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Well-intentioned but ultimately misguided actions over recent decades have contributed to today’s opioid epidemic. Pain was promoted as the “fifth vital sign” as pharmaceutical manufacturers encouraged more liberal prescriptions of new and supposedly safer formulations. When addiction issues became apparent, the pendulum swung toward restricting prescriptions, constraining “street” supply of pharmaceutical opioids. The unintended consequence was creation of new and highly efficient drug distribution pipelines with synthetic opioids to fill market demand. The result has been an epidemic of opioid fatalities, which worsened during the COVID-19 pandemic. This article draws parallels between the current opioid epidemic and a previous tragedy of the marketplace created by Prohibition in the 1920s.

The COVID-19 pandemic created unprecedented demand for hospital and intensive care unit (ICU) services, with excess mortality and length-of-stay (LOS) that may not be attributable to COVID-19 patients alone. We examined risk-adjusted outcomes in adult ICU patients overall, and for subgroups with and without COVID-19. Severity-adjusted mortality, LOS, and ventilator days in COVID-19 patients were higher than expected when adjusted by APACHE for age, chronic illness, and physiology. Non-COVID-19 patients had worse outcomes during high COVID-19 census. These findings have implications for physician executives evaluating and presenting hospital and ICU outcomes during the pandemic.

Influenza is a leading cause of community-acquired pneumonia (CAP), and results of influenza tests can direct therapy. However, among adults hospitalized with CAP, little is known about the frequency and timing of influenza testing, treatment, and their associations with outcomes.In patients with CAP, is testing for influenza associated with antiviral treatment and shorter antibiotic courses, and is early treatment associated with better clinical outcomes?This study included adults admitted with pneumonia in 2010 to 2015 to 179 US hospitals contributing to the Premier database. We assessed influenza testing and compared antimicrobial utilization and the outcomes of test-positive, test-negative, and untested patients. Associations of early antiviral treatment (oseltamivir) with 14-day in-hospital mortality, hospital length of stay, and cost were studied.Among 166,268 patients with CAP, 38,703 (23.3%) were tested for influenza, of whom 11.5% tested positive. Testing increased from 15.4% to 35.6% from 2010 to 2015 and was 28.9% during flu season (October-May) vs 8.2% in June to September. Patients testing positive for influenza received antiviral agents more often and antibacterial agents less often and for shorter courses than patients testing negative (5.3 vs 6.4 days; P .001). Influenza-positive patients receiving oseltamivir on hospital day 1 (n = 2,585) experienced lower 14-day in-hospital mortality (adjusted OR, 0.75; 95% CI, 0.59-0.96), lower costs (adjusted ratio of means, 0.88; 95% CI, 0.81-0.95), and shorter length of stay (adjusted ratio of means, 0.88; 95% CI, 0.84-0.93) vs patients receiving oseltamivir later or not at all (n = 1,742).Even during flu season, most patients with CAP in this study went untested for influenza. A positive influenza test result was associated with antiviral treatment, and early treatment was associated with lower mortality, suggesting that more widespread testing might improve patient outcomes.

Background Community-acquired pneumonia (CAP) is a leading cause of hospital admissions and antimicrobial use. Clinical practice guidelines recommend switching from intravenous (IV) to oral antibiotics once patients are clinically stable. Methods We conducted a retrospective cohort study of adults admitted with CAP and initially treated with IV antibiotics at 642 US hospitals from 2010 through 2015. Switching was defined as discontinuation of IV and initiation of oral antibiotics without interrupting therapy. Patients switched by hospital day 3 were considered early switchers. We compared length of stay (LOS), in-hospital 14-day mortality, late deterioration (intensive care unit [ICU] transfer), and hospital costs between early switchers and others, controlling for hospital characteristics, patient demographics, comorbidities, initial treatments, and predicted mortality. Results Of 378 041 CAP patients, 21 784 (6%) were switched early, most frequently to fluoroquinolones. Patients switched early had fewer days on IV antibiotics, shorter duration of inpatient antibiotic treatment, shorter LOS, and lower hospitalization costs, but no significant excesses in 14-day in-hospital mortality or late ICU admission. Patients at a higher mortality risk were less likely to be switched. However, even in hospitals with relatively high switch rates, Conclusions Although early switching was not associated with worse outcomes and was associated with shorter LOS and fewer days on antibiotics, it occurred infrequently. Even in hospitals with high switch rates

