bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation
Authors: Fornia Luca , Rossi Marco , Rabuffetti Marco , Leonetti Antonella , Puglisi Guglielmo , Viganò Luca , Simone Luciano , Howells Henrietta , Bellacicca Andrea , Bello Lorenzo , Cerri Gabriella
Published: June 2019

Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.
DOZ047.45: The effect of transanastomotic feeding tubes on anastomotic strictures following esophageal atresia repair
Authors: LaRusso K , Lakabi R , Lévesque D , Laberge J-M , Emil S
Published: June 2019

Purpose

Recent studies have identified the use of transanastomotic tubes (TATs) as an independent risk factor for the development of strictures after repair of esophageal atresia (EA). We retrospectively analyzed a 25-year cohort of EA patients (1993–2018) to investigate the effect of TAT use on stricture formation.

Methods

Following institutional approval (MP-37–2019-2991), a retrospective study of all Type C and Type D EA patients who underwent primary repair was examined. Infants were included if they had surgery within the first two weeks of life and had a least one year of follow-up. Stricture was defined as the presence of symptoms confirmed by imaging and/or endoscopy. A multiple logistic regression model was used to compare stricture in those with and without TATs. Poisson regression was used to evaluate differences in postoperative outcomes listed in Table 1.

Results

Strictures occurred in 35 of 85 patients (41%). Of those with strictures, 25 (71%) had transanastomotic tubes. There was no significant difference in stricture rates between those with TATs and without TATs (odd ratio (OR) = 1.94, 95% confidence interval (CI): 0.78–5.06, P = 0.161). However, those who had TATs had a significantly higher number of dilations overall (rate ratio (RR) = 1.47, 95% CI: 1.09–2.03, P = 0.014). In patients with TATs, the time to enteral feeding was significantly shorter (RR = 0.37, 95% CI: 0.28–0.49, P < 0.001), but the time to oral feeding was significantly longer (RR = 1.37, CI: 1.20–1.56, P < 0.001). The TAT group had a 34% lower mean hospital length of stay. On multivariate analysis, there remained no difference in stricture rates between the two groups.

Conclusion

Transanastomotic tubes do not seem to result in increased strictures rates in our cohort, but significantly decrease time to initiation of enteral feeds and reduce the duration of hospital stay.
DOZ047.60: Evaluation of gastroesophageal reflux in children born with esophageal atresia using pH and impedance monitoring
Authors: Vergouwe F W T , van Wijk M P , ten Kate C A , Spaander M C W , Bruno M J , Wijnen R M H , Schnater J M , IJsselstijn H
Published: June 2019

Aim of the Study

The ESPHGAN-NASPGHAN guideline (Krishnan, 2016) recommends routine prescription of proton pump inhibitors in the first year of life after esophageal atresia (EA) repair, and to monitor gastroesophageal reflux (GER) using pH-impedance (pH-MII) monitoring and/or endoscopy at time of discontinuation and during long term follow up of these patients. This study aimed to evaluate acid and non-acid GER in infants and school-aged children with EA using pH-MII monitoring.

Methods

Children born with EA between 2011–2017, who underwent a 24-hour pH-MII study during infancy (≤18 months) or at 8 years old as part of a standardized longitudinal follow-up program, were included. Exclusion criteria were: isolated tracheoesophageal fistula, esophageal replacement therapy, tube feeding and monitoring < 18 hours. Anti-acid therapy was discontinued before pH-MII measurement. Data was collected on reflux index (RI; exposure to pH < 4 in %, >7% considered abnormal), retrograde bolus movements (RBM) and bolus clearance time (BCT). Automatically detected RBM were manually reviewed and modified/deleted if necessary.

Results

We included 57 children (51% male, 2% isolated EA, 44% thoracoscopic repair): 24 infants (median age 0.6 years) and 33 school-aged children (median age 8.2 years). In infants, median RI was 2.6% (abnormal in n = 2), median RBM was 61 (62% non-acid, 58% mixed) and median of the mean BCT was 11 seconds. In school-aged children, median RI was 0.3% (abnormal in n = 4), median RBM was 21 (64% non-acid, 75% mixed) and median of the mean BCT was 13 seconds. Of the automatically detected 3,313 RBM, 1,292 were manually deleted from the tracings: 52% of non-acid RBM and 8% of acid RBM (mainly misinterpreted swallows or one event recognized as several events).

Conclusions

Most children with EA off medication have a normal RI, yet experience a significant number of non-acid RBM. After manual revision of the tracings a high percentage of RBM was deleted. Our data show that automated impedance analysis software needs refinement for use in infants and children with EA, and question the need for standard anti-acid therapy in these patients.
DOZ047.63: Closing the gap: transitioning adolescents with esophageal atresia to adult care
Authors: Hawley A D , Brooks J-A E , Nightingale M G , Teague W J , Crameri J , Culnane E
Published: June 2019

Introduction

Evidence supports engaging adolescents and carers in an individualized transition process to improve health outcomes through increased patient knowledge, skills, adherence, quality of life and ultimately, engagement with adult services. Further, a comprehensive transition process promotes confidence in navigating adult health services. While transition for chronic medical cohorts has received considerable attention over decades, there is increasing recognition of the importance of transition for adolescents with surgical conditions.

