title: [Risk assessment of global COVID-19 imported cases into China].

text: Objective: To assess the risk of COVID-19 foreign imports cases to China. Methods: We collected epidemic data (cumulative daily confirmed cases in each country, cumulative confirmed imported cases), demographic data (population density, population) and information on potential source groups of tourists (the daily estimated number of overseas Chinese, overseas Chinese students, overseas workers, foreign students coming to China and flight passengers) and the global health security index (GHS) to assess and predict risk of imported cases for recent (February 1st to April 25th) and future (after April 26th). Results: Strong positive correlation was found among variables including the number of imported cases, cumulative confirmed cases, attack rate, number of overseas Chinese, number of overseas Chinese students, number of foreign students coming to China, number of flight passengers and GHS. In the recent risk analysis, imported cases of Russian were the highest, followed by United Kingdom, United States, France and Spain. In the future risk prediction, 44 countries including United States and Singapore are evaluated as potential high-risk countries in the future through the attack rate index of each country and the estimated average number of daily passengers. Conclusion: The risk assessment of COVID-19 imported cases can be used to identify high-risk areas in recent and future, and might be helpful to strengthen the prevention and control of the epidemic and ultimately overcome the epidemic.


How to Prevent and Manage Hospital-Based Infections During Coronavirus Outbreaks: Five Lessons from Taiwan.


title: Incidence of microemboli and correlation with platelet inhibition in aneurysmal flow diversion.

text: Flow-diverting stents have been associated with embolic and hemorrhagic complications, but the rate of procedure-related microemboli is unknown. Using transcranial Doppler sonography, we measured the rate of microemboli in 23 patients treated with flow-diverting stents. Patients received preprocedural dual antiplatelet medications and intraprocedural heparinization. Point-of-care platelet reactivity testing was performed before the procedure, and nonresponders (>213 P2Y12/ADP receptor reactivity units) received additional thienopyridine. Transcranial Doppler sonography was performed within 12-24 hours. Microemboli were detected in 3 patients (13%), 2 of whom were initially nonresponders. There was no association between the presence of microemboli and procedural or neurologic complications, aneurysm size, number of stents, or procedure time. Eight procedures (34.8%) required additional thienopyridine for inadequate platelet inhibition, and 3 required further treatment for persistent nonresponse to point-of-care platelet reactivity testing. There were 6 technical and 2 postoperative complications; none were associated with inadequate platelet inhibition or microemboli. The combination of routine point-of-care platelet reactivity testing and postprocedural microembolic monitoring may help identify patients at risk for thromboembolic complications after flow-diverting stents.


title: Personal protection and delivery of rhinologic and endoscopic skull base procedures during the COVID-19 outbreak.

text: On March 11th 2020, the World Health Organization (WHO) declared COVID-19 pandemic, with subsequent profound impact on the entire health care system. During the COVID-19 outbreak, activities in the rhinology outpatient clinic and operation rooms are limited to emergency care only. Health care practitioners are faced with the need to perform rhinological and skull base emergency procedures in patients with a positive or unknown COVID-19 status. This article aims to provide recommendations and relevant information for rhinologists, based on the limited amount of (anecdotal) data, to guarantee high-quality patient care and adequate levels of infection prevention in the rhinology clinic.


title: Clinical Recommendations for Epistaxis Management During the COVID-19 Pandemic.

text: Epistaxis is a common complaint in the general population, and its treatment is a common procedure in emergency departments. In the COVID-19 era, procedures involving airway management are a particular risk for health care workers due to the high virulence of the virus, the transmission through aerosol, and the risk of contagion from asymptomatic patients. In this article, we propose a simple memorandum of clinical recommendations to minimize the risk of operator infection deriving from epistaxis management. The correct use of personal protective equipment and strict compliance with the behavioral guidelines are essential to reduce the potential risk of infection. In particular, the use of filtering masks is strongly recommended since all patients, including those referring for epistaxis, should be treated as being COVID-19 positive in the emergency department. The safety of health care workers is essential not only to safeguard continuous patient care but also to limit virus transmission.


title: Emerging and neglected tropical diseases: translational application of proteomics.

text: The challenges of identifying and controlling emerging diseases impact individual health, as well as political, social and economic situations. In this review we discuss the role of proteomics for investigation of pathogen discovery, outbreak investigation, bio-defense, disease control, host-pathogen dynamics and vaccine development of emerging and neglected tropical diseases (NTDs). In the future the discipline of proteomics may help define multiple aspects of emerging and NTDs with respect to personalized medicine and public health.


title: Laparoscopic vessel sealing technologies.

text: Laparoscopic vessel sealing devices have revolutionized modern laparoscopy. These devices fall into 2 major categories: advanced bipolar and ultrasonic instruments. The range of tissue effects available with these technologies is more limited than with conventional monopolar electrosurgery; however, both advanced bipolar and ultrasonic devices efficiently seal vessels (≤7-mm and ≤5-mm diameter, respectively), and most also have built-in tissue transection capabilities. These technologies have been the subject of a range of comparative studies on their relative advantages and disadvantages, and, to date, neither advanced bipolar or ultrasonic devices has been proven to be superior.


title: Brain Injury and Neurologic Outcome in Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

text: OBJECTIVES Extracorporeal cardiopulmonary resuscitation has shown survival benefit in select patients with refractory cardiac arrest but there is insufficient data on the frequency of different types of brain injury. We aimed to systematically review the prevalence, predictors of and survival from neurologic complications in patients who have undergone extracorporeal cardiopulmonary resuscitation. DATA SOURCES MEDLINE (PubMed) and six other databases (EMBASE, Cochrane Library, CINAHL Plus, Web of Science, and Scopus) from inception to August 2019. STUDY SELECTION Randomized controlled trials and observational studies in patients greater than 18 years old. DATA EXTRACTION Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for randomized controlled trials, the Newcastle-Ottawa Scale for cohort and case-control studies, and the Murad tool for case series. Random-effects meta-analyses were used to pool data. DATA SYNTHESIS The 78 studies included in our analysis encompassed 50,049 patients, of which 6,261 (12.5%) received extracorporeal cardiopulmonary resuscitation. Among extracorporeal cardiopulmonary resuscitation patients, the median age was 56 years (interquartile range, 52-59 yr), 3,933 were male (63%), 3,019 had out-of-hospital cardiac arrest (48%), and 2,289 had initial shockable heart rhythm (37%). The most common etiology of cardiac arrest was acute coronary syndrome (n = 1,657, 50% of reported). The median extracorporeal cardiopulmonary resuscitation duration was 3.2 days (interquartile range, 2.1-4.9 d). Overall, 27% (95% CI, 0.17-0.39%) had at least one neurologic complication, 23% (95% CI, 0.14-0.32%) hypoxic-ischemic brain injury, 6% (95% CI, 0.02-0.11%) ischemic stroke, 6% (95% CI, 0.01-0.16%) seizures, and 4% (95% CI, 0.01-0.1%) intracerebral hemorrhage. Seventeen percent (95% CI, 0.12-0.23%) developed brain death. The overall survival rate after extracorporeal cardiopulmonary resuscitation was 29% (95% CI, 0.26-0.33%) and good neurologic outcome was achieved in 24% (95% CI, 0.21-0.28%). CONCLUSIONS One in four patients developed acute brain injury after extracorporeal cardiopulmonary resuscitation and the most common type was hypoxic-ischemic brain injury. One in four extracorporeal cardiopulmonary resuscitation patients achieved good neurologic outcome. Further research on assessing predictors of extracorporeal cardiopulmonary resuscitation-associated brain injury is necessary.


title: Japanese Encephalitis Virus NS5 Inhibits Type I Interferon (IFN) Production by Blocking the Nuclear Translocation of IFN Regulatory Factor 3 and NF-κB.

text: The type I interferon (IFN) response is part of the first-line defense against viral infection. To initiate replication, viruses have developed powerful evasion strategies to counteract host IFN responses. In the present study, we found that the Japanese encephalitis virus (JEV) NS5 protein could inhibit double-stranded RNA (dsRNA)-induced IFN-β expression in a dose-dependent manner. Our data further demonstrated that JEV NS5 suppressed the activation of the IFN transcriptional factors IFN regulatory factor 3 (IRF3) and NF-κB. However, there was no defect in the phosphorylation of IRF3 and degradation of IκB, an upstream inhibitor of NF-κB, upon NS5 expression, indicating a direct inhibition of the nuclear localization of IRF3 and NF-κB by NS5. Mechanistically, NS5 was shown to interact with the nuclear transport proteins KPNA2, KPNA3, and KPNA4, which competitively blocked the interaction of KPNA3 and KPNA4 with their cargo molecules, IRF3 and p65, a subunit of NF-κB, and thus inhibited the nuclear translocation of IRF3 and NF-κB. Furthermore, overexpression of KPNA3 and KPNA4 restored the activity of IRF3 and NF-κB and increased the production of IFN-β in NS5-expressing or JEV-infected cells. Additionally, an upregulated replication level of JEV was shown upon KPNA3 or KPNA4 overexpression. These results suggest that JEV NS5 inhibits the induction of type I IFN by targeting KPNA3 and KPNA4.IMPORTANCE JEV is the major cause of viral encephalitis in South and Southeast Asia, with high mortality. However, the molecular mechanisms contributing to the severe pathogenesis are poorly understood. The ability of JEV to counteract the host innate immune response is potentially one of the mechanisms responsible for JEV virulence. Here we demonstrate the ability of JEV NS5 to interfere with the dsRNA-induced nuclear translocation of IRF3 and NF-κB by competitively inhibiting the interaction of IRF3 and NF-κB with nuclear transport proteins. Via this mechanism, JEV NS5 suppresses the induction of type I IFN and the antiviral response in host cells. These findings reveal a novel strategy for JEV to escape the host innate immune response and provide new insights into the pathogenesis of JEV.