Background: Chronic rhinosinusitis with nasal polyps affects approximately 2–4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps. Methods: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries. Eligible patients were aged 18 years or older with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score of >5), were eligible for repeat nasal surgery (overall symptoms VAS score >7 and endoscopic nasal polyps score of ≥5, with a minimum score of 2 in each nasal cavity) despite standard of care treatment, and had to have at least one nasal surgery in the past 10 years. Patients were randomly assigned (1:1), using permuted block design, to receive either 100 mg mepolizumab subcutaneously or placebo once every 4 weeks, in addition to standard of care (mometasone furoate intranasal spray for at least 8 weeks before screening and during the study, saline nasal irrigations, systemic corticosteroids or antibiotics, or both), as required, for 52 weeks. Site staff, the central study team, and patients were masked to study treatment and absolute blood eosinophil counts. The coprimary endpoints were change from baseline in total endoscopic nasal polyp score at week 52 and in mean nasal obstruction VAS score during weeks 49–52, assessed in the intention-to-treat population (ITT). This study is registered with ClinicalTrials.gov, NCT03085797. Findings: From May 25, 2017, to Dec 12, 2018, 854 patients were screened for eligibility. 414 patients were randomly assigned with 407 included in the ITT population; 206 received mepolizumab and 201 received placebo. Total endoscopic nasal polyp score significantly improved at week 52 from baseline with mepolizumab versus placebo (adjusted difference in medians −0·73, 95% CI −1·11 to −0·34; p

Background Despite interest among North American orthopaedic residents to pursue rotations in resource-limited settings, little is known regarding resident motivations and impact on host surgeons. Methods Surveys were distributed to North American orthopaedic surgeons and trainees who participated in international rotations during residency to assess motivations for participation and to orthopaedic surgeons at partnering low- and middle-income country (LMIC) institutions to assess impact of visiting trainees. Results Responses were received from 136 North American resident rotators and 51 LMIC host surgeons and trainees. North American respondents were motivated by a desire to increase surgical capacity at the LMIC while host surgeons reported a greater impact from learning from residents than on surgical capacity. Negative aspects reported by hosts included selfishness, lack of reciprocity, racial discrimination, competition for surgical experience, and resource burdens. Conclusions The motivations and impact of orthopaedic resident rotations in LMICs need to be aligned. Host perceptions and bidirectional educational exchange should be incorporated into partnership guidelines.

A special class of noise radar that conforms to a frequency modulated (FM) structure has experienced a surge in practical applications in recent years. This article provides a historical context for these random FM waveforms, examines their useful attributes and associated trade-offs, and discusses some of these recent applications.

ObjectivesFracture is a common injury after a traumatic event. The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) to treat acute pain related to fractures is not well established.MethodsClinically relevant questions were determined regarding NSAID use in the setting of trauma-induced fractures with clearly defined patient populations, interventions, comparisons and appropriately selected outcomes (PICO). These questions centered around efficacy (pain control, reduction in opioid use) and safety (non-union, kidney injury). A systematic review including literature search and meta-analysis was performed, and the quality of evidence was graded per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The working group reached consensus on the final evidence-based recommendations.ResultsA total of 19 studies were identified for analysis. Not all outcomes identified as critically important were reported in all studies, and the outcome of pain control was too heterogenous to perform a meta-analysis. Nine studies reported on non-union (three randomized control trials), six of which reported no association with NSAIDs. The overall incidence of non-union in patients receiving NSAIDs compared with patients not receiving NSAIDs was 2.99% and 2.19% (p=0.04), respectively. Of studies reporting on pain control and reduction of opioids, the use of NSAIDs reduced pain and the need for opioids after traumatic fracture. One study reported on the outcome of acute kidney injury and found no association with NSAID use.ConclusionsIn patients with traumatic fractures, NSAIDs appear to reduce post-trauma pain, reduce the need for opioids and have a small effect on non-union. We conditionally recommend the use of NSAIDs in patients suffering from traumatic fractures as the benefit appears to outweigh the small potential risks.

Conversion of provisional external fixation to intramedullary nail (IMN) in femur fractures has been reported to be safe within 14 days of initial surgery. However, there is no current literature guiding this practice in tibial fractures. The purpose of this study was to identify the time period when conversion of external fixation to nail in tibial fractures is safe.After obtaining IRB approval, tibial fractures (OTA 41A, 42, 43A) that received provisional ex-fix and were converted to IMN from 2009 to 2019 were retrospectively reviewed. Skeletally mature patients with minimum 6 months of follow-up were included. The primary outcome was deep infection. External fixation days were categorized as less than 7, 8 to 14, and 15+ days. Risk ratios of infection were estimated using generalized linear regression with a Poisson distribution. A separate regression model evaluated risk factors for infection using both the external fixation and non-external fixation tibial cohorts.Twenty-eight patients (32%) were treated for deep infection. The infection rate for closed fractures was 28% (11 of 39 patients) and for open fractures was 35% (17 of 49 patients) (P = 0.56). Examining both tibial cohorts, external fixation (odds ratio [OR] = 2.39, P = 0.017), open fracture (OR = 3.13, P = 0.002), and compartment syndrome (OR = 2.58, P = 0.01) were all associated with infection in regression modeling. Median external fixation days for patients with deep infection was 8 days (Inter-quartile range, 3 to 18 days) as compared with 4 days (IQR, 2 to 9 days) in patients without infection (P = 0.06). While controlling for open fractures, the 8- to 14-day group had RR = 1.81 (P = 0.2), and the 15+-day group had RR = 2.67 (P = 0.003) as compared with the7-day group.Infection rates of tibial fracture patients treated with external fixation and converted to IMN were high. Surgeons should strongly consider the necessity of external fixation for these fractures. Earlier conversion of external fixation to definitive fixation reduced infection rates.Level IV-case series.