Background

It is widely held that the transition of adolescents born with esophageal atresia (OA) from pediatric to adult services is important, and if not managed well, may compromise outcomes. We designed and implemented a transition process for adolescent OA patients at our hospital (with establishment of a transfer pathway in partnership with adult health services) in 2017.

Methods

Following implementation of a transition process a retrospective review was undertaken in 2019 to identify themes from the dedicated Transition Support Service (TSS) Clinics (October, 2017–December, 2018) for OA patients aged 15–19 years. Patients were identified from an institutional database (Nate Myers Oesophageal Atresia Database, Royal Children's Hospital, Melbourne).

These patients had previously been invited to: Attend TSS Clinics as part of routine clinical care.Re-engage in multidisciplinary follow-up (if necessary) including with a consultant surgeon, OA nurse and respiratory physician.

Institutional ethics approval was obtained prior to commencement of the study (HREC #QA/51265/RCHM-2019).

Results

A total of 18 adolescent OA patients and their parents attended RCH TSS and associated follow-up clinics. We observed three key themes in attendees reports and experiences: Poor health knowledge: 56% of adolescents had poor knowledge about their OA, including previous surgery, possible complications and their symptoms;Poor compliance: 54% of adolescents reported poor compliance with prescribed regular medications (e.g. anti-reflux therapy);Mental health issues: 39% of adolescents identified as having mental health concerns, e.g. low mood or clinical depression, anxiety, anger or had engaged in self-harm. Anxiety about transfer to adult services was moderate to high in the majority (61%) of adolescents and their parents.

Conclusions

The themes identified in this study support the need for, and importance of, a structured process to transition adolescents born with OA to adult services.
DOZ047.68: Intralesional steroid injection therapy for the treatment of esophageal anastomotic stricture in a pediatric esophageal atresia population
Authors: Ngo P D , Kamran A , Clark S J , Jennings R W , Hamilton T E , Smithers C J , Zendejas B , Yasuda J L , Zurakowski D , Manfredi M A
Published: June 2019

Background and Aims

The role of intralesional steroid injection (ISI) in the treatment of anastomotic stricture in esophageal atresia (EA) patients remains unclear. The aim of this study is to evaluate the efficacy and safety of ISI in a large pediatric EA population.

Methods

One-hundred fifty eight EA patients who had undergone at least one ISI for the treatment of esophageal anastomotic stricture between 2010 and 2017 were identified. The change in stricture diameter (ΔD) was compared between procedures with balloon dilation alone (ISI-) and balloon dilation with steroid injection (ISI+). Assessment for change in efficacy with increasing numbers of ISI interventions was performed.

Results

A total of 1055 balloon dilations were performed (452 ISI+). The median ΔD was significantly greater in the group of steroid injection procedures: 1 mm (IQR 0, 3) versus 0 mm (IQR -1, 1.5) (P < 0.0001). The ISI+ group had greater percentage of improved stricture diameter (P < 0.0001) and lesser percentages of unchanged and decreased stricture diameters at subsequent endoscopy (P = 0.0009, P = 0.003). The ΔD for each of an anastomosis’ first 3 ISI+ procedures was greater than the ΔD for its subsequent ISI+ procedures: 1 mm (IQR 0, 3) versus 0.5 mm (IQR -1.25, 2) (P = 0.001). Multivariable logistic regression confirmed the significance of ISI on increasing the likelihood of improved stricture diameter.

Conclusions

This study demonstrates that intralesional steroid injection with dilation was well tolerated and improved anastomotic stricture diameter more than dilation alone. The benefit of ISI over dilation alone was limited to the first three ISI procedures.
DOZ047.83: Coordination of care through implementation of a multidisciplinary clinic for patients with esophageal atresia and tracheoesophageal fistula
Authors: Platt J , Mitchell I , Bjornson C , Bailey J A M
Published: June 2019

Introduction

Esophageal atresia/tracheoesophageal atresia (EA/TEF) is a multisystem congenital anomaly. Initial treatment is complex and ongoing complications are numerous. Coordination of care has been shown to reduce costs and hospitalizations in complex populations. A previous study at our center demonstrated that children with EA/TEF lacked coordinated care. A multidisciplinary clinic was established to provide coordinated care, screen for complications, provide anticipatory guidance, and improve outpatient access.

Methods

This single-center retrospective cohort study included children with EA/TEF born between March 2005 and March 2011 and enrolled in the clinic. Patients with EA alone were excluded. A chart review was completed to identify demographics, hospitalizations, emergency visits, clinic visits, coordination of outpatient care, and adherence to the intended clinic schedule.