title: Farnesoid X receptor knockout protects brain against ischemic injury through reducing neuronal apoptosis in mice.

text: BACKGROUND Farnesoid X receptor (FXR) is a nuclear receptor that plays a critical role in controlling cell apoptosis in diverse diseases. Previous studies have shown that knocking out FXR improved cardiac function by reducing cardiomyocyte apoptosis in myocardial ischemic mice. However, the role of FXR after cerebral ischemia remains unknown. In this study, we explored the effects and mechanisms of FXR knockout (KO) on the functional recovery of mice post cerebral ischemia-reperfusion. METHODS Adult male C57BL/6 wild type and FXR KO mice were subjected to 90-min transient middle cerebral artery occlusion (tMCAO). The mice were divided into five groups: sham, wild-type tMCAO, FXR KO tMCAO, wild-type tMCAO treated with calcium agonist Bayk8644, and FXR KO tMCAO treated with Bayk8644. FXR expression was examined using immunohistochemistry and Western blot. Brain infarct and brain atrophy volume were examined at 3 and 14 days after stroke respectively. Neurobehavioral tests were conducted up to 14 days after stroke. The protein levels of apoptotic factors (Bcl-2, Bax, and Cleaved caspase-3) and mRNA levels of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IL-17, and IL-18) were examined using Western blot and RT-PCR. TUNEL staining and calcium imaging were obtained using confocal and two-photon microscopy. RESULTS The expression of FXR was upregulated after ischemic stroke, which is located in the nucleus of the neurons. FXR KO was found to reduce infarct volume and promote neurobehavioral recovery following tMCAO compared to the vehicle. The expression of apoptotic and pro-inflammatory factors decreased in FXR KO mice compared to the control. The number of NeuN+/TUNEL+ cells declined in the peri-infarct area of FXR KO mice compared to the vehicle. We further demonstrated that inhibition of FXR reduced calcium overload and addition of ionomycin could reverse this neuroprotective effect in vitro. What is more, in vivo results showed that enhancement of intracellular calcium concentrations could aggravate ischemic injury and reverse the neuroprotective effect of FXR KO in mice. CONCLUSIONS FXR KO can promote neurobehavioral recovery and attenuate ischemic brain injury, inflammatory release, and neuronal apoptosis via reducing calcium influx, suggesting its role as a therapeutic target for stroke treatments.


Technology Gap Deepened by Coronavirus Pandemic.


title: National Clinical Guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy.

text: PURPOSE To summarise recommendations about 20 non-surgical interventions for recent onset (<12 weeks) non-specific low back pain (LBP) and lumbar radiculopathy (LR) based on two guidelines from the Danish Health Authority. METHODS Two multidisciplinary working groups formulated recommendations based on the GRADE approach. RESULTS Sixteen recommendations were based on evidence, and four on consensus. Management of LBP and LR should include information about prognosis, warning signs, and advise to remain active. If treatment is needed, the guidelines suggest using patient education, different types of supervised exercise, and manual therapy. The guidelines recommend against acupuncture, routine use of imaging, targeted treatment, extraforaminal glucocorticoid injection, paracetamol, NSAIDs, and opioids. CONCLUSION Recommendations are based on low to moderate quality evidence or on consensus, but are well aligned with recommendations from international guidelines. The guideline working groups recommend that research efforts in relation to all aspects of management of LBP and LR be intensified.


title: Endoscopic Ovariectomy of Exotic Mammals Using a Three-Port Approach.

text: Laparoscopic ovariectomy has been advocated as the preferred sterilization method for dogs for some time. The same arguments and benefits can be extended for many zoologic mammals, including carnivores, suids, primates, lagomorphs, and large rodents. This article summarizes the benefits, equipment options, surgical technique, recovery, and complications associated with this sterilization procedure.


title: Combined Endoscopic and Laparoscopic Surgery.

text: Benign colon polyps are best treated endoscopically. Colon polyps that are not amenable for endoscopic removals either because they are too large or situated in anatomically difficult locations can pose a clinical dilemma. Traditionally the most common recommendation for these patients has been to offer a colon resection. Although the laparoscopic approach has improved short-term outcomes, morbidities associated with bowel resection are still significant. We may be over treating majority of these patients because of the remote possibility that these polyps may be harboring a cancer. A combined approach using both laparoscopy and colonoscopy (combined endoscopic and laparoscopic surgery) has been described as an alternative to bowel resection in select patients with polyps that cannot be removed endoscopically. Polyp removal using this combined approach may be an effective alternative in select patients.


title: The combination of baseline magnetic resonance perfusion-weighted imaging-derived tissue volume with severely prolonged arterial-tissue delay and diffusion-weighted imaging lesion volume is predictive of MCA-M1 recanalization in patients treated with endovascular thrombectomy.

text: INTRODUCTION Indices of collateral flow deficit derived from MR perfusion imaging that are predictive of MCA-M1 recanalization after intravenous thrombolysis have been recently reported. Our objective was to test the performance of such MRI-derived collateral flow indices for prediction of recanalization after endovascular thrombectomy. METHODS Fifty-seven patients with MCA-M1 occlusion evaluated with multimodal MRI prior to thrombectomy were included. Bayesian processing allowed quantification of collateral perfusion indices like the volume of tissue with severely prolonged arterial-tissue delay (>6 s) (VolATD6). Baseline DWI lesion volume was also measured. Correlations with angiographic collateral flow grading and post-thrombectomy recanalization were assessed. RESULTS VolATD6 < 27 ml or DWI lesion volume <15 ml provide the most accurate diagnosis of excellent collateral supply (p < 0.0001). The combination of VolATD6 > 27 ml and DWI lesion volume >15 ml significantly discriminates recanalizers versus nonrecanalizers (whole cohort, p = 0.032; MERCI cohort (n = 50), p = 0.024). When both criteria are positive, 76.2 % of the patients treated with the MERCI retriever do not fully recanalize (p = 0.024). In multivariate analysis, the aforementioned combined criterion and the angiographic collateral grade are the only independent predictors of recanalization with the MERCI retriever (p = 0.015 and 0.029, respectively). CONCLUSION Bayesian arterial-tissue delay maps and DWI maps provide a non-invasive assessment of the degree of collateral flow and a combined index that is predictive of MCA-M1 recanalization after endovascular thrombectomy. Further studies are needed to evaluate the accuracy of this index in patients treated with novel stent retriever devices.


title: Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression.

text: BACKGROUND Pill-taking, expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder (MDD). Aims To examine the effects of medication, placebo and supportive care on treatment outcome, and the relationships of expectations and therapeutic alliance to improvement. METHOD A total of 88 participants were randomised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication. Expectations of medication effectiveness, general treatment effectiveness and therapeutic alliance were measured (trial registration at ClinicalTrials.gov: NCT00200902). RESULTS Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone. Therapeutic alliance predicted response to medication and placebo; expectations of medication effectiveness at enrolment predicted only placebo response. CONCLUSIONS Pill treatment yielded better outcome than supportive care alone. Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment, suggesting that they were shaped by prior experiences outside the clinical trial.


title: Flow diversion for complex intracranial aneurysms in young children.

text: Pediatric intracranial aneurysms are exceedingly rare and account for less than 5% of all intracranial aneurysms. Open surgery to treat such aneurysms has been shown to be more durable than endovascular techniques, and durability of treatment is particularly important in the pediatric population. Over the past 2 decades, however, a marked shift in aneurysm treatment from open surgery toward endovascular procedures has occurred for adults. The authors describe their early experience in treating 3 unruptured pediatric brain aneurysms using the Pipeline embolization device (PED). The first patient, a girl with Majewski osteodysplastic primordial dwarfism Type II who was harboring multiple intracranial aneurysms, underwent two flow diversion procedures for a vertebrobasilar aneurysm and a supraclinoid internal carotid artery aneurysm. The second patient underwent PED placement on a previously coiled but enlarging posterior communicating artery aneurysm. All procedures were uneventful, with no postsurgical complications, and led to complete angiographic obliteration of the aneurysms. To the authors' knowledge, this is the first series of flow diversion procedures in children reported in the medical literature. While flow diversion is a new and relatively untested technology in children, outcomes in adults have been promising. For challenging lesions in the pediatric population, flow diversion may have a valuable role as a well-tolerated, safe treatment with durable results. Many issues remain to be addressed, such as the durability of flow diverters over a very long follow-up and vessel response to growth in the presence of an endoluminal device.


title: Diagnostic value of drain amylase for detecting intrathoracic leakage after esophagectomy.

text: AIM To investigate the value of elevated drain amylase concentrations for detecting anastomotic leakage (AL) after minimally invasive Ivor-Lewis esophagectomy (MI-ILE). METHODS This was a retrospective analysis of prospectively collected data in two hospitals in the Netherlands. Consecutive patients undergoing MI-ILE were included. A Jackson-Pratt drain next to the dorsal side of the anastomosis and bilateral chest drains were placed at the end of the thoracoscopic procedure. Amylase levels in drain fluid were determined in all patients during at least the first four postoperative days. Contrast computed tomography scans and/or endoscopic imaging were performed in cases of a clinically suspected AL. Anastomotic leakage was defined as any sign of leakage of the esophago-gastric anastomosis on endoscopy, re-operation, radiographic investigations, post mortal examination or when gastro-intestinal contents were found in drain fluid. Receiver operator characteristic curves were used to determine the cut-off values. Sensitivity, specificity, positive predictive value, negative predictive value, risk ratio and overall test accuracy were calculated for elevated drain amylase concentrations. RESULTS A total of 89 patients were included between March 2013 and August 2014. No differences in group characteristics were observed between patients with and without AL, except for age. Patients with AL were older than were patients without AL (P = 0.01). One patient (1.1%) without AL died within 30 d after surgery due to pneumonia and acute respiratory distress syndrome. Anastomotic leakage that required any intervention occurred in 15 patients (16.9%). Patients with proven anastomotic leakage had higher drain amylase levels than patients without anastomotic leakage [median 384 IU/L (IQR 34-6263) vs median 37 IU/L (IQR 26-66), P = 0.003]. Optimal cut-off values on postoperative days 1, 2, and 3 were 350 IU/L, 200 IU/L and 160 IU/L, respectively. An elevated amylase level was found in 9 of the 15 patients with AL. Five of these 9 patients had early elevations of their amylase levels, with a median of 2 d (IQR 2-5) before signs and symptoms occurred. CONCLUSION Measurement of drain amylase levels is an inexpensive and easy tool that may be used to screen for anastomotic leakage soon after MI-ILE. However, clinical validation of this marker is necessary.