Type II diabetes is considered the most common metabolic disorder in the developed world and currently affects about one in ten globally. A therapeutic target for the management of type II diabetes is the inhibition of α- glucosidase, an essential enzyme located at the brush border of the small intestinal epithelium. The inhibition of α-glucosidase results in reduced digestion of carbohydrates and a decrease in postprandial blood glucose. Although pharmaceutical synthetic inhibitors are available, these are usually associated with significant gastrointestinal side effects. In the present study, the impact of inhibitors derived from edible brown algae is being investigated and compared for their effect on glycaemic control. Carbohydrate- and polyphenolic-enriched extracts derived from Ascophyllum nodosum, Fucus vesiculosus and Undaria pinnatifida were characterised and screened for their inhibitory effects on maltase and sucrase enzymes. Furthermore, enzyme kinetics and the mechanism of inhibition of maltase and sucrase were determined using linear and nonlinear regression methods. All tested extracts showed a dose-dependent inhibitory effect of α-glucosidase with IC50 values ranging from 0⋅26 to 0⋅47 mg/ml for maltase; however, the only extract that was able to inhibit sucrase activity was A. nodosum, with an IC50 value of 0⋅83 mg/ml. The present study demonstrates the mechanisms in which different brown seaweed extracts with varying composition and molecular weight distribution differentially inhibit α-glucosidase activities. The data highlight that all brown seaweed extracts are not equal in the inhibition of carbohydrate digestive enzymes involved in postprandial glycaemia.

BACKGROUND Real-time polymerase chain reaction using nasopharyngeal swabs is currently the most widely used diagnostic test for SARS-CoV-2 detection. However, false negatives and the sensitivity of this mode of testing have posed challenges in the accurate estimation of the prevalence of SARS-CoV-2 infection rates. OBJECTIVE The purpose of this study was to evaluate whether technical and, therefore, correctable errors were being made with regard to nasopharyngeal swab procedures. METHODS We searched a web-based video database (YouTube) for videos demonstrating SARS-CoV-2 nasopharyngeal swab tests, posted from January 1 to May 15, 2020. Videos were rated by 3 blinded rhinologists for accuracy of swab angle and depth. The overall score for swab angle and swab depth for each nasopharyngeal swab demonstration video was determined based on the majority score with agreement between at least 2 of the 3 reviewers. We then comparatively evaluated video data collected from YouTube videos demonstrating the correct nasopharyngeal swab technique with data from videos demonstrating an incorrect nasopharyngeal swab technique. Multiple linear regression analysis with statistical significance set at P=.05 was performed to determine video data variables associated with the correct nasopharyngeal swab technique. RESULTS In all, 126 videos met the study inclusion and exclusion criteria. Of these, 52.3% (66/126) of all videos demonstrated the correct swab angle, and 46% (58/126) of the videos demonstrated an appropriate swab depth. Moreover, 45.2% (57/126) of the videos demonstrated both correct nasopharyngeal swab angle and appropriate depth, whereas 46.8% (59/126) of the videos demonstrated both incorrect nasopharyngeal swab angle and inappropriate depth. Videos with correct nasopharyngeal swab technique were associated with the swab operators identifying themselves as a medical professional or as an Ear, Nose, Throat–related medical professional. We also found an association between correct nasopharyngeal swab techniques and recency of video publication date (relative to May 15, 2020). CONCLUSIONS Our findings show that over half of the videos documenting the nasopharyngeal swab test showed an incorrect technique, which could elevate false-negative test rates. Therefore, greater attention needs to be provided toward educating frontline health care workers who routinely perform nasopharyngeal swab procedures.

