Context.
Class II methanol masers are signposts of massive young stellar objects (MYSOs). Recent evidence shows that flares of these masers are driven by MYSO accretion bursts. Thus, maser monitoring ...can be used to identify such bursts which are hard to discover otherwise. Infrared observations reveal burst-induced changes in the spectral energy distribution (first and foremost a luminosity increase), which provide valuable information on a very intense phase of high-mass star formation.
Aims.
In mid-January 2019, flaring of the 6.7 GHz CH
3
OH maser (hereafter maser) of the MYSO G358.93-0.03 (hereafter G358) was reported. The international maser community initiated an extensive observational campaign which revealed extraordinary maser activity and yielded the detection of numerous new masering transitions. Interferometric imaging with the Atacama Large Millimeter/submillimeter Array and the Submillimeter Array resolved the maser emitting core of the star forming region and proved the association of the masers with the brightest continuum source (MM1), which hosts a hot molecular core. These observations, however, failed to detect a significant rise in the (sub)millimeter dust continuum emission. Therefore, we performed near-infrared (NIR) and far-infrared (FIR) observations to prove or disprove whether the CH
3
OH flare was driven by an accretion burst.
Methods.
NIR imaging with the Gamma-Ray Burst Optical/Near-infrared Detector has been acquired and integral-field spectroscopy with the Field-Imaging Far-Infrared Line Spectrometer (FIFI-LS) aboard the Stratospheric Observatory for Infrared Astronomy (SOFIA) was carried out on two occasions to detect possible counterparts to the (sub)millimeter sources and compare their photometry to archival measurements. The comparison of pre-burst and burst spectral energy distributions is of crucial importance to judge whether a substantial luminosity increase, caused by an accretion burst, is present and if it triggered the maser flare. Radiative transfer modeling of the spectral energy distribution (SED) of the dust continuum emission at multiple epochs provides valuable information on the bursting MYSO.
Results.
The FIR fluxes of MM1 measured with FIFI-LS exceed those from
Herschel
significantly, which clearly confirms the presence of an accretion burst. The second epoch data, taken about 16 months later, still show increased fluxes. Our radiative transfer modeling yielded major burst parameters and suggests that the MYSO features a circumstellar disk which might be transient. From the pre-burst, burst, and post-burst SEDs, conclusions on heating and cooling time-scales could be drawn. Circumstances of the burst-induced maser relocation have been explored.
Conclusions.
The verification of the accretion burst from G358 is another confirmation that Class II methanol maser flares represent an alert for such events. Thus, monitoring of these masers greatly enhances the chances of identifying MYSOs during periods of intense growth. The few events known to date already indicate that there is a broad range in burst strength and duration as well as environmental characteristics. The G358 event is the shortest and least luminous accretion burst known to date. According to models, bursts of this kind occur most often.
Antiviral treatment of immunocompromised patients with prolonged influenza virus infection can lead to multidrug resistance. This study reveals the selection of antiviral resistance mutations in ...influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient was treated with two courses of oseltamivir (5 days and 2 months, respectively), with the first course starting at symptom onset, and subsequently zanamivir (2 months and 10 days, respectively). Respiratory samples were investigated by Sanger and next generation sequencing (NGS) and, for NGS data, low-frequency-variant-detection analysis was performed. Neuraminidase-inhibition tests were conducted for samples isolated in Madin-Darby canine kidney cells. In a sample collected 15 days after the end of the first treatment with oseltamivir (Day 20 post-symptom onset), oseltamivir resistance was detected (mutation H275Y with 60.3% frequency by NGS). Day 149 when the patient had almost completed the second zanamivir treatment, mixes of the following resistance mutations were detected; H275Y(65.1%), I223R(9.2%), and E119G(89.6%), accompanied by additional mutations, showing a more complex viral population in the long-term treated patient. Two samples obtained on Day 151 from bronchoalveolar lavage (BAL) and nasopharyngeal swab, respectively, showed different mutation profiles, with a higher frequency of antiviral resistance mutations in BAL. The results emphasise the importance of timely antiviral resistance testing both for treatment of individual patients as well as for preventive measures to control the development and transmission of antiviral resistant viruses.
Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice.
To develop patient-oriented ...clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management.
Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations.
The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations.
This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.
Background
In randomized trials, it has been found that maternal influenza vaccination reduces influenza infections in both women and their infants. However, these trials have been performed in ...low‐resource settings, and evidence from high‐resource settings is limited.
Methods
Nested within a register‐based cohort of all women giving birth in Denmark between 2010 and 2016 (n = 357 810 births), we conducted two case–control studies using a test‐negative design of all pregnant women and their infants, respectively, tested for influenza virus with reverse transcriptase‐polymerase chain reaction. Influenza virus‐positive cases were matched (1:1) with influenza virus‐negative controls for calendar time and (gestational or infant) age at testing. The effectiveness of maternal immunization with trivalent inactivated influenza vaccine was estimated from the odds ratios of vaccination among cases versus controls using logistic regression with adjustment for potential confounders.
Results
Among 313 pregnant women positive for influenza virus, 16 (5.1%) were vaccinated; by comparison, 34 (10.9%) pregnant women were vaccinated among 313 matched influenza virus‐negative controls. The effectiveness of vaccination against laboratory‐confirmed influenza infection in pregnant women was 63.9% 95% confidence interval (CI), 29.1 to 81.6. Among 460 infants positive for influenza virus, 23 (5.0%) were offspring of women vaccinated during pregnancy; by comparison, 52 (11.3%) infants were the offspring of women vaccinated during pregnancy among 460 matched influenza virus‐negative controls. The effectiveness of maternal vaccination against laboratory‐confirmed influenza infection in infants younger than 6 months of age was 56.8% (95% CI, 25.0 to 75.1).
Conclusions
Seasonal trivalent inactivated influenza vaccination in pregnancy was associated with a statistically significant reduced risk of laboratory‐confirmed influenza infections in pregnant women and their infants in a high‐resource setting.
Treatment of injured donor lungs ex vivo to accelerate organ recovery and ameliorate reperfusion injury could have a major impact in lung transplantation. We have recently demonstrated a feasible ...technique for prolonged (12 h) normothermic ex vivo lung perfusion (EVLP). This study was performed to examine the impact of prolonged EVLP on ischemic injury. Pig donor lungs were cold preserved in Perfadex® for 12 h and subsequently divided into two groups: cold static preservation (CSP) or EVLP at 37°C with Steen™ solution for a further 12 h (total 24 h preservation). Lungs were then transplanted and reperfused for 4 h. EVLP preservation resulted in significantly better lung oxygenation (PaO2 531 ± 43 vs. 244 ± 49 mmHg, p < 0.01) and lower edema formation rates after transplantation. Alveolar epithelial cell tight junction integrity, evaluated by zona occludens‐1 protein staining, was disrupted in the cell membranes after prolonged CSP but not after EVLP. The maintenance of integrity of barrier function during EVLP translates into significant attenuation of reperfusion injury and improved graft performance after transplantation. Integrity of functional metabolic pathways during normothermic perfusion was confirmed by effective gene transfer and GFP protein synthesis by lung alveolar cells. In conclusion, EVLP prevents ongoing injury associated with prolonged ischemia and accelerates lung recovery.
Normothermic ex vivo lung perfusion provides improved post transplant lung function over static cold storage.
The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with ...rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1–G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A6) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.
Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) ...of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer’s dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)—a tract important to induce PAS-LTP—were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to ...warm. We present ice core isotopic measurements of methane (Δ
C, δ
C, and δD) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (<19 teragrams of methane per year, 95% confidence interval) and argue against similar methane emissions in response to future warming. Our results also indicate that methane emissions from biomass burning in the pre-Industrial Holocene were 22 to 56 teragrams of methane per year (95% confidence interval), which is comparable to today.
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