, and rufous piha were associated with a specific elevational range but not associated with disturbance, so upward shifts in elevation that might indicate response to climate change would not be confounded with habitat disturbance or degradation. This exercise yielded a much-reduced list of monitoring targets, which will greatly reduce the cost and complexity of forest bird monitoring in the region, as well as reducing barriers to participation.
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http://dx.doi.org/10.1007/s10661-021-09172-1DOI Listing
June 2021

Characterising Foot-and-Mouth Disease Virus in Clinical Samples Using Nanopore Sequencing.

Front Vet Sci 2021 17;8:656256. Epub 2021 May 17.

Vesicular Disease Reference Laboratory, The Pirbright Institute, Woking, United Kingdom.

The sequencing of viral genomes provides important data for the prevention and control of foot-and-mouth disease (FMD) outbreaks. Sequence data can be used for strain identification, outbreak tracing, and aiding the selection of the most appropriate vaccine for the circulating strains. At present, sequencing of FMD virus (FMDV) relies upon the time-consuming transport of samples to well-resourced laboratories. The Oxford Nanopore Technologies' MinION portable sequencer has the potential to allow sequencing in remote, decentralised laboratories closer to the outbreak location. In this study, we investigated the utility of the MinION to generate sequence data of sufficient quantity and quality for the characterisation of FMDV serotypes O, A, Asia 1. Prior to sequencing, a universal two-step RT-PCR was used to amplify parts of the 5'UTR, as well as the leader, capsid and parts of the 2A encoding regions of FMDV RNA extracted from three sample matrices: cell culture supernatant, tongue epithelial suspension and oral swabs. The resulting consensus sequences were compared with reference sequences generated on the Illumina MiSeq platform. Consensus sequences with an accuracy of 100% were achieved within 10 and 30 min from the start of the sequencing run when using RNA extracted from cell culture supernatants and tongue epithelial suspensions, respectively. In contrast, sequencing from swabs required up to 2.5 h. Together these results demonstrated that the MinION sequencer can be used to accurately and rapidly characterise serotypes A, O, and Asia 1 of FMDV using amplicons amplified from a variety of different sample matrices.
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http://dx.doi.org/10.3389/fvets.2021.656256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165188PMC
May 2021

LCD-Composer: an intuitive, composition-centric method enabling the identification and detailed functional mapping of low-complexity domains.

NAR Genom Bioinform 2021 Jun 26;3(2):lqab048. Epub 2021 May 26.

Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.

Low complexity domains (LCDs) in proteins are regions predominantly composed of a small subset of the possible amino acids. LCDs are involved in a variety of normal and pathological processes across all domains of life. Existing methods define LCDs using information-theoretical complexity thresholds, sequence alignment with repetitive regions, or statistical overrepresentation of amino acids relative to whole-proteome frequencies. While these methods have proven valuable, they are all indirectly quantifying amino acid composition, which is the fundamental and biologically-relevant feature related to protein sequence complexity. Here, we present a new computational tool, LCD-Composer, that directly identifies LCDs based on amino acid composition and linear amino acid dispersion. Using LCD-Composer's default parameters, we identified simple LCDs across all organisms available through UniProt and provide the resulting data in an accessible form as a resource. Furthermore, we describe large-scale differences between organisms from different domains of life and explore organisms with extreme LCD content for different LCD classes. Finally, we illustrate the versatility and specificity achievable with LCD-Composer by identifying diverse classes of LCDs using both simple and multifaceted composition criteria. We demonstrate that the ability to dissect LCDs based on these multifaceted criteria enhances the functional mapping and classification of LCDs.
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http://dx.doi.org/10.1093/nargab/lqab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153834PMC
June 2021

Minimally Invasive Stabilization with or without Ablation for Metastatic Periacetabular Tumors.

J Bone Joint Surg Am 2021 Jul;103(13):1184-1192

The Medical College of Wisconsin, Milwaukee, Wisconsin.

Background: Metastatic bone disease in the periacetabular region represents a potentially devastating problem for patients. Surgical treatment can offer pain relief and restore function. We describe a series of patients treated with minimally invasive osteoplasty and screw fixation with or without ablation.

Methods: Thirty-eight patients with 16 different metastatic tumor subtypes were managed with osteoplasty and screw fixation with or without ablation at a single institution. A retrospective review was performed to determine functional outcomes with use of the 1993 Musculoskeletal Tumor Society (MSTS) score as well as changes in narcotic usage.

Results: MSTS scores improved for all patients following surgery. Narcotic usage decreased in >80% of patients. Approximately half of the operations were outpatient procedures. Complications were minimal, there were no delays in chemotherapy or radiation due to surgical wound concerns, and there were no surgery-related deaths. The mean duration of follow-up was 9 months, with a 39% survival rate at the time of writing. Six of the 12 patients who survived for >1 year required additional procedures at a mean of 12 months (range, 4 to 23 months).