BACKGROUND The coronavirus disease (COVID-19) is the latest pandemic of the digital age. With the internet harvesting large amounts of data from the general population in real time, public databases such as Google Trends (GT) and the Baidu Index (BI) can be an expedient tool to assist public health efforts. OBJECTIVE The aim of this study is to apply digital epidemiology to the current COVID-19 pandemic to determine the utility of providing adjunctive epidemiologic information on outbreaks of this disease and evaluate this methodology in the case of future pandemics. METHODS An epidemiologic time series analysis of online search trends relating to the COVID-19 pandemic was performed from January 9, 2020, to April 6, 2020. BI was used to obtain online search data for China, while GT was used for worldwide data, the countries of Italy and Spain, and the US states of New York and Washington. These data were compared to real-world confirmed cases and deaths of COVID-19. Chronologic patterns were assessed in relation to disease patterns, significant events, and media reports. RESULTS Worldwide search terms for shortness of breath, anosmia, dysgeusia and ageusia, headache, chest pain, and sneezing had strong correlations (r>0.60, Pr=0.85, SD 0.10 and r=0.76, SD 0.09, respectively, P CONCLUSIONS This study demonstrates the utility of digital epidemiology in providing helpful surveillance data of disease outbreaks like COVID-19. Although certain online search trends for this disease were influenced by media coverage, many search terms reflected clinical manifestations of the disease and showed strong correlations with real-world cases and deaths.

Prevalence of type 2 diabetes mellitus has significantly increased in the last three decades and currently affects about 1 in 10 globally. A common therapeutic target for type 2 diabetes is α- glucosidase, an essential enzyme located at the brush border of the small intestinal epithelium. The inhibition of α-glucosidase results in a reduced digestion of carbohydrates and a decrease of postprandial blood glucose. Although, synthetic inhibitors are available in the market, these are usually associated with significant gastrointestinal side effects. In this study, natural inhibitors derived from edible brown algae are being investigated as an alternative.Polysaccharide- and polyphenolic-enriched extracts from Ascophyllum nodosum and Fucus vesiculosus were characterized and screened for their inhibitory effects against α-glucosidase obtained from rat intestine using maltose, sucrose, and p-nitrophenyl (pNPG) as substrates. Acarbose was used as a synthetic inhibitor. Furthermore, enzyme kinetics and mechanism of inhibition of α- glucosidase were determined using linear and non-linear regression methods (GraphPad Prism ver. 6, GraphPad Software, La Jolla California USA).All tested extracts showed a dose-dependent inhibitory effect against α-glucosidase. However, the type of inhibition varied between the extracts. Most importantly, the composition analysis showed that the seaweed extracts had different polysaccharide and phenolic contents, suggesting different mode of actions against α-glucosidase. The relation between chemical composition and inhibitory activity of the compounds are discussed.In summary, the current study demonstrates the mechanisms in which different brown seaweed extracts with various composition effectively inhibit α-glucosidase. Therefore, this natural inhibitor can be considered as a potential candidate for the management of type 2 diabetes mellitus.

Author(s): Artenstein, Andrew W.; Rathlev, Niels K.; Neal, Douglas; Townsend, Vernette; Vemula, Michael; Goldlust, Sheila; Schmidt, Joseph; Visintainer, Paul | Abstract: Introduction: Patient progress, the movement of patients through a hospital system from admission todischarge, is a foundational component of operational effectiveness in healthcare institutions. Optimalpatient progress is a key to delivering safe, high-quality and high-value clinical care. The Baystate PatientProgress Initiative (BPPI), a cross-disciplinary, multifaceted quality and process improvement project, waslaunched on March 1, 2014, with the primary goal of optimizing patient progress for adult patients.Methods: The BPPI was implemented at our system’s tertiary care, academic medical center, a highvolume,high-acuity hospital that serves as a regional referral center for western Massachusetts. TheBPPI was structured as a 24-month initiative with an oversight group that ensured collaborative goalalignment and communication of operational teams. It was organized to address critical aspects ofa patient’s progress through his hospital stay and to create additional inpatient capacity. The specificgoal of the BPPI was to decrease length of stay (LOS) on the inpatient adult Hospital Medicine serviceby optimizing an interdisciplinary plan of care and promoting earlier departure of discharged patients.Concurrently, we measured the effects on emergency department (ED) boarding hours per patient andwalkout rates.Results: The BPPI engaged over 300 employed clinicians and non-clinicians in the work. We createdincreased inpatient capacity by implementing daily interdisciplinary bedside rounds to proactively addresspatient progress; during the 24 months, this resulted in a sustained rate of discharge orders writtenbefore noon of more than 50% and a decrease in inpatient LOS of 0.30 days (coefficient: -0.014, 95%CI [-0.023, -0.005] Pl 0.005). Despite the increase in ED patient volumes and severity of illness overthe same time period, ED boarding hours per patient decreased by approximately 2.1 hours (coefficient:-0.09; 95% CI [-0.15, -0.02] P = 0.007). Concurrently, ED walkout rates decreased by nearly 32% to amonthly mean of 0.4 patients (coefficient: 0.4; 95% CI [-0.7, -0.1] P= 0.01).Conclusion: The BPPI realized significant gains in patient progress for adult patients by promotingearlier discharges before noon and decreasing overall inpatient LOS. Concurrently, ED boarding hoursper patient and walkout rates decreased.