Results

Twenty-five patients were included; 84% had a C-type EA/TEF. Multidisciplinary clinics had an average of 4.3 health care providers (1.75 physicians) per visit. Adherence to the visit schedule was 91.4%. The average length of stay (46.2 + 37.9 days) for the initial hospital admission was similar to the previous study cohort. Subsequent hospital admissions were reduced in number and length of stay, most notably in the first two years of life (0–1 year: 1.28 + 1.2 admissions/patient; 10.7 + 19.1 days/admission; 1–2 years: 0.6 + 0.76 admissions/patient; 3.7 + 3.2 days/admission).

Conclusions

Multidisciplinary care clinics for medically complex children such as those with EA/TEF can improve care through coordination of visits with multiple health care providers and may contribute to reduced use of acute care services.
DOZ047.98: The role of laryngeal electromyography in differential diagnosis of vocal cord immobility: a case report
Authors: Salvati A , Trozzi M , Meucci D , Tropiano M L , Bottero S
Published: June 2019

Object

The term ‘vocal cord immobility’ (VCI) encompasses both vocal cord paralysis and crico-arytenoid joint ankylosis (CAJA). Bilateral VCI represents an emergency condition characterized by stridor and respiratory distress sometimes requiring tracheostomy to ensure an adequate and safe airway. The aim of this study is to describe the diagnostic and therapeutic management of a rare case of congenital bilateral CAJA in a patient without pregnancy complications, perinatal traumas, or other comorbidities.

Materials and Methods

The patient was born full term by C-section after a healthy pregnancy (BW 3270 g, APGAR 9 at 5'). After birth she presented severe stridor with respiratory distress. She was admitted to our hospital when she was 3 months old. The diagnostic assessment was performed with airway endoscopy, pulmonary function tests (PFT), sleep study, echocardiogram, neurological evaluation, chest computed tomography (CT) scan, and brain magnetic resonance imaging (MRI). Laryngeal electromyography (LEMG) with endoscopic placement of Hookwire electrodes was carried out for the differential diagnosis between paralysis and ankylosis and the subsequent choice of the treatment. PFT and sleep study were repeated after each endoscopic procedure.

Results

The first airway endoscopy showed bilateral VCI in paramedian position and palpatory evidence of bilateral crico-arytenoid joint fixation. PFT highlighted inspiratory obstruction at the flow/volume and flow/time curves and tidal volume reduction. Sleep study was indicative of mild–moderate obstructive apnea. Echocardiogram, neurological evaluation, brain MRI, and chest CT scan did not detect anomalies. LEMG showed continuous low-amplitude basal activity in all analyzed muscles, in the absence of spontaneous neurotonic activations. Motor evoked potentials (MEP) denoted normal left response and minimum right delay. Two glottic dilations were performed with 7 and 8 mm balloons determining the decrease of stridor and good respiratory balance confirmed by PFT. Endoscopy showed a slight recovery of laryngeal motility.

Conclusion

The management of this rare clinical case points out the crucial role of a careful and complete endoscopic examination including the palpation of the crico-arytenoid joints. Moreover LEMG represents an important instrument for the correct differential diagnosis in VCI. In the future the use of LEMG could be mandatory in pediatric patients in order to avoid tracheotomy in favor of more conservative procedures.
Imaging residual inflammatory cardiovascular risk
Authors: Antoniades Charalambos , Antonopoulos Alexios S , Deanfield John
Published: June 2019

Targeting residual cardiovascular risk in primary and secondary prevention, would allow deployment of novel therapeutic agents, facilitating precision medicine. For example, lowering vascular inflammation is a promising strategy to reduce the residual inflammatory cardiovascular risk in patients already receiving optimal medical therapy, but prescribing novel anti-inflammatory treatments will be problematic due to the lack of specific companion diagnostic tests, to guide their targeted use in clinical practice. Currently available tests for the detection of coronary inflammation are either non-specific for the cardiovascular system (e.g. plasma biomarkers) or expensive and not readily available (e.g. hybrid positron emission tomography imaging). Recent technological advancements in coronary computed tomography angiography (CCTA) allow non-invasive detection of high-risk plaque features (positive remodelling, spotty calcification, low attenuation plaque, and napkin-ring sign) and help identify the vulnerable patient, but they provide only indirectly information about coronary inflammation. Perivascular fat attenuation index (FAI), a novel method for assessing coronary inflammation by analysing routine CCTA, captures changes in the perivascular adipose tissue composition driven by inflammatory signals coming from the inflamed coronary artery, by analysing the three-dimensional gradients of perivascular attenuation, followed by adjustments for technical, anatomical, and biological factors. By detecting vascular inflammation, perivascular FAI enhances cardiovascular risk discrimination which could aid more cost-effective deployment of novel therapeutic agents. In this article, we present the existing non-invasive modalities for the detection of coronary inflammation and provide a practical guide for their use in clinical practice.
Transgenerational Obesity and Healthy Aging in Drosophila
Authors: Camilleri-Carter Tara-Lyn , Dowling Damian K , L. Robker Rebecca , Piper Matthew D W
Published: June 2019