Conclusions: Treatment of periacetabular metastatic disease with minimally invasive stabilization with or without ablation provides pain relief and functional improvement with lower complication rates than previously reported open reconstruction techniques. The minimally invasive approach allows for rapid initiation of chemotherapy and radiation. Patients with particularly aggressive cancers that are poorly responsive to systemic therapies and radiation may have progression of disease and may require additional procedures. Conversion to total hip arthroplasty was uncomplicated, and the cement and screw constructs were retained, providing a stable base for the arthroplasty reconstruction.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.20.00546DOI Listing
July 2021

Development of a field artificial intelligence triage tool: Confidence in the prediction of shock, transfusion, and definitive surgical therapy in patients with truncal gunshot wounds.

J Trauma Acute Care Surg 2021 Jun;90(6):1054-1060

From the Division of Trauma, Emergency Surgery and Surgical Critical Care (TESSC) (C.J.N., A.K.M., O.A., J.A.F., J.J.P., A.E.M., P.J.F., H.M.A.K., D.R.K., G.C.V., N.S.), Massachusetts General Hospital (MGH), Boston, Massachusetts; Department of Trauma Surgery (C.J.N.), Leiden University Medical Center, Leiden, The Netherlands; Lincoln Laboratory (T.T., J.R., M.C.), Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts; and Center for Outcomes and Patient Safety in Surgery (H.M.A.K), Massachusetts General Hospital (MGH), Boston, Massachusetts.

Background: In-field triage tools for trauma patients are limited by availability of information, linear risk classification, and a lack of confidence reporting. We therefore set out to develop and test a machine learning algorithm that can overcome these limitations by accurately and confidently making predictions to support in-field triage in the first hours after traumatic injury.

Methods: Using an American College of Surgeons Trauma Quality Improvement Program-derived database of truncal and junctional gunshot wound (GSW) patients (aged 16-60 years), we trained an information-aware Dirichlet deep neural network (field artificial intelligence triage). Using supervised training, field artificial intelligence triage was trained to predict shock and the need for major hemorrhage control procedures or early massive transfusion (MT) using GSW anatomical locations, vital signs, and patient information available in the field. In parallel, a confidence model was developed to predict the true-class probability (scale of 0-1), indicating the likelihood that the prediction made was correct, based on the values and interconnectivity of input variables.

Results: A total of 29,816 patients met all the inclusion criteria. Shock, major surgery, and early MT were identified in 13.0%, 22.4%, and 6.3% of the included patients, respectively. Field artificial intelligence triage achieved mean areas under the receiver operating characteristic curve of 0.89, 0.86, and 0.82 for prediction of shock, early MT, and major surgery, respectively, for 80/20 train-test splits over 1,000 epochs. Mean predicted true-class probability for errors/correct predictions was 0.25/0.87 for shock, 0.30/0.81 for MT, and 0.24/0.69 for major surgery.

Conclusion: Field artificial intelligence triage accurately identifies potential shock in truncal GSW patients and predicts their need for MT and major surgery, with a high degree of certainty. The presented model is an important proof of concept. Future iterations will use an expansion of databases to refine and validate the model, further adding to its potential to improve triage in the field, both in civilian and military settings.

Level Of Evidence: Prognostic, Level III.
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http://dx.doi.org/10.1097/TA.0000000000003155DOI Listing
June 2021

Modified Frailty Index-5 Score and Post-Operative Infectious Complications in Patients Undergoing Surgery for Intestinal-Cutaneous Fistula: A Nationwide Retrospective Cohort Analysis.

Surg Infect (Larchmt) 2021 Apr 29. Epub 2021 Apr 29.

Division of Trauma, Emergency Surgery, and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Post-operative infectious complications after repair of intestinal-cutaneous fistulas (ICF) represent a substantial burden and these outcomes vary widely in the literature. We aimed to evaluate the use of the modified frailty index-5 (mFI-5) to account for physiologic reserve to predict infectious complications in patients with ICF undergoing operative repair. We used the American College of Surgeon National Surgical Quality Improvement Program (ACS-NSQIP) 2006-2017 dataset to include patients who underwent ICF repair. The main outcome measure was 30-day infectious complications (surgical site infection [SSI], sepsis, pneumonia, and urinary tract infection [UTI]). The risk of 30-day post-operative infectious complications was assessed based on mFI-5 score. We performed multivariable logistic regression analyses to evaluate the association between infectious complications and mFI-5. We identified 4,197 patients who underwent an ICF repair. The median age (interquartile range [IQR]) was 57 (46, 67) years, and the majority of patients were female (2,260; 53.9%); white (3,348; 79.8%); and 1,586 (38.3%) were obese. After adjustment for relevant confounders such as baseline patient characteristics, and operative details, mFI-5 was independently associated with infectious complications (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.25-3.21), particularly SSI (OR, 2.16; 95% CI, 1.28-3.63) and pneumonia (OR, 5.31; 95% CI, 2.29-12.35), but not UTI or sepsis. We showed that the mFI-5 is a strong predictor of infectious complications after ICF repair. It can be utilized to account for physiologic reserve, therefore reducing the variability of outcomes reported for ICF repair.
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http://dx.doi.org/10.1089/sur.2020.441DOI Listing
April 2021

Multi-segment foot kinematics during gait following ankle arthroplasty.