OBJECTIVE: To compare the accuracy and reasons for disagreement of two-dimensional (2D) and three-dimensional (3D) echocardiography findings in the assessment of the atrioventricular valve complex in patients with atrioventricular septal defect. METHODS: A total of 20 children (mean age 8 months) with atrioventricular septal defect were enrolled prospectively into this study. The accuracy of and the reasons for disagreement in the assessment of the atrioventricular valve features were analyzed between 2D and 3D echocardiography and surgical findings. RESULTS: We found that in assessing the Rastelli type and the extension of the inferior leaflet into the right ventricle, 3D echocardiography was more accurate compared to 2D echocardiography. In all other features, 2D and 3D echocardiography showed similar accuracy. A significant reason for inaccuracy by both echo modalities was that the technique itself could not visualize the feature, although the image quality was considered to be adequate. In most cases, where it was not possible to visualize the atrioventricular feature by 2D, it was possible by 3D, and vice versa. CONCLUSION: The accuracy of 2D and 3D echocardiography and understanding the potential reasons for disagreements in assessing the atrioventricular valve complex with 2D and 3D can guide the use of those two techniques when combining them in the clinical practice. (Less)

Passive radar can reduce radio frequency (RF) spectrum crowding and facilitate RF system interoperability by eliminating the necessity to transmit. Part 1 of this study discussed a passive multistatic radar experiment using Worldwide Interoperability for Microwave Access (WiMAX) signals of opportunity and the accompanying signal processing techniques that were employed. Part 2 discusses the multistatic velocity backprojection technique for visualising multistatic radar data and applies this technique to simulated data and passive multistatic data from the experiment discussed in Part 1.

Radio frequency (RF) spectrum crowding has resulted in the need for interoperability between radar and communications systems. Passive radar has been investigated as a means to exploit the proliferation of RF systems to perform functions such as detection and tracking of moving targets. Passive multistatic radar may alleviate spectral fratricide by replacing some active monostatic radar systems. Part 1 of this study presents results from a passive multistatic radar experiment that exploits worldwide interoperability for microwave access (WiMAX) communications waveforms to detect moving targets. Signal processing strategies for high-duty cycle, low pulse repetition frequency (PRF) waveforms are discussed and validated on experimental data. Part 2 of this article attempts to address the outstanding research issue of combining data from multistatic radar systems to increase performance.

This chapter begins with a formulation of the RUWO algorithm in Section 18.2 and its application to producing spatial, frequency, and space-frequency transmit nulls for radio frequency interference avoidance, followed by a description of the Naval Research Laboratory's Space Time Adaptive Nulling (STAN) radar test bed, an eight-channel X-band coherent MIMO radar test bed used to experimentally verify the performance of the RUWO algorithm in Section 18.3. Section 18.4 then provides a description of narrowband loop-back and open-air experimental applications of RUWO that were originally presented in [14,15], respectively. Following the narrowband results is an explanation in Section 18.5 of how the RUWO algorithm is incorporated into a method for producing wideband FM waveforms with large space-frequency nulls as discussed in [11]. The chapter concludes with a summary of presented work and a discussion of future work and open problems on the topic of space-time transmit nulling with the goal of RF spectrum interoperability.

Inspired by the fixational movements of the human eye, fast-time spatial modulation was recently demonstrated as a particular physically realizable form of a multiple-input multiple-output (MIMO) radar emission. The attendant coupling of the delay and angle dimensions has been shown to provide a modest improvement in spatial separation, even when using non-adaptive pulse compression and beamforming. Here this continuous emission paradigm is appropriately discretized and a joint delay-angle adaptive filtering strategy is developed that exploits the physical waveform-diverse emission structure to realize significant enhancement in target separability.

This paper describes a unique, multi-channel synthetic aperture radar (MSAR) designed for maritime remote sensing and surveillance research. The X-band system supports two simultaneous transmit channels, excited by arbitrary waveforms, and four simultaneous receive channels, thereby allowing full multiple-input-multiple-output (MIMO) modes. The system antennas are readily reconfigurable to support both along-track and cross-track phase center displacements as well as polarimetric operation. In addition, receive switching is available to provide as many as 32 along-track phase centers. This paper describes the hardware and presents results that illustrate how the along-track phase centers can be used to provide detailed motion measurements across dynamic maritime scenes, using either the Velocity SAR algorithm or a new multi-channel interferometric approach. Imagery recently collected using a combined along-track/cross-track MIMO mode is also presented. The simultaneous velocity and height information provided by this configuration offers new approaches to ocean remote sensing.