title: Vasectomy with vessel sealing device: comparison of different diameters.

text: OBJECTIVES Vasectomy is a popular and effective male surgical contraceptive method. Different techniques have been proposed to reduce failure rates and complications. In this study, we sought to compare vas deferens occlusion rates using both standard occlusion techniques and LigaSure (LSVS) for vasectomy. MATERIAL AND METHODS A total of nine patients underwent open radical retropubic prostatectomy at our institution. During the procedure, a total of 125 fresh vas deferens samples were obtained and divided into four groups as follows: Group 1: ligation (n = 22), Group 2; ligation and electrocauterization (n = 18), Group 3; 5 mm LSVS (n = 44), Group 4; 10 mm LSVS (n = 41). All specimens were harvested during surgery and subsequent histopathological assessments were performed to assess the luminal status of the vas deferens. RESULTS Histopathological evaluation revealed that the majority of vas lumens with LSVS (79.5% of Group 3 and 89.4% of Group 4) were totally occluded. With standard techniques, however, the majority of vas lumens (86.4 and 77.8% of Groups 1 and 2, respectively) maintained a tiny patency. CONCLUSIONS On histopathological review, the application of LSVS resulted in better occlusion rates, compared to standard ligation methods. These findings suggest a higher occlusive role for LSVS for vasectomy. Further clinical studies are needed to confirm the clinical efficacy and safety of this technique.


First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab.


title: Management of Patients With Fever and Neutropenia Through the Arc of Time: A Narrative Review.

text: The association between fever and neutropenia and the risk for life-threatening infections in patients receiving cytotoxic chemotherapy has been known for 50 years. Indeed, infectious complications have been a leading cause of morbidity and mortality in patients with cancer. This review chronicles the progress in defining and developing approaches to the management of fever and neutropenia through observational and controlled clinical trials done by single institutions, as well as by national and international collaborative groups. The resultant data have led to recommendations and guidelines from professional societies and frame the current principles of management. Recommendations include those guiding new treatment options (from monotherapy to oral antibiotic therapy) and use of prophylactic antimicrobial regimens in high-risk patients. Of note, risk factors have changed with the advent of hematopoietic cytokines (especially granulocyte colony-stimulating factor) in shortening the duration of neutropenia, as well as with the discovery of more targeted cancer treatments that do not result in cytotoxicity, although these are still the exception. Most guiding principles that were developed decades ago-about when to begin empirical treatment after a neutropenic patient becomes febrile, whether and how to modify the initial treatment regimen (especially in patients with protracted neutropenia), and how long to continue antimicrobial therapy-are still used today. This review describes how the treatment principles related to the management of fever and neutropenia have responded to changes in the patients at risk, the microbes responsible, and the tools for their treatment, while still being sustained over the arc of time.


title: A new conceptual model of experiences of aging in place in the United States: Results of a systematic review and meta-ethnography of qualitative studies.

text: OBJECTIVES The purpose of this systematic review was to synthesize the evidence on experiences of aging in place in the United States. DESIGN Systematic review and meta-ethnography of qualitative studies. DATA SOURCES We searched six bibliographic databases (PubMed, Embase, PsycINFO, CINAHL, Web of Science, Sociological Abstracts), with no limits on publication date. Eligible studies reported peer-reviewed qualitative research on experiences of aging in place in the United States with full-text available in English. REVIEW METHODS Three reviewers independently used Covidence software to screen titles and abstracts followed by full texts. We assessed quality and risk of bias using a modified version of the Joanna Briggs Institute Checklist for Qualitative Research. Qualitative data analysis was conducted using meta-ethnography, following Noblit and Hare's seven-step method of translation and synthesis to generate a novel conceptual model. RESULTS Of 2659 papers screened, 37 unique studies were eligible for inclusion, reported in 38 publications. The studies were conducted in 16 states and published between 1994 and 2018. The included samples represented 1199 participants in total, with mean ages ranging from 48 to 91 years. The gender of the samples ranged from 20% to 100% female, with a median of 77%. One-third of the included studies did not report participants' race/ethnicity, and half of the remaining study samples were at least 90% white; however, 20% of the studies focused exclusively on experiences of racial/ethnic minority older adults. Using meta-ethnography, we developed a new conceptual model of aging in place in the United States as a dynamic process of balancing threats and agency in relation to experiences of identity, connectedness, and place. We found that people aging in place were engaged in significant work to cope with unpredictable needs and challenges by changing their mindset, adapting their home environment to accommodate new needs, and finding different ways to connect with important people in their lives. Agency was shaped by resources and restrictions on choice, and where threats to aging in place outweighed an individual's sense of agency, the consequences included feelings of uncertainty, isolation, and dislocation. CONCLUSIONS To the best of our knowledge, this is the first systematic review of qualitative studies to evaluate experiences of aging in place in the United States. The findings of our meta-ethnographic synthesis led to the development of a new conceptual model of aging in place highlighting the dynamic tensions involved in balancing threats and agency.


title: Reconstruction of swan neck deformities after proximal interphalangeal joint arthroplasty.

text: BACKGROUND The authors report the use of a single slip of the flexor digitorum superficialis (FDS) as a hemitenodesis through the A2 pulley in treating swan neck deformities after previous unconstrained proximal interphalangeal joint (PIP) arthroplasty. METHODS A retrospective chart review was undertaken to identify non-constrained PIP joint arthroplasties that underwent a subsequent soft tissue hemitenodesis for swan neck deformities. The range of motion (ROM), implant design, preoperative diagnosis, and surgical approach were collected. The Michigan Hand Outcomes Questionnaire and patient satisfaction questionnaire were collected. RESULTS There were 12 patients with 14 procedures reviewed. There were seven surface replacement arthroplasties (SRA) (cobalt chrome on polyethylene) and eight pyrocarbon prostheses. The primary diagnosis for the initial joint arthroplasty was osteoarthritis (8), post-traumatic (2), and rheumatoid arthritis (5). The primary dorsal approach was a longitudinal split in eleven cases, Chamay in two, and unknown in one case. Nine of the 14 revision procedures had a concomitant dorsal approach to the joint. The average final position intraoperatively was 24.2° of flexion (range 15°-40°). Final ROM was 39° with average follow-up of 30 months. The average postoperative radiographic position was 20.3° flexion with an average of 24.8° hyperextension preoperatively. There was one failure secondary to implant loosening requiring fusion. DISCUSSION For patients with a swan neck deformity after PIP arthroplasty, a FDS hemitenodesis provides a treatment option with a low revision rate, retained motion, and maintenance of the original implant with no shortening of the digit.


title: Risk factors for new-onset atrial fibrillation on the general adult ICU: protocol for a systematic review.

text: INTRODUCTION Atrial fibrillation (AF) is a common arrhythmia in the critical care environment. New-onset AF is associated with increased mortality and intensive care unit (ICU) length of stay. Observational studies have identified several epidemiological and disease severity-related factors associated with developing new-onset AF on the ICU. However, there are limited data on the modifiable risk factors in the general adult ICU population.We describe a protocol for a systematic review of modifiable and non-modifiable risk factors for new-onset AF in the general adult ICU population. The results of this review will aid the development of risk prediction tools and inform future research into AF prevention on the ICU. METHODS AND ANALYSIS Medical Literature Analysis and Retrieval System Online, Excerpta Medica database and the Cochrane Library, including Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials will be searched for studies that assess the association of patient variables, investigation results, interventions and diagnoses associated with subsequent new-onset AF on the ICU.Only studies involving adult patients admitted to non-service-specific ICUs will be included. We will extract data relating to the statistical association between reversible and non-reversible factors and AF, the quality of the studies and the generalisability of the results. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. ETHICS AND DISSEMINATION This proposed systematic review will be based on published data, and therefore ethical approval is not required. The findings of this study will be disseminated through publication in a peer reviewed journal and will be presented at conferences. PROSPERO REGISTRATION NUMBER CRD42017074221.


title: Liberal Manipulation of Ventilator Settings and Its Impact on Tracheostomy Rate and Ventilator-Free Days.

text: BACKGROUND The utilization of checklists, bundles, and protocols attempts to provide standardization in the delivery of patient care. Despite important progress obtained in the prevention of hospital-acquired infections, the daily management of mechanical ventilation is still prone to heterogeneity, depending on the number of providers manipulating the ventilator. Whether the number of changes made on ventilator parameters impacts clinical outcomes remains unknown. METHODS A quality improvement project was designed to assess whether liberal manipulations of ventilator settings affect the rate of tracheostomy and 28 ventilator-free days. Over the course of 7 d, respiratory therapists recorded all ventilator changes in newly ventilated subjects. Ventilator changes were considered as major changes if manipulations included changes in the mode of ventilation. Minor changes included manipulations of settings within the same mode of ventilation. We evaluated whether the number of total and major changes affected clinical outcomes. Logistic regression was used for multivariate analysis. RESULTS One-hundred seventeen ventilator manipulations were recorded among 54 subjects. Of those 117 ventilator changes, 35% were major manipulations. For every major ventilator manipulation, the odds of requiring tracheostomy increased 4.95 times. Furthermore, for every major ventilator change, there was an 18.6% decrease in 28 ventilator-free days. These associations were found after adjustments by APACHE (Acute Physiology and Chronic Health Evaluation) II score, body mass index, and type of ICU. The total number of changes was not associated with either primary outcome measure. CONCLUSIONS The number of major ventilator manipulations is associated with rate of tracheostomy and stay on the ventilator.