Substantial evidence suggests that individuals born to overweight and obese parents suffer detrimental health consequences that dramatically decrease healthy aging. The number of obese individuals worldwide now exceeds the number of under- and malnourished individuals. This obesity epidemic is responsible for approximately 4 million deaths worldwide each year, and predisposes sufferers to a range of age-related diseases such as cardiovascular diseases, and metabolic syndrome. Additionally, obesity is associated with an accelerated onset of age-related ailments, such as cancers and inflammation. The importance of dietary interventions to reduce the incidence of obesity is magnified by emerging evidence that parental physiology can predispose future generations to poor health outcomes. Characterizing and understanding these effects, and how they are mediated, is important if we are to continue to drive improvements to population health. In this article, we synthesize evidence for the intergenerational and transgenerational phenotypic effects of parental obesity. We concentrate on how the fruit fly Drosophila melanogaster can be used as a model to study these effects. Fruit flies are highly tractable, and their conserved nutrient signaling and metabolic pathways make them an ideal model for studying nutritional effects on metabolic, reproductive, and aging phenotypes.
Pyridox (am) ine 5'-phosphate oxidase deficiency induces seizures in Drosophila melanogaster
Authors: Chi Wanhao , Iyengar Atulya S R , Albersen Monique , Bosma Marjolein , Verhoeven-Duif Nanda M , Wu Chun-Fang , Zhuang Xiaoxi
Published: June 2019

Pyridox (am) ine 5'-phosphate oxidase (PNPO) is a rate-limiting enzyme in converting dietary vitamin B6 (VB6) to pyridoxal 5'-phosphate (PLP), the biologically active form of VB6 and involved in the synthesis of neurotransmitters including γ-aminobutyric acid (GABA), dopamine, and serotonin. In humans, PNPO mutations have been increasingly identified in neonatal epileptic encephalopathy and more recently also in early-onset epilepsy. Till now, little is known about the neurobiological mechanisms underlying PNPO-deficiency-induced seizures due to the lack of animal models. Previously, we identified a c.95 C>A missense mutation in sugarlethal (sgll)—the Drosophila homolog of human PNPO (hPNPO)—and found mutant (sgll95) flies exhibiting a lethal phenotype on a diet devoid of VB6. Here, we report the establishment of both sgll95 and ubiquitous sgll knockdown (KD) flies as valid animal models of PNPO-deficiency-induced epilepsy. Both sgll95 and sgll KD flies exhibit spontaneous seizures before they die. Electrophysiological recordings reveal that seizures caused by PNPO deficiency have characteristics similar to that in flies treated with the GABA antagonist picrotoxin. Both seizures and lethality are associated with low PLP levels and can be rescued by ubiquitous expression of wild-type sgll or hPNPO, suggesting the functional conservation of the PNPO enzyme between humans and flies. Results from cell type-specific sgll KD further demonstrate that PNPO in the brain is necessary for seizure prevention and survival. Our establishment of the first animal model of PNPO deficiency will lead to better understanding of VB6 biology, the PNPO gene and its mutations discovered in patients, and can be a cost-effective system to test therapeutic strategies.
Toward a Global Genomic Epidemiology of Meningococcal Disease
Authors: Retchless Adam C , Fox LeAnne M , Maiden Martin C J , Smith Vincent , Harrison Lee H , Glennie Linda , Harrison Odile B , Wang Xin
Published: June 2019

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.
Immunoglobulin-Like Transcript 5 Inhibits Macrophage-Mediated Bacterial Killing and Antigen Presentation During Sepsis
Authors: Ming Siqi , Li Musheng , Wu Minhao , Zhang Jianhui , Zhong Haibo , Chen Junyang , Huang Yaopan , Bai Jun , Huang Li , Chen Juan , Lin Quanshi , Liu Jiao , Tao Jianping , He Duanman , Huang Xi
Published: June 2019

Background

Immunosuppression contributes to the mortality of sepsis. However, the underlying mechanism remains unclear.

Methods

In the present study, we investigated the role of inhibitory receptor immunoglobulin-like transcript 5 (ILT5) in sepsis. We first screened the expression of ILT family members, and we found that ILT5 was dramatically up-regulated in the peripheral blood mononuclear cells from sepsis patients versus healthy donors.

Results

Knockdown of ILT5 by small interfering ribonucleic acid increased bacterial killing and reactive oxygen species production in THP-1 and RAW264.7 cells. Moreover, ILT5-expressing monocytes/macrophages exhibited lower expression of antigen-presenting molecules including major histocompatibility complex-II and CD80. In the in vitro coculture system with monocytes/macrophages, blockage of ILT5 facilitated Th1 proliferation and differentiation of CD4+ T cells. Furthermore, in vivo experiments demonstrated that pretreatment with ILT5 blocking peptide improved the survival and pulmonary pathology of septic mice.