Leveraging the recent development of a physical implementation of arbitrary polyphase codes as spectrally well-contained waveforms, the notion of spatial modulation is developed whereby a time-varying beampattern is incorporated into the physical emission of an individual pulse. This subset of the broad category of MIMO radar is inspired by the operation of fixational eye movement within the human eye to enhance visual acuity and also subsumes the notion of the frequency-diverse array for application to pulsed radar. From this spatial modulation framework, some specific emission examples are evaluated in terms of resolution and sidelobe levels for the delay and angle domains. The impact of spatial modulation upon spectral content is also considered and possible joint delay-angle emission design criteria are suggested. Simulation results of selected target arrangements demonstrate the promise of enhanced discrimination and the basis for the development of future cognitive radar capabilities that may mimic salient aspects of the visual cortex.

Acute cellular rejection (ACR) the first year after heart transplantation (HT) and its impact on survival was investigated. All 215 HT patients at our centre 1988-2010, including 219 HTs and 2990 first-year endomyocardial biopsies (EMBs), were studied. 'Routine' EMBs obtained 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40 and 52 weeks after HT, and 'additional clinically indicated' (ACI) EMBs, were graded according to the 1990-ISHLT-WF. The frequency and severity of first-year ACRs was low, with 6.5% of routine EMBs and 14.1% of ACI EMBs showing ACR ≥ grade 2. Proportionally more (P < 0.05) first-year ACRs ≥ grade 2 were found among EMBs in HTs performed during 1988-1999 (9.6%) than 2000-2010 (5.5%), EMBs performed during 16-52 weeks (8.8%) than 1-12 weeks (6.3%) after HT, EMBs in HTs with paediatric (11.3%) than adult (7.1%) donors, and EMBs in sex-mismatched (10.4%) than sex-matched (6.3%) HTs. Five- and ten-year survival was furthermore lower (P < 0.05) among HTs with ≥ 1 compared with 0 first-year ACRs ≥ grade 3A/3B (82% vs. 92% and 69% vs. 82%, respectively). Ten-year survival was 74% compared with 53% in the ISHLT registry. In conclusion, our results indicate that first-year ACRs ≥ grade 3A/3B affect long-term survival. We believe frequent first-year EMBs may allow early ACR detection and continuous immunosuppressive adjustments, preventing low-grade ACRs from progressing to ACRs ≥ grade 3A/3B, thereby improving survival.

Phase-only transmit nulling may help the next generation of radar systems operate in an over-crowded radio frequency spectrum. The reiterative uniform weight optimisation (RUWO) algorithm generates constant modulus radar waveforms with spatial, frequency or space-frequency nulls for multiple-input multiple-output (MIMO) transmit arrays by utilising the maximum signal-to-interference plus noise ratio framework in a reiterative fashion. This study presents loop-back and open air experimental results, obtained using an eight-channel X-band coherent MIMO radar test bed, that demonstrate the use of RUWO to generate constant modulus waveforms that possess spatial and/or frequency nulls. The RUWO algorithm is first used to deterministically generate phase-only weights that produce spatial, frequency or space-frequency nulls at baseband in a loop-back configuration. The algorithm is then utilised to generate weights to produce spatial nulls, both deterministically and adaptively, for the full eight-channel test bed in an open air configuration. The deterministic and adaptive strategies are compared; results demonstrate that RUWO can be used to create spatial nulls and highlight the need for careful calibration of both the transmitter and the receiver.