title: Early mobilizing and dangling of the lower leg after one-stage reconstruction of Achilles tendon and overlying tissue defect using an anterolateral thigh flap with vascularized fascia lata.

text: We have treated two patients who had an Achilles tendon and overlying tissue defect using an anterolateral thigh flap with fascia lata. Postoperatively, skeletal suspension of the affected leg and intra-arterial heparin infusion were performed for seven days. Six weeks postoperatively, the patients could walk again.


title: The neck region of the C-type lectin DC-SIGN regulates its surface spatiotemporal organization and virus-binding capacity on antigen-presenting cells.

text: The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and role in viral binding remain enigmatic. By combining biochemical and advanced biophysical techniques, including optical superresolution and single particle tracking, we demonstrate that DC-SIGN intrinsic nanoclustering strictly depends on its molecular structure. DC-SIGN nanoclusters exhibited free, Brownian diffusion on the cell membrane. Truncation of the extracellular neck region, known to abrogate tetramerization, significantly reduced nanoclustering and concomitantly increased lateral diffusion. Importantly, DC-SIGN nanocluster dissolution exclusively compromised binding to nanoscale size pathogens. Monte Carlo simulations revealed that heterogeneity on nanocluster density and spatial distribution confers broader binding capabilities to DC-SIGN. As such, our results underscore a direct relationship between spatial nanopatterning, driven by intermolecular interactions between the neck regions, and receptor diffusion to provide DC-SIGN with the exquisite ability to dock pathogens at the virus length scale. Insight into how virus receptors are organized prior to virus binding and how they assemble into functional platforms for virus docking is helpful to develop novel strategies to prevent virus entry and infection.


title: Selection of naturally occurring autoantibodies to interleukin-18 from phage display library.

text: Four unique phage single-chain variable fragments (scFvs) to recombinant human interleukin 18 (IL-18) has been selected from a naïve combinatorial library of human scFvs. Binding of unique phage antibodies with IL-18 was tested by ELISA and Western-blotting. No cross reactivity with tumor necrosis factor α, interferons α and γ was shown for the selected antibodies. The gene segments encoding V(D)J regions of selected antibodies exhibited a high degree of homology to germline genes, therefore we suggest that the selected scFv's belong to repertoire of naïve autoantibodies.


title: Effectiveness of ovarian suspension in preventing post-operative ovarian adhesions in women with pelvic endometriosis: a randomised controlled trial.

text: BACKGROUND Endometriosis is a common benign condition, which is characterized by the growth of endometrial-like tissue in ectopic sites outside the uterus. Laparoscopic excision of the disease is frequently carried out for the treatment of severe endometriosis. Pelvic adhesions often develop following surgery and they can compromise the success of treatment. Ovarian suspension (elevating both ovaries to the anterior abdominal wall using a Prolene suture) is a simple procedure which has been used to facilitate ovarian retraction during surgery for severe pelvic endometriosis. The study aims to assess the effect of temporary ovarian suspension following laparoscopic surgery for severe pelvic endometriosis on the prevalence of post-operative ovarian adhesions. METHODS A prospective double blind randomised controlled trial for patients with severe pelvic endometriosis requiring extensive laparoscopic dissection with preservation of the uterus and ovaries. Severity of the disease and eligibility for inclusion will be confirmed at surgery. Patients unable to provide written consent, inability to tolerate a transvaginal ultrasound scan, unsuccessful surgeries or suffer complications leading to oophorectomies, bowel injuries or open surgery will be excluded. Both ovaries are routinely suspended to the anterior abdominal wall during surgery. At the end of the operation, each participant will be randomised to having only one ovary suspended post-operatively. A new transabdominal suture will be reinserted to act as a placebo. Both sutures will be cut 36 to 48 hours after surgery before the woman is discharged home. Three months after surgery, all randomised patients will have a transvaginal ultrasound scan to assess for ovarian mobility. Both the patients and the person performing the scan will be blinded to the randomisation process. The primary outcome is the prevalence of ovarian adhesions on ultrasound examination. Secondary outcomes are the presence, intensity and site of post-operative pain. DISCUSSION This controlled trial will provide evidence as to whether temporary ovarian suspension should be included into the routine surgical treatment of women with severe pelvic endometriosis. TRIAL REGISTRATION ISRCTN: ISRCTN24242218.


title: Next science wound gel technology, a novel agent that inhibits biofilm development by gram-positive and gram-negative wound pathogens.

text: Loss of the skin barrier facilitates the colonization of underlying tissues with various bacteria, where they form biofilms that protect them from antibiotics and host responses. Such wounds then become chronically infected. Topical antimicrobials are a major component of chronic wound therapy, yet currently available topical antimicrobials vary in their effectiveness on biofilm-forming pathogens. In this study, we evaluated the efficacy of Next Science wound gel technology (NxtSc), a novel topical agent designed to kill planktonic bacteria, penetrate biofilms, and kill the bacteria within. In vitro quantitative analysis, using strains isolated from wounds, showed that NxtSc inhibited biofilm development by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae by inhibiting bacterial growth. The gel formulation NxtSc-G5, when applied to biofilms preformed by these pathogens, reduced the numbers of bacteria present by 7 to 8 log10 CFU/disc or CFU/g. In vivo, NxtSc-G5 prevented biofilm formation for 72 h when applied at the time of wounding and infection and eliminated biofilm infection when applied 24 h after wounding and infection. Storage of NxtSc-G5 at room temperature for 9 months did not diminish its efficacy. These results establish that NxtSc is efficacious in vitro and in vivo in preventing infection and biofilm development by different wound pathogens when applied immediately and in eliminating biofilm infection already established by these pathogens. This novel antimicrobial agent, which is nontoxic and has a usefully long shelf life, shows promise as an effective agent for the prevention and treatment of biofilm-related infections.


title: Use of MIRUS™ for MAC-driven application of isoflurane, sevoflurane, and desflurane in postoperative ICU patients: a randomized controlled trial.

text: BACKGROUND The MIRUS™ (TIM, Koblenz, Germany) is an electronical gas delivery system, which offers an automated MAC (minimal alveolar concentration)-driven application of isoflurane, sevoflurane, or desflurane, and can be used for sedation in the intensive care unit. We investigated its consumption of volatile anesthetics at 0.5 MAC (primary endpoint) and the corresponding costs. Secondary endpoints were the technical feasibility to reach and control the MAC automatically, the depth of sedation at 0.5 MAC, and awakening times. Mechanically ventilated and sedated patients after major surgery were enrolled. Upon arrival in the intensive care unit, patients obtained intravenous propofol sedation for at least 1 h to collect ventilation and blood gas parameters, before they were switched to inhalational sedation using MIRUS™ with isoflurane, sevoflurane, or desflurane. After a minimum of 2 h, inhalational sedation was stopped, and awakening times were recorded. A multivariate electroencephalogram and the Richmond Agitation Sedation Scale (RASS) were used to assess the depth of sedation. Vital signs, ventilation parameters, gas consumption, MAC, and expiratory gas concentrations were continuously recorded. RESULTS Thirty patients obtained inhalational sedation for 18:08 [14:46-21:34] [median 1st-3rd quartiles] hours. The MAC was 0.58 [0.50-0.64], resulting in a Narcotrend Index of 37.1 [30.9-42.4] and a RASS of - 3.0 [- 4.0 to (- 3.0)]. The median gas consumption was significantly lowest for isoflurane ([ml h-1]: isoflurane: 3.97 [3.61-5.70]; sevoflurane: 8.91 [6.32-13.76]; and desflurane: 25.88 [20.38-30.82]; p < 0.001). This corresponds to average costs of 0.39 € h-1 for isoflurane, 2.14 € h-1 for sevoflurane, and 7.54 € h-1 for desflurane. Awakening times (eye opening [min]: isoflurane: 9:48 [4:15-20:18]; sevoflurane: 3:45 [0:30-6:30]; desflurane: 2:00 [1:00-6:30]; p = 0.043) and time to extubation ([min]: isoflurane: 10:10 [8:00-20:30]; sevoflurane: 7:30 [4:37-14:22]; desflurane: 3:00 [3:00-6:00]; p = 0.007) were significantly shortest for desflurane. CONCLUSIONS A target-controlled, MAC-driven automated application of volatile anesthetics is technically feasible and enables an adequate depth of sedation. Gas consumption was highest for desflurane, which is also the most expensive volatile anesthetic. Although awakening times were shortest, the actual time saving of a few minutes might be negligible for most patients in the intensive care unit. Thus, using desflurane seems not rational from an economic perspective. Trial registration Clinical Trials Registry (ref.: NCT03860129). Registered 24 September 2018-Retrospectively registered.


[The role of speech in the transmission of SARSCoV-2: recommendations for confined spaces].


Should patients starting biologics be screened for COVID-19?


title: Clinical Experience with the PillCam Patency Capsule prior to Video Capsule Endoscopy: A Real-World Experience.

text: Background. In patients with known or suspected risk factors for gastrointestinal stenosis, the PillCam patency capsule (PC) is given before a video capsule endoscopy (VCE) in order to minimize the risk of capsule retention (CR). CR is considered unlikely upon excretion of the PC within 30 hours, excretion in an undamaged state after 30 hours, or radiological projection to the colon. Methods. We performed a retrospective analysis of 38 patients with risk factors for CR, who received a PC from 02/2013 to 04/2015 at Klinikum Augsburg. Results. Sixteen of our 38 patients observed a natural excretion after a mean time of 34 hours past ingestion. However, only 8 patients observed excretion within 30 hours, as recommended by the company. In 20 patients passage of the PC into the colon was shown via RFID-scan or radiological imaging (after 33 and 45 hours, resp.). Only 2 patients showed a pathologic PC result. In consequence, 32 patients received the VCE; no CR was observed. Conclusion. Our data indicates that a VCE could safely be performed even if the PC excretion time is longer than 30 hours and the excreted PC was not screened for damage.