J Orthop Res 2021 Apr 29. Epub 2021 Apr 29.

Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Ankle arthritis is a debilitating disease marked by pain and limited function. Total ankle arthroplasty improves pain while preserving motion and offers an alternative to the traditional treatment of ankle fusion. Gait analysis and functional outcomes tools can provide an objective balanced analysis of ankle replacement for the treatment of ankle arthritis. Twenty-nine patients with end-stage ankle arthritis were evaluated before and after ankle arthroplasty. Multi-segment foot and ankle kinematics were assessed annually following surgery (average 3.5 years, range 1-6 years) using the Milwaukee Foot Model and a Vicon video motion analysis system. Functional outcomes (American Orthopedic Foot and Ankle Society [AOFAS] ankle/hindfoot scale, short form 36 [SF-36] questionnaire) and temporal-spatial parameters were also assessed. Kinematic results were compared to findings from a previously collected group of healthy ambulators. AOFAS and SF-36 mean scores improved postoperatively. Walking speed and stride length increased after surgery. There were significant improvements in tibial sagittal range of motion in terminal stance and hindfoot sagittal range of motion in preswing. Decreased external rotation of the tibia and increased external rotation of the hindfoot were noted throughout the gait cycle. Pain and function improved after ankle replacement as supported by better outcomes scores, increased temporal-spatial parameters, and significant improvement in tibial sagittal range of motion during terminal stance and hindfoot sagittal range of motion during preswing. While multi-segment foot kinematics were improved, they were not restored to control values. Statement of clinical significance: Total ankle arthroplasty does not fully normalize mutli-segment gait kinematics despite improved patient-reported outcomes and gait mechanics.
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http://dx.doi.org/10.1002/jor.25062DOI Listing
April 2021

Multisystem outcomes and predictors of mortality in critically ill patients with COVID-19: Demographics and disease acuity matter more than comorbidities or treatment modalities.

J Trauma Acute Care Surg 2021 05;90(5):880-890

From the Division of Trauma, Emergency Surgery and Surgical Critical Care (O.A., A.M., L.N., K.L., K.A.B., M.E.M., C.K., A.G., M.A.C., L.R.M., H.M., B.B.-K., J.P., J.F., N.S., A.M., C.P., P.F., D.K., J.L., G.C.V., H.M.A.K.), and Division of Pulmonary Critical Care (M.R.F.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Background: We sought to describe characteristics, multisystem outcomes, and predictors of mortality of the critically ill COVID-19 patients in the largest hospital in Massachusetts.

Methods: This is a prospective cohort study. All patients admitted to the intensive care unit (ICU) with reverse-transcriptase-polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 14, 2020, and April 28, 2020, were included; hospital and multisystem outcomes were evaluated. Data were collected from electronic records. Acute respiratory distress syndrome (ARDS) was defined as PaO2/FiO2 ratio of ≤300 during admission and bilateral radiographic pulmonary opacities. Multivariable logistic regression analyses adjusting for available confounders were performed to identify predictors of mortality.

Results: A total of 235 patients were included. The median (interquartile range [IQR]) Sequential Organ Failure Assessment score was 5 (3-8), and the median (IQR) PaO2/FiO2 was 208 (146-300) with 86.4% of patients meeting criteria for ARDS. The median (IQR) follow-up was 92 (86-99) days, and the median ICU length of stay was 16 (8-25) days; 62.1% of patients were proned, 49.8% required neuromuscular blockade, and 3.4% required extracorporeal membrane oxygenation. The most common complications were shock (88.9%), acute kidney injury (AKI) (69.8%), secondary bacterial pneumonia (70.6%), and pressure ulcers (51.1%). As of July 8, 2020, 175 patients (74.5%) were discharged alive (61.7% to skilled nursing or rehabilitation facility), 58 (24.7%) died in the hospital, and only 2 patients were still hospitalized, but out of the ICU. Age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12), higher median Sequential Organ Failure Assessment score at ICU admission (OR, 1.24; 95% CI, 1.06-1.43), elevated creatine kinase of ≥1,000 U/L at hospital admission (OR, 6.64; 95% CI, 1.51-29.17), and severe ARDS (OR, 5.24; 95% CI, 1.18-23.29) independently predicted hospital mortality.Comorbidities, steroids, and hydroxychloroquine treatment did not predict mortality.

Conclusion: We present here the outcomes of critically ill patients with COVID-19. Age, acuity of disease, and severe ARDS predicted mortality rather than comorbidities.

Level Of Evidence: Prognostic, level III.
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http://dx.doi.org/10.1097/TA.0000000000003085DOI Listing
May 2021

The relationship between vitamin D status, intake and exercise performance in UK University-level athletes and healthy inactive controls.

PLoS One 2021 2;16(4):e0249671. Epub 2021 Apr 2.

Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.