Conclusions

Together, our study identified ILT5 as an immunosuppressive regulator during sepsis, which may provide potential therapeutic strategy for sepsis.
Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction
Authors: Lartey Sarah , Zhou Fan , Brokstad Karl A , Mohn Kristin G-I , Slettevoll Steffen A , Pathirana Rishi D , Cox Rebecca J
Published: June 2019

Background

Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown.

Methods

We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay.

Results

We report that LAIV induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV.

Conclusions

Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.
Algorithms at War: The Promise, Peril, and Limits of Artificial Intelligence
Authors: Jensen Benjamin M , Whyte Christopher , Cuomo Scott
Published: June 2019

How might rapid advances in artificial intelligence (AI) technologies affect the construction and application of military power? Despite the emerging importance of AI systems in defense modernization initiatives, there has been little empirical or theoretical study from the perspective of the international relations (IR) and security studies fields. This article addresses this shortcoming by describing AI developments and assessing the manner in which AI is likely to affect military organizations. We focus specifically on military power, as new methods and modes thereof will alter the constitution of security relationships around the world and affect the ability of states to bargain, signal, and influence in the twenty-first century. We argue that, though rapid adoption of AI technologies stands to transform states’ ways of war on a number of fronts, an AI revolution brings with it new forms of risk that must be reconciled with the widespread integration of algorithmic systems across military functions. Where new technology promises a transformation of the character of military power in some veins, it also complicates the cognitive aspects of decision-making and bureaucratic interactions in security institutions. The speed with which complex integrated AI systems enable entirely new modes of war also stands to detach human agency in a potentially destabilizing fashion from the conduct of warfare on several fronts. Preventing the negative externalities of these “ghosts in the machine” will involve significant efforts to educate decision makers, promote accountability, and restrain irresponsible employment of AI.
Dramatic rise in the proportion of ESBL-producing Escherichia coli and Klebsiella pneumoniae among clinical isolates identified in Canadian hospital laboratories from 2007 to 2016
Authors: Denisuik Andrew J , Karlowsky James A , Adam Heather J , Baxter Melanie R , Lagacé-Wiens Philippe R S , Mulvey Michael R , Hoban Daryl J , Zhanel George G ,   Canadian Antimicrobial Resistance Alliance (CARA) and CANWARD, Zhanel George G , Hoban Daryl J , Adam Heather J , Baxter Melanie R , Nichol Kimberly A , Lagacé-Wiens Philippe R S , Walkty Andrew , Karlowsky James A , Blondeau J , Slinger R , Davidson R , Zhanel G , Hoban D , Delport J , Ellis C , Laverdière M , Loo V , Poutanen S , Fuller J , Roscoe D , Desjardins M , Matukas L , Goyette M , Lee C , Carignan A , Bergevin M , Pelletier R
Published: June 2019

Objectives

To assess the prevalence, antimicrobial susceptibilities and molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae infecting patients receiving care in Canadian hospitals from January 2007 to December 2016.

Methods

Clinical isolates of E. coli (n = 8387) and K. pneumoniae (n = 2623) submitted to CANWARD, an ongoing Canadian national surveillance study, were tested using the CLSI reference broth microdilution method to determine their susceptibility to 15 antimicrobial agents. ESBL-producing E. coli and K. pneumoniae confirmed by the CLSI phenotypic method and putative AmpC-producing E. coli underwent PCR testing and DNA sequencing to identify resistance genes. Annual proportions of isolates harbouring ESBL and AmpC genes were assessed by the Cochran–Armitage test of trend.

Results

The annual proportion of isolates of E. coli that were ESBL producing increased from 3.4% in 2007 to 11.1% in 2016 (P < 0.0001); >95% of ESBL-producing E. coli were susceptible to amikacin, colistin, ertapenem, meropenem and tigecycline. The proportion of isolates of K. pneumoniae that were ESBL producing increased from 1.3% in 2007 to 9.7% in 2016 (P < 0.0001); >95% of ESBL-producing K. pneumoniae were susceptible to amikacin and meropenem. CTX-M-15 was the predominant genotype in both ESBL-producing E. coli (64.2% of isolates) and ESBL-producing K. pneumoniae (51.0%). The annual proportion of isolates of E. coli that were AmpC producing [annual proportion mean 1.9% (range 0.3%–3.1%)] was unchanged from 2007 to 2016 (P > 0.5).

Conclusions

The prevalence of both ESBL-producing E. coli and K. pneumoniae increased significantly in Canada during the study period while the prevalence of AmpC-producing E. coli remained low and stable.
An investigation of the effects of procalcitonin testing on antimicrobial prescribing in respiratory tract infections in an Irish university hospital setting: a feasibility study
Authors: O’Riordan F , Shiely F , Byrne S , O’Brien D , Palmer B , Dahly D , O’Connor T M , Curran D , Fleming A
Published: June 2019

Background

Diagnostic uncertainty and a high prevalence of viral infections present unique challenges for antimicrobial prescribing for respiratory tract infections (RTIs). Procalcitonin (PCT) has been shown to support prescribing decisions and reduce antimicrobial use safely in patients with RTIs, but recent study results have been variable.