Prioritising paediatric surveillance during the COVID-19 pandemic.


title: Temporary distal balloon occlusion for hepatic embolization: a novel technique to treat what cannot be selected.

text: PURPOSE Particle embolotherapy for liver cancers, such as chemoembolization and yttrium-90 radioembolization, depends on microcatheter selection of the treatment vessel for injection of the embolic. Individually selecting vessels with a microcatheter can be time-consuming and difficult, especially when multiple branches are present in the treatment zone. This article describes a technique to perform an "inverse" embolization-protection of the selected vessel and embolization of the unselected vessels-a technique that has not yet been described. MATERIALS AND METHODS Two cases of hepatic chemoembolization that would require subselection of multiple branch vessels using conventional technique are reported. In both cases the proper hepatic artery was selected with a soft, nondissecting neurovascular guide catheter. The nontarget hepatic vessel was selected with a neurovascular microcatheter occlusion balloon, and the balloon was inflated to protect that vessel. Embolization to multiple target vessels was then achieved by way of a single injection through the guide catheter. RESULTS Both procedures were technically successful without complication. Postembolization angiography confirmed normal parenchymal enhancement in the protected zone and expected paucity of enhancement in the treated zone. CONCLUSION Temporary distal balloon occlusion is a useful technique to treat multiple artery branches with a single injection in cases where individual selection of the branches is difficult or time-consuming. Further study of this technique is warranted.


title: Investigating an outbreak of acute fever in Chuuk, Federated States of Micronesia.

text: OBJECTIVE In September 2012, there was an unexpected increase of acute febrile illness (AFI) in Chuuk State of the Federated States of Micronesia. At the same time, dengue outbreaks were occurring in two of the Federated States of Micronesia's other three states. The cause of AFI was suspected to be dengue; however, by the end of October, only one of 39 samples was positive for dengue. The objective of the investigation was to establish the cause of the outbreak. METHODS A line list was created and data analysed by time, place, person and clinical features. Reported symptoms were compared with the published symptoms of several diagnoses and laboratory testing undertaken. RESULTS Of the 168 suspected cases, 62% were less than 20 years of age and 60% were male. The clinical features of the cases were not typical for dengue but suggestive of respiratory illness. Nasopharyngeal swabs were subsequently collected and found to be positive for influenza. Public health measures were undertaken and the AFI returned to expected levels. DISCUSSION Clinical diagnosis of acute febrile illness (AFI) can often be difficult and misleading. This can mean that opportunities for preventive measures early on in an outbreak are missed. In any outbreak, descriptive epidemiological analyses are valuable in helping to ascertain the cause of the outbreak.


title: Three-dimensional quantitative assessment of ablation margins based on registration of pre- and post-procedural MRI and distance map.

text: PURPOSE Contrast-enhanced MR images are widely used to confirm the adequacy of ablation margin after liver ablation for early prediction of local recurrence. However, quantitative assessment of the ablation margin by comparing pre- and post-procedural images remains challenging. We developed and tested a novel method for three-dimensional quantitative assessment of ablation margin based on non-rigid image registration and 3D distance map. METHODS Our method was tested with pre- and post-procedural MR images acquired in 21 patients who underwent image-guided percutaneous liver ablation. The two images were co-registered using non-rigid intensity-based registration. After the tumor and ablation volumes were segmented, target volume coverage, percent of tumor coverage, and Dice similarity coefficient were calculated as metrics representing overall adequacy of ablation. In addition, 3D distance map around the tumor was computed and superimposed on the ablation volume to identify the area with insufficient margins. For patients with local recurrences, the follow-up images were registered to the post-procedural image. Three-dimensional minimum distance between the recurrence and the areas with insufficient margins was quantified. RESULTS The percent tumor coverage for all nonrecurrent cases was 100 %. Five cases had tumor recurrences, and the 3D distance map revealed insufficient tumor coverage or a 0-mm margin. It also showed that two recurrences were remote to the insufficient margin. CONCLUSIONS Non-rigid registration and 3D distance map allow us to quantitatively evaluate the adequacy of the ablation margin after percutaneous liver ablation. The method may be useful to predict local recurrences immediately following ablation procedure.


title: Faster recovery of gastrointestinal transit after laparoscopy and fast-track care in patients undergoing colonic surgery.

text: BACKGROUND & AIMS Postoperative ileus is characterized by delayed gastrointestinal (GI) transit and is a major determinant of recovery after colorectal surgery. Both laparoscopic surgery and fast-track multimodal perioperative care have been reported to improve clinical recovery. However, objective measures supporting faster GI recovery are lacking. Therefore, GI transit was measured following open and laparoscopic colorectal surgery with or without fast-track care. METHODS Patients (n = 93) requiring elective colonic surgery were randomized to laparoscopic or conventional surgery with fast-track multimodal management or standard care, resulting in 4 treatment arms. Gastric emptying and colonic transit were scintigraphically assessed from days 1 to 3 in 78 patients and compared with clinical parameters such as time to tolerance of solid food and/or bowel movement and time until (ready for) discharge. RESULTS A total of 71 patients without mechanical bowel obstructions or surgical complications requiring intervention were available for analysis. No differences in gastric emptying 24 hours after surgery between the different groups were observed (P = .61). However, the median colonic transit of patients undergoing laparoscopic/fast-track care was significantly faster compared with the laparoscopic/standard, open/fast-track, and open/standard care groups. Multiple linear regression analysis showed that both laparoscopic surgery and fast-track care were significant independent predictive factors of improved colonic transit. Both were associated with significantly faster clinical recovery and shorter time until tolerance of solid food and first bowel movement. CONCLUSIONS Colonic transit recovers significantly faster after laparoscopic surgery and the fast-track program; laparoscopy and fast-track care lead to faster recovery of GI motility and improve clinical recovery.


title: Robotic Enucleation for Benign or Borderline Tumours of the Pancreas: A Retrospective Analysis and Comparison from a High-Volume Centre in Asia.

text: BACKGROUND Enucleation is increasingly performed for benign or borderline tumours of the pancreas because it is a parenchyma-sparing and less invasive procedure compared to conventional pancreatectomy, which reduces the risk of exocrine and endocrine insufficiency. This study retrospectively evaluated and compared the pre-, intra-, and post-operative clinical characteristics after open and robotic approaches for pancreatic enucleation. METHODS Fifty-six cases of enucleation for benign or borderline tumours of the pancreas treated from March 2010 to July 2015 were identified by a retrospective search. These included 25 patients who underwent an open approach and 31 patients who underwent a robotic approach. The clinical characteristics were extracted and compared. RESULTS The two groups had a similar location and pathology of the tumour. The robotic group had a significantly shorter operation time and significantly less blood loss than the open group. The rates of clinical pancreatic fistula (PF) formation and major complications were similar. The robotic approach could be applied for a tumour on the right side of the pancreas without increasing the incidence of clinical PF or other major complications. The patients with clinical PF had a significantly shorter distance between the lesion and the main pancreatic duct (MPD). CONCLUSION Robotic enucleation appears to be a feasible and safe approach for benign or borderline tumours of the pancreas and was associated with similarly favourable surgical outcomes as the open approach. Identifying and avoiding the MPD is an important step during enucleation.


title: Artificial Intelligence and the Future of Psychiatry.

text: An estimated 792 million people live with mental health disorders worldwide-more than one in ten people-and this number is expected to grow in the shadow of the Coronavirus disease 2019 (COVID-19) pandemic. Unfortunately, there aren't enough mental health professionals to treat all these people. Can artificial intelligence (AI) help? While many psychiatrists have different views on this question, recent developments suggest AI may change the practice of psychiatry for both clinicians and patients.


title: Genome-wide analysis of long noncoding RNA profiles in Vero cells infected with porcine epidemic diarrhea virus.

text: Porcine epidemic diarrhea (PED) is an acute enteric disease caused by porcine epidemic diarrhea virus (PEDV). In China, variant PEDV causes severe watery diarrhea, vomiting, and dehydration in piglets, leading to very high morbidity and mortality. However, the pathogenesis of PEDV is still not fully understood. In our study, we analyzed the long noncoding RNA (lncRNA) and mRNA expression profiles of PEDV GDgh16 in infected Vero cells at 60 h postinfection. A total of 61,790 annotated mRNAs, 14,247 annotated lncRNAs and 1290 novel lncRNAs were identified. A total of 227 annotated lncRNAs and 13 novel lncRNAs were significantly and differentially expressed after viral infection. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used to identify genes adjacent to the lncRNAs, and it was found that these lncRNAs were enriched in pathways related to immune and antiviral responses. Next, we selected candidate lncRNAs and their predicted target genes for study. RT-qPCR demonstrated that these lncRNAs and genes were differentially expressed after PEDV infection. Our study investigated the function of lncRNAs involved in PEDV infection, providing new insight into the pathogenic mechanisms of PEDV.


title: Far from Home.

text: A flight nurse cares for one of COVID-19's many 'peripheral victims.'


Case scenario: power of positive end-expiratory pressure: use of esophageal manometry to illustrate pulmonary physiology in an obese patient.