The potential ergogenic effects of vitamin D (vitD) in high performing athletes has received considerable attention in the literature and media. However, little is known about non-supplemented university athletes and students residing at a higher latitude. This study aimed to investigate the effects of vitD (biochemical status and dietary intake) on exercise performance in UK university athletes and sedentary students. A total of 34 athletes and 16 sedentary controls were studied during the spring and summer months. Serum vitD status and sunlight exposure were assessed using LC-MS/MS and dosimetry, respectively. Muscular strength of the upper and lower body was assessed using handgrip and knee extensor dynamometry (KE). Countermovement jump (CMJ) and aerobic fitness were measured using an Optojump and VO2max test, respectively. Statistical analysis was performed using paired/ independent t-tests, ANCOVA and Pearson/ Spearman correlations, depending on normality. VitD status increased significantly over the seasons, with athletes measuring higher status both in spring (51.7±20.5 vs. 37.2±18.9 nmol/L, p = 0.03) and summer (66.7±15.8 vs 55.6±18.8 nmol/L, p = 0.04) when compared to controls, respectively. Notably, 22% of the subjects recruited were vitD deficient during the spring term only (<25nmol/L, n 9). Subjects with 'insufficient' vitD status (<50nmol/L) elicited significantly lower CMJ when contrasted to the vitD 'sufficient' (>50nmol/l) group (p = 0.055) and a lower VO2 max (p = 0.05) in the spring and summer term (p = 0.05 and p = 0.01, respectively). However, an ANCOVA test showed no significant difference detected for either CMJ or VO2max following adjustments for co-variates. In conclusion, we provide novel information on the vitD status, dietary intake, physical fitness and sunlight exposure of UK young adults across two separate seasons, for which there is limited data at present.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249671PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018647PMC
April 2021

Dipnictogen f-Element Chemistry: A Diphosphorus Uranium Complex.

J Am Chem Soc 2021 Apr 1;143(14):5343-5348. Epub 2021 Apr 1.

Department of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, U.K.

The first isolation and structural characterization of an f-element dinitrogen complex was reported in 1988, but an f-element complex with the first heavier group 15 homologue diphosphorus has to date remained unknown. Here, we report the synthesis of a side-on bound diphosphorus complex of uranium(IV) using a 7λ-(dimethylamino)phosphadibenzonorbornadiene-mediated P atom transfer approach. Experimental and computational characterization reveals that the diphosphorus ligand is activated to its dianionic (P) form and that in-plane U-P π-bonding dominates the bonding of the U(μ-η:η-P)U unit, which is supplemented by a weak U-P interaction of δ symmetry. A preliminary reactivity study demonstrates conversion of this diphosphorus complex to unprecedented uranium -P complexes, suggesting generation of transient, reactive phosphido species.
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http://dx.doi.org/10.1021/jacs.1c02482DOI Listing
April 2021

Peri-operative blood transfusion and risk of infectious complications following intestinal-cutaneous fistula surgical repair: A retrospective nationwide analysis.

Am J Surg 2021 Mar 11. Epub 2021 Mar 11.

Division of Trauma, Emergency Surgery and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Background: Peri-operative blood transfusion (BT) may lead to transfusion-induced immunomodulation. We aimed to investigate the association between peri-operative BT and infectious complications in patients undergoing intestinal-cutaneous fistulas (ICF) repair.

Methods: We queried the ACS-NSQIP 2006-2017 database to include patients who underwent ICF repair. The main outcome was 30-day infectious complications. Univariate and multivariable logistic regression analyses were performed to assess the predictors of post-operative infections.

Results: Of 4,197 patients included, 846 (20.2%) received peri-operative BT. Transfused patients were generally older, sicker and had higher ASA (III-V). After adjusting for relevant covariates, patients who received intra and/or post-operative (and not pre-operative) BT had higher odds of infectious complications compared (OR = 1.22, 95% CI 1.01-1.48). Specifically, they had higher odds of organ-space surgical site infection (OR = 1.61, 95% CI 1.21-2.13), but not other infectious complications.

Conclusions: Intra and/or post-operative (and not pre-operative) BT is an independent predictor of infectious complications in ICF repair.
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http://dx.doi.org/10.1016/j.amjsurg.2021.03.013DOI Listing
March 2021

SCREENING HOSPITAL STAFF WITH CORE SYMPTOMS MAY MISS CASES OF COVID-19.

J Paediatr Child Health 2021 04 18;57(4):595-596. Epub 2021 Mar 18.

Department of Paediatric Oncology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom.

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http://dx.doi.org/10.1111/jpc.15447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250691PMC
April 2021

Effects of post-exercise sodium bicarbonate ingestion on acid-base balance recovery and time-to-exhaustion running performance: a randomised crossover trial in recreational athletes.

Appl Physiol Nutr Metab 2021 Mar 17. Epub 2021 Mar 17.