Methods

We conducted a feasibility study of the introduction of PCT testing in patients admitted to hospital with a lower RTI to determine if PCT testing is an effective and worthwhile intervention to introduce to support the existing antimicrobial stewardship (AMS) programme and safely decrease antimicrobial prescribing in patients admitted with RTIs.

Results

A total of 79 patients were randomized to the intervention PCT-guided treatment group and 40 patients to the standard care respiratory control group. The addition of PCT testing led to a significant decrease in duration of antimicrobial prescriptions (mean 6.8 versus 8.9 days, P = 0.012) and decreased length of hospital stay (median 7 versus 8 days, P = 0.009) between the PCT and respiratory control group. PCT did not demonstrate a significant reduction in antimicrobial consumption when measured as DDDs and days of therapy.

Conclusions

PCT testing had a positive effect on antimicrobial prescribing during this feasibility study. The successful implementation of PCT testing in a randomized controlled trial requires an ongoing comprehensive education programme, greater integration into the AMS programme and delivery of PCT results in a timely manner. This feasibility study has shown that a larger randomized controlled trial would be beneficial to further explore the positive aspects of these findings.
Signal amplification in flow cytometry for cell surface antigen analysis
Authors: Mori Takeshi , Katayama Yoshiki
Published: June 2019

Signal enhancing systems have been introduced to enable detection of cell surface antigens by flow cytometry. Cell surface antigens are important targets that describe the function and lineage of cells. Although flow cytometry is an effective tool for analysing cell surface antigens, this technique has poor sensitivity, which prohibits the detection of many important antigens on cell membranes. Thus, signal amplification is essential for developing practical tools for evaluating cell surface antigens by flow cytometry. Using a bright fluorophore or fluorescent polymer incorporated into antibodies is a straightforward strategy to improve flow cytometry sensitivity but may affect the functional characteristics of the labelled antibody. In contrast, enzymatic signal amplification is a more practical and efficient strategy to improve sensitivity that should not affect antibody activity. Although enzymatic signal amplification still has a number of drawbacks, this approach is a promising strategy to analyse cell surface antigens.
Abundance matching with the mean star formation rate: there is no missing satellites problem in the Milky Way above M200 ∼ 109 M⊙
Authors: Read J I , Erkal D
Published: June 2019

We introduce a novel abundance matching technique that produces a more accurate estimate of the pre-infall halo mass, M200, for satellite galaxies. To achieve this, we abundance match with the mean star formation rate, averaged over the time when a galaxy was forming stars, 〈SFR〉, instead of the stellar mass, M∗. Using data from the Sloan Digital Sky Survey, the GAMA survey and the Bolshoi simulation, we obtain a statistical 〈SFR〉−M200 relation in Λ cold dark matter. We then compare the pre-infall halo mass, $M^{\rm abund}_{200}$, derived from this relation with the pre-infall dynamical mass, $M^{\rm dyn}_{200}$, for 21 nearby dSph and dIrr galaxies, finding a good agreement between the two. As a first application, we use our new 〈SFR〉−M200 relation to empirically measure the cumulative mass function of a volume-complete sample of bright Milky Way satellites within 280 kpc of the Galactic centre. Comparing this with a suite of cosmological ‘zoom’ simulations of Milky Way-mass haloes that account for subhalo depletion by the Milky Way disc, we find no missing satellites problem above M200 ∼ 109 M⊙ in the Milky Way. We discuss how this empirical method can be applied to a larger sample of nearby spiral galaxies.
Broad-band spectral study of X-ray transient MAXI J1820+070 using Swift/XRT and NuSTAR
Authors: Bharali Priya , Chauhan Jaiverdhan , Boruah Kalyanee
Published: June 2019

We report on a NuSTAR and Swift/XRT observation of the newly discovered X-ray transient MAXI J1820+070. Swift/XRT and NuSTAR have concurrently observed the newly detected source on 2018 March 14. We have simultaneously fitted the broad-band spectra obtained from Swift/XRT and NuSTAR. The observed joint spectra in the energy range 0.6–78.0 keV are well modeled with a weak disc black-body emission, dominant thermal Comptonization, and relativistic reflection fraction. We have detected a fluorescent Iron-Kα line relativistically broadened and a Compton hump at ∼30 keV. We constrain the inner disc radius as well as the disc inclination angle, and their values are found to be 4.1$^{+0.8}_{-0.6}$RISCO (where RISCO ≡ radius of the innermost stable circular orbit) or 5.1$^{+1.0}_{-0.7}$ rg (where rg ≡ gravitational radius) and 29.8$^{+3.0}_{-2.7}$°, respectively. The best-fitting broad-band spectra suggest that the source was in the hard state and evolving. The source emission is best described by weak thermal emission along with strong thermal Comptonization from a relatively cold, optically thick, geometrically thin and ionized accretion disc. X-ray spectral modeling helps us to understand the accretion and ejection properties in the vicinity of the compact object.
Dispersion of sausage waves in coronal waveguides with transverse density structuring
Authors: Lopin I , Nagorny I
Published: June 2019