The C-MAC(®) D-BLADE™: use of the guide rail as a guiding channel for a gum elastic bougie.


title: Bispectral index guided titration of sevoflurane in on-pump cardiac surgery reduces plasma sevoflurane concentration and vasopressor requirements: a prospective, controlled, sequential two-arm clinical study.

text: BACKGROUND Electroencephalographic-based monitoring systems such as the bispectral index (BIS) may reduce anaesthetic overdose rates. OBJECTIVE We hypothesised that goal-directed sevoflurane administration (guided by BIS monitoring) could reduce the sevoflurane plasma concentration (SPC) and intraoperative vasopressor doses during on-pump cardiac surgery. DESIGN A prospective, controlled, sequential two-arm clinical study. SETTING German university medical centre with more than 2500 cardiac surgery interventions per year. PATIENTS Sixty elective on-pump cardiac surgery patients. INTERVENTION In group Sevo1.8% (n = 29), the sedation depth was maintained with a sustained inspired concentration of sevoflurane 1.8% before and during cardiopulmonary bypass (CPB). In group SevoBIS (n = 31), the inspired sevoflurane concentration was titrated to maintain a BIS target between 40 and 60. OUTCOME MEASURES SPC during CPB and the intraoperative administration of noradrenaline. Additional analyses were performed on intraoperative awareness, postoperative blood lactate concentration, duration of mechanical ventilation, intensive care unit length of stay and kidney injury. RESULTS Mean inspired sevoflurane concentration was 0.8% in group SevoBIS, representing a 57.1% reduction (P < 0.001) compared with group Sevo1.8%. The mean SPC was 42.3 μg ml(-1) [95% confidence interval (CI) 40.0 to 44.6] in group Sevo1.8% and 21.0 μg ml(-1) (95% CI 18.8 to 23.3) in group SevoBIS, representing a 50.2% reduction (P < 0.001). During CPB, the mean cumulative dose of noradrenaline administered was 13.48 μg kg(-1) (95% CI 10.52 to 17.19) in group Sevo1.8% and 4.06 μg kg(-1) (95% CI 2.67 to 5.97) in group SevoBIS (P < 0.001). Pearson's correlation coefficient (between the cumulative applied dosage of sevoflurane calculated from the area under the curve of the SPC over time and the administered cumulative noradrenaline dose) was 0.607 (P < 0.001). No intraoperative awareness signs were detected. CONCLUSION BIS-guided titration of sevoflurane reduces the SPC and decreases noradrenaline administration compared with routine care during on-pump cardiac surgery.


title: A Reverse-Transcription Recombinase-Aided Amplification Assay for Rapid Detection of the 2019 Novel Coronavirus (SARS-CoV-2).

text: A novel coronavirus (SARS-CoV-2) was recently identified in patients with acute respiratory disease and spread quickly worldwide. A specific and rapid diagnostic method is important for early identification. The reverse-transcription recombinase-aided amplification (RT-RAA) assay is a rapid detection method for several pathogens. Assays were performed within 5-15 min as a one-step single tube reaction at 39 °C. In this study, we established two RT-RAA assays for the S and orf1ab gene of SARS-CoV-2 using clinical specimens for validation. The analytical sensitivity of the RT-RAA assay was 10 copies for the S and one copy for the orf1ab gene per reaction. Cross-reactions were not observed with any of the other respiratory pathogens. A hundred percent agreement between the RT-RAA and real-time PCR assays was accomplished after testing 120 respiratory specimens. These results demonstrate that the proposed RT-RAA assay will be beneficial as it is a faster, more sensitive, and more specific tool for the detection of SARS-CoV-2.


title: Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus, and infections with this virus can result in acute respiratory syndrome with renal failure. Globally, MERS-CoV has been responsible for 877 laboratory-confirmed infections, including 317 deaths, since September 2012. As there is a paucity of information regarding the molecular pathogenesis associated with this virus or the identities of novel antiviral drug targets, we performed temporal kinome analysis on human hepatocytes infected with the Erasmus isolate of MERS-CoV with peptide kinome arrays. bioinformatics analysis of our kinome data, including pathway overrepresentation analysis (ORA) and functional network analysis, suggested that extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling responses were specifically modulated in response to MERS-CoV infection in vitro throughout the course of infection. The overrepresentation of specific intermediates within these pathways determined by pathway and functional network analysis of our kinome data correlated with similar patterns of phosphorylation determined through Western blot array analysis. In addition, analysis of the effects of specific kinase inhibitors on MERS-CoV infection in tissue culture models confirmed these cellular response observations. Further, we have demonstrated that a subset of licensed kinase inhibitors targeting the ERK/MAPK and PI3K/AKT/mTOR pathways significantly inhibited MERS-CoV replication in vitro whether they were added before or after viral infection. Taken together, our data suggest that ERK/MAPK and PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and may represent novel drug targets for therapeutic intervention strategies.


title: Endovascular therapy for critical limb ischemia.

text: Critical limb ischemia (CLI) represents an advanced disease state of peripheral arterial disease. It manifests as lower extremity ischemic rest pain or ischemic skin lesions leading to ulceration or gangrene. Patients with CLI often have multiple medical comorbidities and a 1-year mortality rate of 25% and a 1-year amputation rate of 25%. Historically, bypass surgery with autogenous veins for flow restoration has been the first-line therapy for CLI. However, advances in endovascular techniques and device technology have changed the treatment paradigm. Catheter-based technologies are rapidly evolving at a rate that is outpacing large-scale studies evaluating relevant clinical outcomes. Patients with CLI require a multidisciplinary management approach centered on aggressive medical therapies, wound care and prompt revascularization, with an emphasis on limb salvage. This review summarizes the contemporary endovascular therapies including balloon angioplasty, atherectomy and bare-metal stenting. In addition, we review emerging technologies, such as drug-eluting stents, drug-coated balloons and chronic total occlusion recanalization devices.


title: Prevention of nosocomial infections in the intensive care unit.

text: Infections are considered nosocomial if they occur 48 hours or more after hospital admission or within 30 days after discharge. One third of these infections are considered preventable. Many studies have shown that with proper education and use of strict guidelines, we can prevent nosocomial infections in the intensive care unit. In this article, we will review the literature on preventing catheter-associated urinary tract infection, central line-associated blood stream infection, and ventilator-associated pneumonia.


title: Perioperative Complications and Outcome of Laparoscopic Cholecystectomy in 20 Dogs.

text: OBJECTIVE To report the complications and outcome of dogs undergoing laparoscopic cholecystectomy for uncomplicated gall bladder disease. STUDY DESIGN Multi-institutional case series. ANIMALS Client-owned dogs (n=20). METHODS Medical records of dogs that underwent laparoscopic cholecystectomy were reviewed and signalment, history, clinical and ultrasound examination findings, surgical variables, and complications were collated. Laparoscopic cholecystectomy was performed using a multiport approach. Data were compared between dogs with successful laparoscopic cholecystectomy and dogs requiring conversion to open cholecystectomy. RESULTS Six dogs (30%) required conversion from laparoscopic to open cholecystectomy due to inability to ligate the cystic duct (3), evidence of gall bladder rupture (1), leakage from the cystic duct during dissection (1), and cardiac arrest (1). Cystic duct dissection was performed in 19 dogs using an articulating dissector (10), right angle forceps (7), and unrecorded (2). The cystic duct was ligated in 15 dogs using surgical clips (5), suture (6), or a combination (4). All dogs were discharged from the hospital and had resolution of clinical signs, although 1 dog developed pancreatitis and 1 dog required revision surgery for bile peritonitis. There was no significant difference in preoperative blood analysis results, surgical technique, or duration of hospitalization between dogs undergoing laparoscopic cholecystectomy and cases converted to open cholecystectomy. CONCLUSION Laparoscopic cholecystectomy can be performed successfully for uncomplicated gall bladder disease in dogs after careful case selection. The surgeon considering laparoscopic cholecystectomy should be familiar with a variety of methods for cystic duct dissection and ligation to avoid difficulties during the procedure.


title: Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy.

text: OBJECTIVES In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. DESIGN Post hoc analysis of a randomized clinical trial. SETTING Twenty-three ICUs. PATIENTS Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg. INTERVENTION Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. MEASUREMENT AND MAIN RESULTS Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13-6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a PaO2/FIO2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62-11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22-8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality. CONCLUSIONS In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A PaO2/FIO2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.


African nations missing from coronavirus trials.


title: COVID-19, frailty and long-term care: Implications for policy and practice.

text: Older adults have been disproportionately affected by the COVID-19 pandemic, with many outbreaks occurring in Long Term Care Facilities (LTCFs). We discuss this vulnerability among LTCF residents using an ecological framework, on levels spanning from the individual to families and caregivers, institutions, health services and systems, communities, and contextual government policies. Challenges abound for fully understanding the burden of COVID-19 in LTCF, including differences in nomenclature, data collection systems, cultural differences, varied social welfare models, and (often) under-resourcing of the LTC sector. Registration of cases and deaths may be limited by testing capacity and policy, record-keeping and reporting procedures. Hospitalization and death rates may be inaccurate depending on atypical presentations and whether or not residents' goals of care include escalation of care and transfer to hospital. Given the important contribution of frailty, use of the Clinical Frailty Scale (CFS) is discussed as a readily implementable measure, as are lessons learned from the study of frailty in relation to influenza. Biomarkers hold emerging promise in helping to predict disease severity and address the puzzle of why some frail LTCF residents are resilient to COVID-19, either remaining test-negative despite exposure or having asymptomatic infection, while others experience the full range of illness severity including critical illness and death. Strong and coordinated surveillance and research focused on LTCFs and their frail residents is required. These efforts should include widespread assessment of frailty using feasible and readily implementable tools such as the CFS, and rigorous reporting of morbidity and mortality in LTCFs.