University of Surrey, 3660, Surrey Human Performance Institute, Guildford, United Kingdom of Great Britain and Northern Ireland;

This study investigated the effect of post-exercise sodium bicarbonate (NaHCO3) ingestion on acid-base balance recovery and time-to-exhaustion (TTE) running performance. Eleven male runners (stature, 1.80 ± 0.05 m; body mass, 74.4 ± 6.5 kg; maximal oxygen consumption, 51.7 ± 5.4 ml.kg-1.min-1) participated in this randomised, single-blind, counterbalanced and crossover design study. Maximal running velocity (v-VO2max) was identified from a graded exercise test. During experimental trials, participants repeated 100% v-VO2max TTE protocols (TTE1, TTE2) separated by 40 min following the ingestion of either 0.3 g.kg-1 BM NaHCO3 (SB) or 0.03 g.kg-1 BM sodium chloride (PLA) at the start of TTE1 recovery. Acid-base balance (blood pH and bicarbonate, HCO3-) data were studied at baseline, post-TTE1, after 35 min recovery and post-TTE2. Blood pH and [HCO3-] were unchanged at 35 min recovery (p > 0.05), but [HCO3-] was elevated post-TTE2 for SB vs. PLA (+2.6 mmol.l-1; p = 0.005; g = 0.99). No significant differences were observed for TTE2 performance (p > 0.05), although a moderate effect size was present for SB vs. PLA (+14.3 s; g = 0.56). Post-exercise NaHCO3 ingestion is not an effective strategy for accelerating the restoration of acid-base balance or improving subsequent TTE performance when limited recovery is available. Novelty bullets: •Post-exercise sodium bicarbonate ingestion did not accelerate the restoration of blood pH or bicarbonate after 35 minutes •Performance enhancing effects of sodium bicarbonate ingestion may display a high degree of inter-individual variation •Small-to-moderate changes in performance were likely due to greater up-regulation of glycolytic activation during exercise.
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http://dx.doi.org/10.1139/apnm-2020-1120DOI Listing
March 2021

The Role of Transaminases in Predicting Choledocholithiasis. A Novel Predictive Composite Score Development in a Cohort of 1089 Patients Undergoing Laparoscopic Cholecystectomy.

Am Surg 2021 Mar 12:3134821998664. Epub 2021 Mar 12.

Department of Surgery, Harvard Medical School, 548305Massachusetts General Hospital, Boston, MA, USA.

Background: Optimal use of interventional procedures and diagnostic tests for patients with suspected choledocholithiasis depends on accurate pretest risk estimation. We sought to define sensitivity/specificity of transaminases in identifying choledocholithiasis and to incorporate them into a biochemical marker composite score that could accurately predict choledocholithiasis.

Methods: All adult patients who underwent laparoscopic cholecystectomy by our Emergency Surgery Service between 2010 and 2018 were reviewed. Admission total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) was captured. Choledocholithiasis was confirmed via intraoperative cholangiogram, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography. Area under receiver operating characteristic curve (AUC) or C-statistic for AST, ALT, ALP, and TB as a measure of detecting choledocholithiasis was calculated. For score development, our database was randomly dichotomized to derivation and validation cohort and a score was derived. The score was validated by calculating its C-statistic.

Results: 1089 patients were included; 210 (20.3%) had confirmed choledocholithiasis. The AUC was .78 for TB, .77 for ALP and AST, and .76 for ALT. 545 and 544 patients were included in the derivation and the validation cohort, respectively. The elements of the derived score were TB, AST, and ALP. The score ranged from 0 to 4. The AUC was .82 in the derivation and .77 in the validation cohort. The probability of choledocholithiasis increased from 8% to 89% at scores 0 to 4, respectively.

Conclusions: Aspartate aminotransferase predicted choledocholithiasis adequately and should be featured in choledocholithiasis screening algorithms. We developed a biochemical composite score, shown to be accurate in preoperative choledocholithiasis risk assessment in an emergency surgery setting.
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http://dx.doi.org/10.1177/0003134821998664DOI Listing
March 2021

Genomic characterization of 99 viruses from the bunyavirus families Nairoviridae, Peribunyaviridae, and Phenuiviridae, including 35 previously unsequenced viruses.

PLoS Pathog 2021 03 1;17(3):e1009315. Epub 2021 Mar 1.

Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.

Bunyaviruses (Negarnaviricota: Bunyavirales) are a large and diverse group of viruses that include important human, veterinary, and plant pathogens. The rapid characterization of known and new emerging pathogens depends on the availability of comprehensive reference sequence databases that can be used to match unknowns, infer evolutionary relationships and pathogenic potential, and make response decisions in an evidence-based manner. In this study, we determined the coding-complete genome sequences of 99 bunyaviruses in the Centers for Disease Control and Prevention's Arbovirus Reference Collection, focusing on orthonairoviruses (family Nairoviridae), orthobunyaviruses (Peribunyaviridae), and phleboviruses (Phenuiviridae) that either completely or partially lacked genome sequences. These viruses had been collected over 66 years from 27 countries from vertebrates and arthropods representing 37 genera. Many of the viruses had been characterized serologically and through experimental infection of animals but were isolated in the pre-sequencing era. We took advantage of our unusually large sample size to systematically evaluate genomic characteristics of these viruses, including reassortment, and co-infection. We corroborated our findings using several independent molecular and virologic approaches, including Sanger sequencing of 197 genome segments, and plaque isolation of viruses from putative co-infected virus stocks. This study contributes to the described genetic diversity of bunyaviruses and will enhance the capacity to characterize emerging human pathogenic bunyaviruses.
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http://dx.doi.org/10.1371/journal.ppat.1009315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951987PMC
March 2021

Persistent confusion in nutrition and obesity research about the validity of classic nonparametric tests in the presence of heteroscedasticity: evidence of the problem and valid alternatives.

Am J Clin Nutr 2021 03;113(3):517-524

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

The use of classic nonparametric tests (cNPTs), such as the Kruskal-Wallis and Mann-Whitney U tests, in the presence of unequal variance for between-group comparisons of means and medians may lead to marked increases in the rate of falsely rejecting null hypotheses and decreases in statistical power. Yet, this practice remains prevalent in the scientific literature, including nutrition and obesity literature. Some nutrition and obesity studies use a cNPT in the presence of unequal variance (i.e., heteroscedasticity), sometimes because of the mistaken rationale that the test corrects for heteroscedasticity. Herein, we discuss misconceptions of using cNPTs in the presence of heteroscedasticity. We then discuss assumptions, purposes, and limitations of 3 common tests used to test for mean differences between multiple groups, including 2 parametric tests: Fisher's ANOVA and Welch's ANOVA; and 1 cNPT: the Kruskal-Wallis test. To document the impact of heteroscedasticity on the validity of these tests under conditions similar to those used in nutrition and obesity research, we conducted simple simulations and assessed type I error rates (i.e., false positives, defined as incorrectly rejecting the null hypothesis). We demonstrate that type I error rates for Fisher's ANOVA, which does not account for heteroscedasticity, and Kruskal-Wallis, which tests for differences in distributions rather than means, deviated from the expected significance level. Greater deviation from the expected type I error rate was observed as the heterogeneity increased, especially in the presence of an imbalanced sample size. We provide brief tutorial guidance for authors, editors, and reviewers to identify appropriate statistical tests when test assumptions are violated, with a particular focus on cNPTs.
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http://dx.doi.org/10.1093/ajcn/nqaa357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948897PMC
March 2021

A Paradigm Shift in Critical Care Infrastructure in Complex Settings: Evaluating an Ultraportable Operating Room to Improve Field Surgical Safety.

Mil Med 2021 01;186(Suppl 1):295-299

Department of Research and Development, Surgi Box Inc, Cambridge, MA 02139, USA.

Introduction: Scarcity of operating rooms and personal protective equipment in far-forward field settings make surgical infections a potential concern for combat mortality and morbidity. Surgical and transport personnel also face infectious risks from bodily fluid exposures. Our study aimed to describe the serial, proof-of-concept testing of the SurgiBox technology: an inflatable sterile environment that addresses the aforementioned problems, fits on gurneys and backpacks, and drapes over incisions.

Materials And Methods: The SurgiBox environmental control unit and inflatable enclosure were optimized over five generations based on iterative feedback from stakeholders experienced in surgery in austere settings. The airflow system was developed by analytic modeling, verified through in silico modeling in SOLIDWORKS, and confirmed with prototype smoke-trail checking. Particulate counts evaluated the enclosure's ability to control and mitigate users' exposures to potentially infectious contaminants from the surgical field in various settings. SurgiBox enclosures were setup over a mannequin's torso, in a configuration and position for either thoracic or abdominal surgery. A particle counter was serially positioned in sternotomy and laparotomy positions, as well as bilateral flank positions. This setup was repeated with open ports exposing the enclosure to the external environment. To simulate stress scenarios, sampling was repeated with enclosure measurements during an increase in external particulate concentration.

Results: The airflow technology effectively kept contaminants away from the incision and maintained a pressure differential to reduce particle entry. Benchtop testing demonstrated that even when ports were opened or the external environment had high contaminant burden, the enclosed surgical field consistently registered 0 particle count in all positions. Time from kit opening to incision averaged 54.5 seconds, with the rate-limiting step being connecting the environmental control unit to the enclosure. The portable kit weighted 5.9 lbs.

Conclusions: Analytic, in silico, and mechanical airflow modeling and benchtop testing have helped to quantify the SurgiBox system's reliability in creating and maintaining an operating room-quality surgical field within the enclosure as well as protecting the surgical team outside the enclosure. More recent and ongoing work has focused on specifying optimal use settings in the casualty chain of care, expanding support for circumferential procedures, automating airflow control, and accelerating system setup. SurgiBox's ultimate goal is to take timely, safe surgery to patients in even the most austere of settings.
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http://dx.doi.org/10.1093/milmed/usaa311DOI Listing
January 2021

Minimally Invasive Stabilization of Periacetabular Metastasis.

Instr Course Lect 2021 ;70:475-492

Metastatic bone disease to the pelvis can lead to lower quality of life and function secondary to pain. Historically, treatment was palliative with radiation therapy and chemotherapy used to reduce pain. The Harrington procedure and subsequent modifications improved pain and function. In the subset of patients with complications, this would delay potential life-prolonging interventions such as chemotherapy and radiation therapy. Percutaneous palliative pain procedures including ablation and cementoplasty have been developed by interventional radiology for pelvic lesions and have been shown to be safe and efficacious. Additionally, percutaneous methods of pelvic fracture fixation have been developed. Modern image guidance technologies have allowed an expanded multidisciplinary approach to pelvic metastatic disease in a minimally invasive fashion with combinations of ablation, internal fixation, and cementation to improve patient quality of life and outcomes with decreased morbidity and rapid return to radiation and systemic therapies.
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January 2021

Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study.

Toxins (Basel) 2020 Dec 20;12(12). Epub 2020 Dec 20.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn-Tolosa-Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, = 19; placebo, = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 ( 0.003) and Week 8 ( 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 ( < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 ( 0.004) and Week 8 ( < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.
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http://dx.doi.org/10.3390/toxins12120807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766785PMC
December 2020

Preoperative frailty predicts postoperative outcomes in intestinal-cutaneous fistula repair.

Surgery 2021 05 4;169(5):1199-1205. Epub 2021 Jan 4.

Division of Trauma, Emergency Surgery and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Electronic address:

Background: The outcomes of operative repair of intestinal-cutaneous fistulas vary widely throughout the literature. We aimed to investigate whether the modified frailty index-5 is a reliable tool to account for physiologic reserve and whether it serves as a predictor of Clavien-Dindo grade IV complications in those with intestinal-cutaneous fistulas undergoing operative repair.

Methods: We queried the American College of Surgeons National Surgical Quality Improvement Program 2006 to 2017 database to include patients who underwent intestinal-cutaneous fistulas repair. The outcome of interest was 30-day Clavien-Dindo grade IV complications. The incidence of 30-day post-operative Clavien-Dindo grade IV complications were evaluated based on calculated modified frailty index-5 score. Multivariable logistic regression analyses were performed to assess the association of Clavien-Dindo grade IV complications and modified frailty index-5.

Results: A total of 3,995 patients were identified who underwent an intestinal-cutaneous fistulas repair. The median age (interquartile range) was 57 years (46, 67), and most patients were female (2,143 [53.7%]), White (3,206 [80.3%]), and 1,512 (38.2%) were obese. After adjusting for relevant covariates such as demographics, comorbidities, and operative details, modified frailty index-5 was independently associated with Clavien-Dindo grade IV complications (odds ratio = 2.81, 95% confidence interval 1.64-4.82; P < .001).

Conclusion: Modified frailty index-5 is an independent predictor of Clavien-Dindo grade IV complications following intestinal-cutaneous fistulas repair. It can be used to account for physiologic reserve, thus reducing the variability of outcomes reported for intestinal-cutaneous fistulas repair.
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http://dx.doi.org/10.1016/j.surg.2020.11.018DOI Listing
May 2021

Investigating the role of matrix habitat use in determining avian area-sensitivity.

Ecol Evol 2020 Dec 13;10(23):12792-12800. Epub 2020 Nov 13.

U.S. Forest Service Northern Research Station University of Massachusetts Amherst MA USA.

The absence of some species from small habitat patches has long posed a challenge for conservationists, yet the underlying mechanisms that cause this "area-sensitivity" remain poorly understood. Capacity of a species to extend their activities into the surrounding matrix habitat represents one potential determinant of area-sensitivity. Species may be able to occupy smaller patches if they can utilize matrix habitat beyond patch boundaries, whereas area-sensitive species may be restricted to larger patches due to their inability to utilize the surrounding matrix. We investigated the potential role of matrix utilization in determining area-sensitivity by mapping the movements of two shrubland-obligate passerines with contrasting patch area requirements in shrub-dominated forest openings ranging in area by nearly an order of magnitude. Our findings were consistent with our predictions; the less area-sensitive chestnut-sided warbler () exhibited greater use of matrix habitat than the highly area-sensitive prairie warbler (). Furthermore, chestnut-sided warblers that occupied smaller openings used mature forest more than conspecifics in larger patches, yet forest use by prairie warblers was unrelated to opening size. Chestnut-sided warblers foraged as frequently in mature forest as within shrubland, whereas prairie warblers foraged significantly more in openings compared to forest. The findings of this study suggest that the ability or inclination of a species to utilize surrounding matrix habitat explains at least some of the observed variation in area-sensitivity in songbirds and potentially other taxa.
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http://dx.doi.org/10.1002/ece3.6810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713974PMC
December 2020

Pelvis weight-bearing ability after minimally invasive stabilizations for periacetabular lesion.

J Orthop Res 2020 Dec 10. Epub 2020 Dec 10.

Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Periacetabular metastatic lesions cause debilitating weight-bearing pain and pose a risk of pelvic pathologic fracture. Minimally invasive percutaneous stabilization is an alternative palliative therapy over extensive open reconstructive surgeries. This study aimed to investigate the biomechanical behaviors of three distinct techniques of percutaneous periacetabular stabilization. A total of 20 composite hemipelves custom-made to contain Harrington type III periacetabular lesion based on a patient's computed tomograpy scans were assigned to treatment groups of cementoplasty alone using polymethyl methacrylate (Cement), screw fixation alone using ischial and posterior-to-anterior screws (Screws), cement-augmented screws (Screws&Cement), and a control group (Untreated). All hemipelves were loaded in a mechanical test configuration mimicking a single-legged stance, and failure load, failure deformation, and construct stiffness were determined. In the experiments, Screws&Cement demonstrated the highest yield strength (4711 ± 362 N) and was 12% higher than Cement (4005 ± 304 N, p = 0.019), 125% higher than Screws (2097 ± 359 N, p < 0.0001), and 184% higher than Untreated (1658 ± 254 N, p < 0.0001). No significant difference in yield strength was found between Screws and Untreated. Screws&Cement also demonstrated the highest stiffness (1013 ± 92 N/mm), followed by Cement (893 ± 49 N/mm), and both groups were significantly stiffer than Screws (543 ± 114 N/mm, p < 0.0001) and Untreated (580 ± 91 N/mm, p < 0.0001 for Screws&Cement, and p = 0.0003 for Cement). This study demonstrated that a cement-augmented periacetabular reconstruction is an effective option for percutaneous treatment of Harrington III periacetabular metastatic lesion. The addition of pelvic screws over cementoplasty significantly improved the pelvis load-bearing strength. When large periacetabular lesions are present, augmented screw fixation appears to be the superior choice of treatment.
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http://dx.doi.org/10.1002/jor.24945DOI Listing
December 2020

Baseline results of a living systematic review for COVID-19 clinical trial registrations.

Wellcome Open Res 2020 2;5:116. Epub 2020 Jun 2.

Infectious Diseases Data Observatory (IDDO), Oxford, UK.

Since the coronavirus disease 2019 (COVID-19) outbreak was first reported in December 2019, many independent trials have been planned that aim to answer similar questions. Tools allowing researchers to review studies already underway can facilitate collaboration, cooperation and harmonisation. The Infectious Diseases Data Observatory (IDDO) has undertaken a living systematic review (LSR) to provide an open, accessible and frequently updated resource summarising characteristics of COVID-19 study registrations. Review of all eligible trial records identified by systematic searches as of 3 April 2020 and initial synthesis of clinical study characteristics were conducted. In partnership with Exaptive, an open access, cloud-based knowledge graph has been created using the results.  There were 728 study registrations which met eligibility criteria and were still active. Median (25 , 75 percentile) sample size was 130 (60, 400) for all studies and 134 (70, 300) for RCTs. Eight lower middle and low income countries were represented among the planned recruitment sites. Overall 109 pharmacological interventions or advanced therapy medicinal products covering 23 drug categories were studied. Majority (57%, 62/109) of them were planned only in one study arm, either alone or in combination with other interventions. There were 49 distinct combinations studied with 90% (44/49) of them administered in only one or two study arms. The data and interactive platform are available at https://iddo.cognitive.city/.  Baseline review highlighted that the majority of investigations in the first three months of the outbreak were small studies with unique treatment arms, likely to be unpowered to provide solid evidence.  The continued work of this LSR will allow a more dependable overview of interventions tested, predict the likely strength of evidence generated, allow fast and informative filtering of relevant trials for specific user groups and provide the rapid guidance needed by investigators and funders to avoid duplication of efforts.
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http://dx.doi.org/10.12688/wellcomeopenres.15933.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610178PMC
June 2020

One-way-street revisited: Streamlined admission of critically-ill trauma patients.

Am J Emerg Med 2020 10 26;38(10):2028-2033. Epub 2020 Jun 26.

Harvard Affiliated Emergency Medicine Residency at Massachusetts General Hospital and Brigham and Women's Hospital, United States of America; Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital, Boston, MA, United States of America; Department of Emergency Medicine, Harvard Medical School, Boston, MA, United States of America. Electronic address:

Introduction: Emergency department (ED) crowding is associated with increased mortality and delays in care. We developed a rapid admission pathway targeting critically-ill trauma patients in the ED. This study investigates the sustainability of the pathway, as well as its effectiveness in times of increased ED crowding.

Materials & Methods: This was a retrospective cohort study assessing the admission of critically-ill trauma patients with and without the use of a rapid admission pathway from 2013 to 2018. We accessed demographic and clinical data from trauma registry data and ED capacity logs. Statistical analyses included univariate and multivariate testing.

Results: A total of 1700 patients were included. Of this cohort, 434 patients were admitted using the rapid admission pathway, whereas 1266 were admitted using the traditional pathway. In bivariate analysis, mean ED LOS was 1.54 h (95% Confidence Interval [CI]: 1.41, 1.66) with the rapid pathway, compared with 5.88 h (95% CI: 5.64, 6.12) with the traditional pathway (p < 0.01). We found no statistically significant relationship between rapid admission pathway use and survival to hospital discharge. During times of increased crowding, rapid pathway use continued to be associated with reduction in ED LOS (p < 0.01). The reduction in ED LOS was sustained when comparing initial results (2013-2014) to recent data (2015-2018).

Conclusion: This study found that a streamlined process to admit critically-ill trauma patients is sustainable and associated with reduction in ED LOS. As ED crowding remains pervasive, these findings support restructured care processes to limit prolonged ED boarding times for critically-ill patients.
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http://dx.doi.org/10.1016/j.ajem.2020.06.043DOI Listing
October 2020
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