First popularized in Japan, hydrogen sulfide (H2S) gas suicide is an underreported form of suicide with known risk for secondary disaster. Mortality rate commonly exceeds 90% because of the gas's lethal, noncontained nature. Instances in the United States are increasing, up from 2 cases in 2008 to 18 in 2010. Because H2S poisonings remain rare, there exists a lack of knowledge regarding the residual effects of gas venting after victim extrication. Identifying instances of the efficacious use of personal protection equipment (PPE) is critical in the effort to alleviate risks faced by hospital and rescue personnel. The current case demonstrates the effective use of PPEs after prolonged H2S exposure. In 2011, a 20-year-old man threatened suicide using H2S gas inside a vehicle on a remote rural highway. First responders identified a "rotten egg smell" and subsequently experienced low poisoning symptoms. After prolonged Hazmat-assisted extrication (4 hours) the patient was unconscious and experiencing seizures. He was decontaminated on-scene (20 minutes) and transported to the closest hospital (22 minutes). Ambulance personnel who wore PPE and used the ambulance's reverse ventilation system (RVS)reported no adverse effects. The patient was transferred to the authors' burn facility by helicopter (38 minutes). Life-flight personnel, who did not wear PPE (no ventilatory system available), complained of watery eyes, headache, and dizziness. Hospital personnel, who did not use PPE (or RVS), complained of watery eyes or headache. Exposed personnel demonstrated no deficits or residual effects. In spite of spontaneous movement, the patient began to seize and died. This case is unique given the multiple primary and secondary H2S gas exposures involved. Exposed personnel without RVS and not using PPE demonstrated moderate H2S symptoms. PPE (self-contained breathing apparatuses) and RVS were shown to be effective during an H2S emergency; however, there are currently limited data supporting their appropriate use. Until data demonstrating duration of H2S venting for small enclosed spaces are made available, PPEs should be required.

BACKGROUND: Human herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis. However, insufficiency of standard antiviral treatment against HHV-6 is an emerging problem. OBJECTIVES: To describe the case of child with HHV-6 myocarditis who was treated by unloading with a left ventricular assist device and Artesunate. STUDY DESIGN: Case report supported by histological and viral diagnoses via a combination of histology/immunohistochemistry and polymerase chain reaction techniques performed on cardiac tissues before and after treatment. RESULTS: Following therapeutic intervention, the clinical status and heart function improved. Endomyocardial biopsies revealed decreased levels of HHV-6B DNA in the myocardium and the disappearance of histological findings in support of lymphocytic myocarditis. Left ventricular assist device could be explanted. No adverse effects of Artesunate were noted. CONCLUSIONS: In addition to existing heart failure treatments, Artesunate can be considered as an effective candidate for clinical use in cases of HHV-6B associated myocarditis. (Less)

Gradient descent is an iterative method of determining the minima or maxima of a function. The algorithm can be used to solve a linear system of equations when the computational cost of a matrix inverse is too expensive for an application. Here, gradient descent is applied to Adaptive Pulse Compression (APC), yielding the GraD-APC algorithm. Specifically, a unit-gain constrained version of GraD-APC with optimal step size is derived for use with frequency modulated (FM) waveforms, particularly for cases in which the waveform time-bandwidth product is large enough to prohibit practical use of the original matrix inverse based APC. The range-profile estimation of GraD-APC is compared to that of fully adaptive APC using both simulated and experimentally measured data.

Aims: To evaluate outcome in the first generation of children with end-stage heart disease to whom heart transplantation was available. Methods: Retrospective review of all 135 Swedish children

Introduction: Cardiopulmonary bypass (CPB) surgery remains associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully clarified. Abnormalities in coronary flow and function have beensuggested to play an important role. A few prior studies suggested protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A prior to CPB surgery. Methods: Barrier-bred piglets (10-12 kg, n=20) were subjected to CPB with (n=10) or without (n=10) antegrade administration for 20 minutes of cardioplegic solution. Prior to surgery, half of animals from each group received 10-minute i.v. infusion of 100 mg/kg cyclosporine A. Left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, respectively. Results: Coronary peak flow velocity (cPFV) rose significantly after surgery, especially in cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any timepoint. Conclusions: Cardioplegia during CPB surgery of piglets was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, intracoronary pretreatment with cyclosporine had no observable protective effect on coronary circulation or arrhythmia vulnerability after CPB surgery. (Less)

Human resources (HR) and compensation professionals in Australia were surveyed to determine how they communicate rewards information to employees. The rewards communications survey examined five reward components: organization reward strategy and philosophy, base pay, base-pay increases, short-term variable pay and benefits. This research found that HR and compensation professionals believe that rewards communication is important, even to the degree that it affects organizational performance, employee satisfaction with pay, employee retention and employee motivation. They also believe that most employees have limited understanding of the purpose of reward programs and how they work; in fact, many do not understand aspects of the pay system that directly affect them such as pay ranges, average pay rates and performance targets. Comparisons between Australian and United State reward communication policies and practices are reported.

Adaptive phase-only transmit nulling was previously demonstrated using an eight-channel radar test bed. An error in the calibration software that left one of the transmit elements uncalibrated has since been corrected. New experimental results are presented that demonstrate improved performance relative to previous experiments. In this paper the Reiterative Uniform Weight Optimization (RUWO) algorithm, which utilizes the maximum signal-to-interference plus noise ratio (SINR) framework in a reiterative fashion, is used to generate adaptive phase-only weights from received interference data. Additionally, this work investigates the impact of the bandwidth of the interference signal on the ability to adaptively produce spatial nulls using RUWO.

A new spectral-shaping approach is used to design jointly the amplitude window and phase of a tapered NLFM waveform. This approach can produce physical radar emissions with ultra-low sidelobes that support sufficient spectral roll-off to maintain forthcoming spectral compliance requirements. A small SNR loss is traded for a substantial reduction in range sidelobes. Further, it is demonstrated that this tapered waveform scheme can be readily combined with the linear amplification using nonlinear components (LINC) architecture to realize the small yet necessary amplitude variation while operating the power amplifiers in saturation, which may be used to realize enhanced power efficiency. Experimental measurements demonstrate range sidelobes below −80 dB with less than 0.3 dB in SNR loss.

The sensitivity impact of range straddling in the form of mismatch loss is well known. What is less appreciated, however, is the effect upon dynamic range, particularly for receive filtering that seeks to minimize range sidelobes. For FM-based waveforms, which are readily implementable in a high-power radar system, it is shown that least-squares (LS) mismatched filtering (MMF) realizes a penalty in sidelobe suppression when range straddling occurs. This degradation can be partially compensated through modification of the LS MMF implementation. Alternatively, adaptive pulse compression (APC), appropriately modified for application to FM waveforms, demonstrates robustness to both straddling and eclipsing effects. Simulated and experimentally measured results are provided to demonstrate the efficacy of these filtering approaches.

We aimed to study the incidence, predictors and outcome of chronic kidney disease (CKD) after heart transplantation (HT). All our HT patients 1988-2010 were considered for inclusion. Of these, 134 came for annual follow-ups including evaluation of glomerular filtration rate (GFR) using iohexol clearance measurements, and the CKD-EPI (adults) or Schwartz (children) formulae. Median GFR (Q1-Q3) (ml/min/1.73 m(2) ) declined from 67.0 (50.0-82.0) during transplant assessment (TA) to 56.0 (45.0-69.0) at year 1, 53.0 (41.0-68.0) at year 5 and 44.5 (25.0-57.3) at year 10. The cumulative incidence of CKD ≥ stage 4 was 25% at 5 years and 41% at 10 years after transplantation. Proteinuria the first year post-HT was the only predictor related (P 0.05) to a higher rate of GFR decline (HR 5.15, 95% CI 1.23-21.55). GFR ≥60 as compared to60 before HT, or a first-year GFR decline30% as compared to30%, was moreover associated (P 0.05) with a lower risk of death (HR 0.30, 95% CI 0.12-0.76 and HR 0.35, 95% CI 0.13-0.90, respectively). Notably, the CKD-EPI and Schwartz formulae overestimated GFR by 28 ± 29% and 26 ± 33%, respectively. In conclusion, CKD in HT patients is common and associated with worse outcome. To avoid diagnostic delay, GFR estimating equations' validity in HT patients needs further study.

This paper extends previous work to process and combine data from multiple bistatic pairs in a passive multistatic radar system. The previously presented Multistatic Velocity Backprojection (MVBP) combines and visualizes multistatic radar data. MVBP generates a six-dimensional data cube in position and velocity but does not provide a mechanism for detecting targets within the space. This paper discusses Detection Aided Multistatic Velocity Backprojection (DA-MVBP), a method for seeding MVBP with detections from individual bistatic pairs. DA-MVBP reduces the space through which it is necessary to search for targets in backprojected multistatic radar data and may result in enhanced parameter estimation and detection performance over traditional multilateration of detections. In this work DA-MVBP is applied to experimental passive multistatic radar data.

We consider a class of MIMO radar emissions in which a coherent spatial beam is formed while the direction is modulated during the pulse width. This type of spatial modulation has a direct analog to the rapid, small movements of the human eye during fixation (staring) to enhance contrast and sensitivity to fine detail. To replicate this passive sensing capability of the eye for the active sensing modality of radar we leverage and expand the continuous phase modulation (CPM) framework for code-to-waveform implementation and thereby realize a physical delay-angle coupled emission. Through analysis of a defined angle-delay ambiguity function for specific waveform/spatial modulation examples it is shown that enhanced discrimination is enabled at the cost of some SNR loss, which may be an acceptable tradeoff for some applications.

Phase only transmit nulling may help the next generation of radar systems operate in an over-crowded RF spectrum. Open air experimental results from an eight-channel X-band radar test bed are presented that demonstrate an approach for generating constant modulus waveforms that possess spatial nulls when transmitted from an antenna array. The Re-iterative Uniform Weight Optimization (RUWO) algorithm is utilized to generate phase only weights using both a deterministic and adaptive approach. The two strategies are compared. The results demonstrate that RUWO can be used to create spatial nulls and highlight the need for careful calibration of both the transmitter and receiver.