Stopping the Gaps in Epidemic Preparedness.


title: Radiofrequency ablation for gastric antral vascular ectasia and radiation proctitis.

text: Gastric antral vascular ectasia (GAVE) and chronic radiation proctitis (CRP) are well-known causes of repeated gastrointestinal bleeding and iron deficiency anemia. Argon plasma coagulation (APC) is the most common endoscopic therapy used, but some patients need multiple APC sessions. Radiofrequency ablation (RFA) is recently used in GAVE and CRP treatment with promising results. In this case series, we analyzed data for 15 patients with GAVE and 5 patients with CRP that had multiple prior APC treatment. They were treated with RFA HALO 90 catheter (HALO90 Ablation Catheter System; Covidien, GI Solutions, Sunnyvale, CA) in our tertiary referral center. A total of 20 patients received 32 RFA procedures (8 in the CRP group and 24 in the GAVE group). The median number of the procedures was 2 (range 1-4). The hemoglobin levels in the GAVE group were 83 g/L pre-RFA and 98 g/L post-RFA and in the CRP group, 86 g/L pre-RFA and 103 g/L post-RFA. A total of 16/20 patients (80%) were transfusion-free after the completion of RFA treatment. Technical success of the treatment was 95% (19/20 patients). RFA can be safely and successfully used in APC refractory GAVE and CRP patients.


title: Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor.

text: UNLABELLED Previous studies in our laboratory have identified equine CXCL16 (EqCXCL16) to be a candidate molecule and possible cell entry receptor for equine arteritis virus (EAV). In horses, the CXCL16 gene is located on equine chromosome 11 (ECA11) and encodes a glycosylated, type I transmembrane protein with 247 amino acids. Stable transfection of HEK-293T cells with plasmid DNA carrying EqCXCL16 (HEK-EqCXCL16 cells) increased the proportion of the cell population permissive to EAV infection from <3% to almost 100%. The increase in permissiveness was blocked either by transfection of HEK-EqCXCL16 cells with small interfering RNAs (siRNAs) directed against EqCXCL16 or by pretreatment with guinea pig polyclonal antibody against EqCXCL16 protein (Gp anti-EqCXCL16 pAb). Furthermore, using a virus overlay protein-binding assay (VOPBA) in combination with far-Western blotting, gradient-purified EAV particles were shown to bind directly to the EqCXCL16 protein in vitro. The binding of biotinylated virulent EAV strain Bucyrus at 4°C was significantly higher in HEK-EqCXCL16 cells than nontransfected HEK-293T cells. Finally, the results demonstrated that EAV preferentially infects subpopulations of horse CD14(+) monocytes expressing EqCXCL16 and that infection of these cells is significantly reduced by pretreatment with Gp anti-EqCXCL16 pAb. The collective data from this study provide confirmatory evidence that the transmembrane form of EqCXCL16 likely plays a major role in EAV host cell entry processes, possibly acting as a primary receptor molecule for this virus. IMPORTANCE Outbreaks of EVA can be a source of significant economic loss for the equine industry from high rates of abortion in pregnant mares, death in young foals, establishment of the carrier state in stallions, and trade restrictions imposed by various countries. Similar to other arteriviruses, EAV primarily targets cells of the monocyte/macrophage lineage, which, when infected, are believed to play a critical role in EVA pathogenesis. To this point, however, the host-specified molecules involved in EAV binding and entry into monocytes/macrophages have not been identified. Identification of the cellular receptors for EAV may provide insights to design antivirals and better prophylactic reagents. In this study, we have demonstrated that EqCXCL16 acts as an EAV entry receptor in EAV-susceptible cells, equine monocytes. These findings represent a significant advance in our understanding of the fundamental mechanisms associated with the entry of EAV into susceptible cells.


title: Biotreatment and bacterial succession in an upflow immobilized cell bioreactor fed with fludioxonil wastewater.

text: The large quantities and the persistent nature of fungicide wastewaters have increased the efforts towards a sustainable technological solution. In this context, fludioxonil-contaminated wastewater was treated in an upflow immobilized cell bioreactor, resulting in chemical oxygen demand (COD) removal efficiency even higher than 80%, whereas the electrical conductivity (EC) of the effluent was gradually increased. Organic-F was mineralized by 94.0 ± 5.2%, which was in accordance with the high fludioxonil removal efficiency (95.4 ± 4.0%). In addition, effluent total Kjeldahl nitrogen (TKN) concentration reduced significantly during bioprocessing. A strong relationship among COD removal, TKN/total nitrogen removal, and effluent EC increase (p < 0.01) was identified. Despite the adequate aeration provided, effluent nitrite and nitrate concentrations were negligible. Illumina sequencing revealed a reduction in the relative abundances of Betaproteobacteria, Chloroflexi, Planctomycetes, and Firmicutes and an increase in the proportion of Alphaproteobacteria and Actinobacteria. A shift in bacterial communities occurred during fludioxonil treatment, resulting in the significant increase of the relative abundances of Empedobacter, Sphingopyxis, and Rhodopseudomonas (from 0.67 ± 0.13% at the start-up to 34.34 ± 1.60% at the end of biotreatment). In conclusion, the immobilized cell bioreactor permitted the proliferation of specialized activated sludge microbiota with an active role in the depuration of postharvest fungicides.


title: Salvage TME following TEM: a possible indication for TaTME.

text: BACKGROUND Salvage surgery after transanal endoscopic microsurgery (TEM) has shown mixed results. Transanal total mesorectal excision (TaTME) might be advantageous in this population. The aim of this study was to assess the short-term oncologic and operative outcomes of salvage surgery after TEM, comparing TaTME to conventional salavge TME (sTME). METHODS Consecutive patients treated with salvage surgery after TEM were identified. Patients who underwent TaTME were compared to those who had conventional sTME. The primary outcome was the ability to perform an appropriate oncologic procedure defined by a composite outcome (negative distal margins, negative radial margins and complete or near complete mesorectum specimen). RESULTS During the study period, 41 patients had salvage surgery after TEM. Of those, 11 patients had TaTME while 30 patients had sTME. All patients in the TaTME group met the composite outcome of appropriate oncologic procedure compared to 76.7% for the conventional sTME group (p = 0.19). TaTME was associated with significantly higher rates of sphincter preservation (100 vs. 50%, p = 0.01), higher rates of laparoscopic surgery (100 vs. 23.3%, p < 0.001) and lower rates of conversion to open surgery (9.1 vs. 57%, p < 0.001). No difference was found in postoperative morbidity (36.3 vs. 36.7%, p = 0.77). CONCLUSIONS The present study demonstrates that for patients requiring salvage surgery after TEM, TaTME is associated with significantly higher rates of sphincter-sparing surgery when compared to conventional transabdominal TME while producing adequate short-term oncologic outcomes. Salvage surgery after TEM might be a clear indication for TaTME rather than conventional surgery.


title: Comparison Between Neurally Adjusted Ventilatory Assist and Pressure Support Ventilation Levels in Terms of Respiratory Effort.

text: OBJECTIVES To understand the potential equivalence between neurally adjusted ventilatory assist and pressure support ventilation levels in terms of respiratory muscle unloading. To compare the respiratory pattern, variability, synchronization, and neuromuscular coupling within comparable ranges of assistance. DESIGN Prospective single-center physiologic study. SETTING A 13-bed university medical ICU. PATIENTS Eleven patients recovering from respiratory failure. INTERVENTIONS The following levels of assistance were consecutively applied in a random order: neurally adjusted ventilatory assist levels: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, and 7 cm H2O/μvolt; pressure support levels: 7, 10, 15, 20, and 25 cm H2O. MEASUREMENTS AND MAIN RESULTS Flow, airway pressure, esophageal pressures, and peak electrical activity of the diaphragm were continuously recorded. Breathing effort was calculated. To express the percentage of assist assumed by the ventilator, the total pressure including muscular and ventilator pressure was calculated. The median percentage of assist ranged from 33% (24-47%) to 82% (72-90%) between pressure support 7 and 25 cm H2O. Similar levels of unloading were observed for neurally adjusted ventilatory assist levels from 0.5 cm H2O/μvolt (46% [40-51%]) to 2.5 cm H2O/μvolt (80% [74-84%]). Tidal variability was higher during neurally adjusted ventilatory assist and ineffective efforts appeared only in pressure support. In neurally adjusted ventilatory assist, double triggering occurred sometimes when electrical activity of the diaphragm signal depicted a biphasic aspect, and an abnormal oscillatory pattern was frequently observed from 4 cm H2O/μvolt. For both modes, the relationship between peak electrical activity of the diaphragm and muscle pressure depicted a curvilinear profile. CONCLUSIONS In patients recovering from acute respiratory failure, levels of neurally adjusted ventilatory assist between 0.5 and 2.5 cm H2O/μvolt are comparable to pressure support levels ranging from 7 to 25 cm H2O in terms of respiratory muscle unloading. Neurally adjusted ventilatory assist provides better patient-ventilator interactions but can be sometimes excessively sensitive to electrical activity of the diaphragm in terms of triggering.


title: The evaluation of pelvic floor muscle strength in women with pelvic floor dysfunction: A reliability and correlation study.

text: AIMS The purposes of this study were: (i) to evaluate the reliability of vaginal palpation, vaginal manometry, vaginal dynamometry; and surface (transperineal) electromyography (sEMG), when evaluating pelvic floor muscle (PFM) strength and/or activation; and (ii) to determine the associations among PFM strength measured using these assessments. METHODS One hundred and fifty women with pelvic floor disorders participated on one occasion, and 20 women returned for the same investigations by two different raters on 3 different days. At each session, PFM strength was assessed using palpation (both the modified Oxford Grading Scale and the Levator ani testing), manometry, and dynamometry; and PFM activation was assessed using sEMG. RESULTS The interrater reliability of manometry, dynamometry, and sEMG (both root-mean-square [RMS] and integral average) was high (Lin's Concordance Correlation Coefficient [CCC] = 0.95, 0.93, 0.91, 0.86, respectively), whereas the interrater reliability of both palpation grading scales was low (Cohen's Kappa [k] = 0.27-0.38). The intrarater reliability of manometry (CCC = 0.96), and dynamometry (CCC = 0.96) were high, whereas intrarater reliability of both palpation scales (k = 0.78 for both), and of sEMG (CCC = 0.79 vs 0.80 for RMS vs integral average) was moderate. The Bland-Altman plot showed good inter and intrarater agreement, with little random variability for all instruments. The correlations among palpation, manometry, and dynamometry were moderate (coefficient of determination [r2 ] ranged from 0.52 to 0.75), however, transperineal sEMG amplitude was only weakly correlated with all measures of strength (r2 = 0.23-0.30). CONCLUSIONS Manometry and dynamometry are more reliable tools than vaginal palpation for the assessment of PFM strength in women with pelvic floor disorders, especially when different raters are involved. The different PFM strength measures used clinically are moderately correlated; whereas, PFM activation recorded using transperineal sEMG is only weakly correlated with PFM strength. Results from perineal sEMG should not be interpreted in the context of reporting PFM strength.