We study dispersion properties of fast-sausage waves in a radially structured coronal magnetic tube with continuous radial density distribution. The models, containing either a non-uniform core or inhomogeneous external medium are considered. The dispersion relations are obtained for a power law density distribution in the corresponding non-uniform region, where the power-law index controls the steepness of the tube boundary. The governing wave equations with varying coefficients were solved with the Wentzel–Kramers–Brillouin (WKB) approximation. The model with the non-uniform core supports the existence of trapped and leaky sausage modes. The density non-uniformity in the core modifies the values of cut-off wave numbers kc. The smaller values of cut-offs, normalized to the effective tube radius r0, correspond to the smaller power index p. The wave dispersion (i.e. dVph/dk) decreases for smaller p. This occurs in the range of not too small longitudinal wave numbers k > kc. For the model, containing inhomogeneous environment the basic dispersion properties are generally identical to that for the monolithic tube model, studied in Lopin & Nagorny (2015b). The waves are trapped for all wave numbers, if the power-law index 0 < n < 2. There are both trapped and leaky regimes for n ≥ 2. The wave dispersion decreases for smaller n, in the range of the intermediate values of the longitudinal wave numbers k > kc. The seismological application of the obtained results is discussed.
The Milky Way Project second data release: bubbles and bow shocks
Authors: Jayasinghe Tharindu , Dixon Don , Povich Matthew S , Binder Breanna , Velasco Jose , Lepore Denise M , Xu Duo , Offner Stella , Kobulnicky Henry A , Anderson Loren D , Kendrew Sarah , Simpson Robert J
Published: June 2019

Citizen science has helped astronomers comb through large data sets to identify patterns and objects that are not easily found through automated processes. The Milky Way Project (MWP), a citizen science initiative on the Zooniverse platform, presents internet users with infrared (IR) images from Spitzer Space Telescope Galactic plane surveys. MWP volunteers make classification drawings on the images to identify targeted classes of astronomical objects. We present the MWP second data release (DR2) and an updated data reduction pipeline written in python. We aggregate ∼3 million classifications made by MWP volunteers during the years 2012–2017 to produce the DR2 catalogue, which contains 2600 IR bubbles and 599 candidate bow shock driving stars. The reliability of bubble identifications, as assessed by comparison to visual identifications by trained experts and scoring by a machine-learning algorithm, is found to be a significant improvement over DR1. We assess the reliability of IR bow shocks via comparison to expert identifications and the colours of candidate bow shock driving stars in the 2MASS point-source catalogue. We hence identify highly reliable subsets of 1394 DR2 bubbles and 453 bow shock driving stars. Uncertainties on object coordinates and bubble size/shape parameters are included in the DR2 catalogue. Compared with DR1, the DR2 bubbles catalogue provides more accurate shapes and sizes. The DR2 catalogue identifies 311 new bow shock driving star candidates, including three associated with the giant H ii regions NGC 3603 and RCW 49.
Evolution of galactic planes of satellites in the eagle simulation
Authors: Shao Shi , Cautun Marius , Frenk Carlos S
Published: June 2019

We study the formation of planes of dwarf galaxies around Milky Way (MW)-mass haloes in the eagle galaxy formation simulation. We focus on satellite systems similar to the one in the MW: spatially thin or with a large fraction of members orbiting in the same plane. To characterize the latter, we introduce a robust method to identify the subsets of satellites that have the most coplanar orbits. Out of the 11 MW classical dwarf satellites, 8 have highly clustered orbital planes whose poles are contained within a 22° opening angle centred around (l, b) = (182°, −2°). This configuration stands out when compared to both isotropic and typical ΛCDM satellite distributions. Purely flattened satellite systems are short-lived chance associations and persist for less than $1\, \rm {Gyr}$. In contrast, satellite subsets that share roughly the same orbital plane are longer lived, with half of the MW-like systems being at least $4\, \rm {Gyr}$ old. On average, satellite systems were flatter in the past, with a minimum in their minor-to-major axes ratio about $9\, \rm {Gyr}$ ago, which is the typical infall time of the classical satellites. MW-like satellite distributions have on average always been flatter than the overall population of satellites in MW-mass haloes and, in particular, they correspond to systems with a high degree of anisotropic accretion of satellites. We also show that torques induced by the aspherical mass distribution of the host halo channel some satellite orbits into the host’s equatorial plane, enhancing the fraction of satellites with coplanar orbits. In fact, the orbital poles of coplanar satellites are tightly aligned with the minor axis of the host halo.
How much does others’ protection matter? Employment protection, future labour market prospects and well-being
Authors: Luecke Christine , Knabe Andreas
Published: June 2019

Employment protection legislation (EPL) is an important determinant of workers’ perceived labour market prospects and also their subjective well-being. Recent studies indicate that it is not only a worker’s own level of protection that matters for individual prospects and well-being, but also that of others. We examine how such cross-effects on well-being are mediated by workers’ perceived risk of job loss and future employability. We apply a structural model to data from the European Quality of Life Survey and the OECD Employment Protection Database. Our results indicate that both permanent and fixed-term workers’ perceived employability is affected by EPL, positively for fixed-term workers and negatively for permanent workers. Stricter protection for permanent workers is positively related to fixed-term workers’ perceived risk of job loss. EPL has significant indirect (cross-)effects on life satisfaction via the mediators. There are no indications for direct, non-mediated effects.
Acute Experimental Pain Responses in Methadone- and Buprenorphine/Naloxone-Maintained Patients Administered Additional Opioid or Gabapentin: A Double-Blind Crossover Pilot Study
Authors: Murnion Bridin Patricia , Rivas Consuelo , Demirkol Apo , Hayes Vicky , Lintzeris Nicholas , Nielsen Suzanne
Published: June 2019

Objective

The study objective was to identify the analgesic efficacy of three different pharmacological strategies in patients receiving methadone or buprenorphine as opioid agonist treatment (OAT). The three pharmacological approaches, a) increasing maintenance methadone/buprenorphine dose by 30%, b) adding oxycodone, or c) adding a single dose of gabapentin, were compared with a control condition of the participant’s usual OAT dose.

Design

A randomized, controlled, double-blinded, double-dummy, within-subject crossover study.

Subjects

Nine participants on stable doses of methadone and eight participants on stable doses of buprenorphine were recruited.

Setting

An outpatient opioid treatment clinic in inner city Sydney, Australia.

Methods

The cold pressor tolerance test was used to examine experimental pain threshold and tolerance. Ratings of subjective drug effects and safety measures (physiological and cognitive) were assessed.

Results

There was no difference in the primary outcome measures of pain thresholds or tolerance between the conditions examined. Interindividual variability was evident. Differences in some subjective measures were identified, including lower pain recall, lower “bad effects,” and higher global satisfaction in the additional methadone condition. In the buprenorphine arm, increased drug liking and “bad effects” were detected with oxycodone administration, while increased subjective intoxication was identified with gabapentin.

Conclusions

There was no evidence of an objective improvement in analgesia with any condition compared with control. Further research is required to optimize pain management strategies in this population.
Adjuvant treatment for endometrial cancer
Authors: Emons Günter , Vordermark Dirk
Published: June 2019

Purpose of review

This article reviews and interprets studies on adjuvant treatment of endometrial cancer published during the last 18 months.

Recent findings

For patients with intermediate and high intermediate risk endometrial cancer, vaginal brachytherapy remains the adjuvant therapy of choice. New molecular markers might help to define patients in this group for whom observation only is sufficient and women who might have benefitted from external beam radiotherapy. Preliminary results from large randomized controlled trials have shown that in early stage, high-risk endometrial cancer the addition of chemotherapy to external beam radiotherapy (EBRT) did not improve survival. The combination of vaginal brachytherapy with three courses of chemotherapy resulted in similar progression-free and overall survival (3 years) as EBRT. In stage III high-risk endometrial cancer, the addition of chemotherapy to EBRT improved failure-free survival but not overall survival (immature data). Chemotherapy alone had the same efficacy concerning progression-free and overall survival (immature data).

Three large randomized clinical trials on the role of adjuvant radio and/or chemotherapy have so far provided only immature results. Discussions about changes of clinical practice should be postponed until mature data from all three trials are available. The impact of new molecular markers for risk stratification will be assessed in ongoing RCTs.
Burnout in OB/GYN Students and Residents
Authors: RIGBY FIDELMA B. , BYNUM BLYTHE , SANTEN SALLY A. , ANABAZHAGAN ARUNA , KARJANE NICOLE
Published: June 2019

In this article we address the concept of burnout, first in the medical student setting, and then in the residency setting. We will review the prevalence followed by a discussion of risk factors, consequences, and finally thoughts on prevention and intervention.
Beam emittance preservation using Gaussian density ramps in a beam-driven plasma wakefield accelerator
Authors: Litos M. D. , Ariniello R. , Doss C. E. , Hunt-Stone K. , Cary J. R.
Published: June 2019

A current challenge that is facing the plasma wakefield accelerator (PWFA) community is transverse beam emittance preservation. This can be achieved by balancing the natural divergence of the beam against the strong focusing force provided by the PWFA plasma source in a scheme referred to as beam matching. One method to accomplish beam matching is through the gradual focusing of a beam with a plasma density ramp leading into the bulk plasma. Here, the beam dynamics in a Gaussian plasma density ramp are considered, and an empirical formula is identified that gives the ramp length and beam vacuum waist location needed to achieve near-perfect matching. The method uses only the beam vacuum waist beta function as an input. Numerical studies show that the Gaussian ramp focusing formula is robust for beta function demagnification factors spanning more than an order of magnitude with experimentally favourable tolerances for future PWFA research facilities.

This article is part of the Theo Murphy meeting issue ‘Directions in particle beam-driven plasma wakefield acceleration’.