title: Biosafety and biosecurity in veterinary laboratories.

text: With recent outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV), anthrax, Nipah and the highly pathogenic avian influenza virus, much emphasis has been placed on the rapid identification of infectious agents globally. As a result, laboratories are building capacity, conducting more advanced and sophisticated research, increasing their staff, and establishing reference collections of dangerous pathogens in an attempt to reduce the impact of infectious disease outbreaks and to characterise disease-causing agents. With this expansion, the global laboratory community has started to focus on laboratory biosafety and biosecurity in order to prevent the accidental and/or intentional release of these agents. Laboratory biosafety and biosecurity systems are used around the world to help to mitigate the risks posed by dangerous pathogens in the laboratory. Veterinary laboratories carry unique responsibilities with regard to workers and communities to handle disease-causing microorganisms safely and securely. Many microorganisms studied in veterinary laboratories not only infect animals, but also have the potential to infect humans. This paper will discuss the fundamentals of laboratory biosafety and biosecurity.


title: Inhibiting the deubiquitinating enzymes (DUBs).

text: The diverse roles of deubiquitinating enzymes, or DUBs, in determining the fate of specific proteins continue to unfold. Concurrent with the revelation of DUBs as potential therapeutic targets are publications of small molecule inhibitors of these enzymes. In this review, we summarize these molecules and their associated data and suggest additional experiments to further validate and characterize these compounds. We believe the field of drug discovery against DUBs is still in its infancy, but advances in assay development, biophysical techniques, and screening libraries hold promise for identifying suitable agents that could advance into the clinic.


title: Impact of Political Economy on Population Health: A Systematic Review of Reviews.

text: Background. Although there is a large literature examining the relationship between a wide range of political economy exposures and health outcomes, the extent to which the different aspects of political economy influence health, and through which mechanisms and in what contexts, is only partially understood. The areas in which there are few high-quality studies are also unclear. Objectives. To systematically review the literature describing the impact of political economy on population health. Search Methods. We undertook a systematic review of reviews, searching MEDLINE, Embase, International Bibliography of the Social Sciences, ProQuest Public Health, Sociological Abstracts, Applied Social Sciences Index and Abstracts, EconLit, SocINDEX, Web of Science, and the gray literature via Google Scholar. Selection Criteria. We included studies that were a review of the literature. Relevant exposures were differences or changes in policy, law, or rules; economic conditions; institutions or social structures; or politics, power, or conflict. Relevant outcomes were any overall measure of population health such as self-assessed health, mortality, life expectancy, survival, morbidity, well-being, illness, ill health, and life span. Two authors independently reviewed all citations for relevance. Data Collection and Analysis. We undertook critical appraisal of all included reviews by using modified Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria and then synthesized narratively giving greater weight to the higher-quality reviews. Main Results. From 4912 citations, we included 58 reviews. Both the quality of the reviews and the underlying studies within the reviews were variable. Social democratic welfare states, higher public spending, fair trade policies, extensions to compulsory education provision, microfinance initiatives in low-income countries, health and safety policy, improved access to health care, and high-quality affordable housing have positive impacts on population health. Neoliberal restructuring seems to be associated with increased health inequalities and higher income inequality with lower self-rated health and higher mortality. Authors' Conclusions. Politics, economics, and public policy are important determinants of population health. Countries with social democratic regimes, higher public spending, and lower income inequalities have populations with better health. There are substantial gaps in the synthesized evidence on the relationship between political economy and health, and there is a need for higher-quality reviews and empirical studies in this area. However, there is sufficient evidence in this review, if applied through policy and practice, to have marked beneficial health impacts. Public Health Implications. Policymakers should be aware that social democratic welfare state types, countries that spend more on public services, and countries with lower income inequalities have better self-rated health and lower mortality. Research funders and researchers should be aware that there remain substantial gaps in the available evidence base. One such area concerns the interrelationship between governance, polities, power, macroeconomic policy, public policy, and population health, including how these aspects of political economy generate social class processes and forms of discrimination that have a differential impact across social groups. This includes the influence of patterns of ownership (of land and capital) and tax policies. For some areas, there are many lower-quality reviews, which leave uncertainties in the relationship between political economy and population health, and a high-quality review is needed. There are also areas in which the available reviews have identified primary research gaps such as the impact of changes to housing policy, availability, and tenure.


title: A new regularization method for dynamic load identification.

text: Dynamic forces are very important boundary conditions in practical engineering applications, such as structural strength analysis, health monitoring and fault diagnosis, and vibration isolation. Moreover, there are many applications in which we have found it very difficult to directly obtain the expected dynamic load which acts on a structure. Some traditional indirect inverse analysis techniques are developed for load identification by measured responses. These inverse problems about load identification mentioned above are complex and inherently ill-posed, while regularization methods can deal with this kind of problem. However, most of regularization methods are only limited to solve the pure mathematical numerical examples without application to practical engineering problems, and they should be improved to exclude jamming of noises in engineering. In order to solve these problems, a new regularization method is presented in this article to investigate the minimum of this minimization problem, and applied to reconstructing multi-source dynamic loads on the frame structure of hydrogenerator by its steady-state responses. Numerical simulations of the inverse analysis show that the proposed method is more effective and accurate than the famous Tikhonov regularization method. The proposed regularization method in this article is powerful in solving the dyanmic load identification problems.


title: Reconstruction of DNA sequences using genetic algorithms and cellular automata: towards mutation prediction?

text: Change of DNA sequence that fuels evolution is, to a certain extent, a deterministic process because mutagenesis does not occur in an absolutely random manner. So far, it has not been possible to decipher the rules that govern DNA sequence evolution due to the extreme complexity of the entire process. In our attempt to approach this issue we focus solely on the mechanisms of mutagenesis and deliberately disregard the role of natural selection. Hence, in this analysis, evolution refers to the accumulation of genetic alterations that originate from mutations and are transmitted through generations without being subjected to natural selection. We have developed a software tool that allows modelling of a DNA sequence as a one-dimensional cellular automaton (CA) with four states per cell which correspond to the four DNA bases, i.e. A, C, T and G. The four states are represented by numbers of the quaternary number system. Moreover, we have developed genetic algorithms (GAs) in order to determine the rules of CA evolution that simulate the DNA evolution process. Linear evolution rules were considered and square matrices were used to represent them. If DNA sequences of different evolution steps are available, our approach allows the determination of the underlying evolution rule(s). Conversely, once the evolution rules are deciphered, our tool may reconstruct the DNA sequence in any previous evolution step for which the exact sequence information was unknown. The developed tool may be used to test various parameters that could influence evolution. We describe a paradigm relying on the assumption that mutagenesis is governed by a near-neighbour-dependent mechanism. Based on the satisfactory performance of our system in the deliberately simplified example, we propose that our approach could offer a starting point for future attempts to understand the mechanisms that govern evolution. The developed software is open-source and has a user-friendly graphical input interface.


title: Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial.

text: BACKGROUND Venous thromboembolism is a common, potentially avoidable cause of death and morbidity in patients in hospital, including those with stroke. In surgical patients, intermittent pneumatic compression (IPC) reduces the risk of deep vein thrombosis (DVT), but no reliable evidence exists about its effectiveness in patients who have had a stroke. We assessed the effectiveness of IPC to reduce the risk of DVT in patients who have had a stroke. METHODS The CLOTS 3 trial is a multicentre parallel group randomised trial assessing IPC in immobile patients (ie, who cannot walk to the toilet without the help of another person) with acute stroke. We enrolled patients from day 0 to day 3 of admission and allocated them via a central randomisation system (ratio 1:1) to receive either IPC or no IPC. A technician who was masked to treatment allocation did a compression duplex ultrasound (CDU) of both legs at 7-10 days and, wherever practical, at 25-30 days after enrolment. Caregivers and patients were not masked to treatment assignment. Patients were followed up for 6 months to determine survival and later symptomatic venous thromboembolism. The primary outcome was a DVT in the proximal veins detected on a screening CDU or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomisation. Patients were analysed according to their treatment allocation. TRIAL REGISTRATION ISRCTN93529999. FINDINGS Between Dec 8, 2008, and Sept 6, 2012, 2876 patients were enrolled in 94 centres in the UK. The included patients were broadly representative of immobile stroke patients admitted to hospital and had a median age of 76 years (IQR 67-84). The primary outcome occurred in 122 (8·5%) of 1438 patients allocated IPC and 174 (12·1%) of 1438 patients allocated no IPC; an absolute reduction in risk of 3·6% (95% CI 1·4-5·8). Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU, the adjusted OR for the comparison of 122 of 1267 patients vs 174 of 1245 patients was 0·65 (95% CI 0·51-0·84; p=0·001). Deaths in the treatment period occurred in 156 (11%) patients allocated IPC and 189 (13%) patients allocated no IPC died within the 30 days of treatment period (p=0·057); skin breaks on the legs were reported in 44 (3%) patients allocated IPC and in 20 (1%) patients allocated no IPC (p=0·002); falls with injury were reported in 33 (2%) patients in the IPC group and in 24 (2%) patients in the no-IPC group (p=0·221). INTERPRETATION IPC is an effective method of reducing the risk of DVT and possibly improving survival in a wide variety of patients who are immobile after stroke. FUNDING National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme, UK; Chief Scientist Office of Scottish Government; Covidien (MA, USA).


title: Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections.

text: Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses.