bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained depletion of FXIII-A by inducing acquired FXIII-B deficiency
Authors: Strilchuk Amy W. , Meixner Scott C. , Leung Jerry , Safikhan Nooshin S. , Kulkarni Jayesh A. , Russell Hannah M. , van der Meel Roy , Sutherland Michael R. , Owens A. Phillip , Palumbo Joseph S. , Conway Edward M. , Pryzdial Edward L. G. , Cullis Pieter R. , Kastrup Christian J.
Published: December 2020

The activated form of coagulation factor XIII (FXIII-A2B2), FXIII-A*, is a hemostatic enzyme essential for inhibiting fibrinolysis by irreversibly crosslinking fibrin and antifibrinolytic proteins. Despite its importance, there are no modulatory therapeutics. Guided by the observation that humans deficient in FXIII-B have reduced FXIII-A without severe bleeding, we hypothesized that a suitable small interfering RNA (siRNA) targeting hepatic FXIII-B could safely decrease FXIII-A. Here we show that knockdown of FXIII-B with siRNA in mice and rabbits using lipid nanoparticles resulted in a sustained and controlled decrease in FXIII-A. The concentration of FXIII-A in plasma was reduced by 90% for weeks after a single injection and for more than 5 months with repeated injections, whereas the concentration of FXIII-A in platelets was unchanged. Ex vivo, crosslinking of α2-antiplasmin and fibrin was impaired and fibrinolysis was enhanced. In vivo, reperfusion of carotid artery thrombotic occlusion was also enhanced. Re-bleeding events were increased after challenge, but blood loss was not significantly increased. This approach, which mimics congenital FXIII-B deficiency, provides a potential pharmacologic and experimental tool to modulate FXIII-A2B2 activity.
Building a transgenic sexing
strain for genetic control of the Australian sheep blow fly Lucilia cuprina using two lethal
effectors
Authors: Yan Ying , Scott Maxwell J.
Published: December 2020

Background

The sterile insect technique (SIT) has been
successfully used in many pest management programs worldwide.
Some SIT programs release both sexes due to the lack of genetic
sexing strains or efficient sex separation methods but sterile
females are ineffective control agents. Transgenic sexing
strains (TSS) using the tetracycline-off control system have
been developed in a variety of insect pests, from which females
die by either of two commonly used lethal effectors:
overexpression of the transcription factor tetracycline transactivator (tTA)
or ectopic expression of a proapoptotic gene, such as head involution defective
(hid). The lethality from
tTA overexpression is thought to be due to “transcriptional
squelching”, while hid causes
lethality by induction of apoptosis. This study aims to create
and characterize a TSS of Lucilia
cuprina, which is a major pest of sheep, by
combining both lethal effectors in a single transgenic
strain.

Results

Here a stable TSS of L.
cuprina (DH6) that carries two lethal effectors
was successfully generated, by crossing FL3#2 which carries a
female-specific tTA overexpression cassette, with EF1#12 which
carries a tTA-regulated LshidAla2 cassette. Females with
one copy of the FL3#2 transgene are viable but up to 99.8% of
homozygous females die at the pupal stage when raised on diet
that lacks tetracycline. Additionally, the female lethality of
FL3#2 was partially repressed by supplying tetracycline to the
parental generation. With an additional LshidAla2 effector, the female
lethality of DH6 is 100% dominant and cannot be repressed by
maternal tetracycline. DH6 females die at the late-larval stage.
Several fitness parameters important for mass rearing such as
hatching rate, adult emergence and sex ratio were comparable to
those of the wild type strain.

Conclusions

Compared to the parental FL3#2 strain, the DH6
strain shows stronger female lethality and lethality occurs at
an earlier stage of development. The combination of two
tTA-dependent lethal effectors could improve strain stability
under mass rearing and could reduce the risk of resistance in
the field if fertile males are released. Our approach could be
easily adapted for other pest species for an efficient, safe and
sustainable genetic control program.
The experiences of care managers and rehabilitation coordinators of a primary care intervention to promote return to work for patients with common mental disorders: a qualitative study
Authors: Petersson Eva-Lisa , Törnbom Karin , Hange Dominique , Nejati Shabnam , Jerlock Margareta , Wikberg Carl , Björkelund Cecilia , Svenningsson Irene
Published: December 2020

Background

In an earlier study, PRIM-CARE RCT, a care manager implementation at the primary care centre showed improved return to work and reduced sick leave for patients with CMD. To further improve return to work, the project Co-Work-Care added a person-centered dialogue meeting between the patient, the employer and the rehabilitation coordinator, preceded by an increased collaboration between care manager, rehabilitation coordinator and GP. In this first qualitative study of the Co-Work-Care project, we explored how care managers and rehabilitation coordinators experienced the Co-Work-Care model. The purpose of this study was to explore care managers’ and rehabilitation coordinators’ perceptions and experiences of a close collaboration and the use of the person-centred dialogue meeting.

Methods

From an ongoing RCT with 20 primary care centres, care managers (CMs) (n = 13) and rehabilitation coordinators (RCs) (n = 12) participated in a qualitative study with focus groups. The study was conducted in the primary health care in a Swedish region. The data was analysed with Systematic Text Condensation by Malterud.

Results

Seven codes describing the participants’ experiences of the Co-Work-Care model were identified: 1) The importance of collaboration at the primary care centre, 2) Collaboration and division of roles between the RC and the CM, 3) Collaboration with the General practitioner (GP), 4) The person-centred dialogue meeting, 5) Initiating the person-centred dialogue meeting, 6) The person-centred dialogue meeting to improve collaboration with the employer, and 7) The person-centred dialogue meeting to teach about the return to work process.

Conclusion

The increased collaboration within the Co-Work-Care model created a common picture and understanding of the patient’s situation. The person-centred dialogue meeting in the rehabilitation process became a bridge between the employer and the patient.

Trial registration

NCT03250026 (registered August 15, 2017).
Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
Authors: Freytag Morton , Kluth Martina , Bady Elena , Hube-Magg Claudia , Makrypidi-Fraune Georgia , Heinzer Hans , Höflmayer Doris , Weidemann Sören , Uhlig Ria , Huland Hartwig , Graefen Markus , Bernreuther Christian , Wittmer Corinna , Tsourlakis Maria Christina , Minner Sarah , Dum David , Hinsch Andrea , Luebke Andreas M. , Simon Ronald , Sauter Guido , Schlomm Thorsten , Möller Katharina
Published: December 2020

Background

Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis.

Methods

A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2.

Results

Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features.

Conclusions

Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.
COVID-19 and children with Down syndrome: is there any real reason to worry? Two case reports with severe course
Authors: Kantar Ahmad , Mazza Angelo , Bonanomi Ezio , Odoni Marta , Seminara Manuela , Verde Ilaria Dalla , Lovati Camillo , Bolognini Stefania , D’Antiga Lorenzo
Published: December 2020

Background

Down syndrome (DS) is characterized by a series of immune dysregulations, of which interferon hyperreactivity is important, as it is responsible for surging antiviral responses and the possible initiation of an amplified cytokine storm. This biological condition is attributed to immune regulators encoded in chromosome 21. Moreover, DS is also characterized by the coexistence of obesity and cardiovascular and respiratory anomalies, which are risk factors for coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Case presentation

A total of 55 children were admitted to the pediatric ward in Bergamo, between February and May 2020 for COVID-19. Here, we describe the cases of two children with DS and a confirmed COVID-19 diagnosis who had a severe course. In addition, both cases involved one or more comorbidities, including cardiovascular anomalies, obesity, and/or obstructive sleep apnea.

Conclusions

Our observations indicate that children with DS are at risk for severe COVID-19 disease course.
Cardiovascular implications of COVID-19 versus influenza infection: a review
Authors: Khan Muhammad Shahzeb , Shahid Izza , Anker Stefan D. , Solomon Scott D. , Vardeny Orly , Michos Erin D. , Fonarow Gregg C. , Butler Javed
Published: December 2020

Background

Due to the overlapping clinical features of coronavirus disease 2019 (COVID-19) and influenza, parallels are often drawn between the two diseases. Patients with pre-existing cardiovascular diseases (CVD) are at a higher risk for severe manifestations of both illnesses. Considering the high transmission rate of COVID-19 and with the seasonal influenza approaching in late 2020, the dual epidemics of COVID-19 and influenza pose serious cardiovascular implications. This review highlights the similarities and differences between influenza and COVID-19 and the potential risks associated with coincident pandemics.

Main body

COVID-19 has a higher mortality compared to influenza with case fatality rate almost 15 times more than that of influenza. Additionally, a significantly increased risk of adverse outcomes has been noted in patients with CVD, with ~ 15 to 70% of COVID-19 related deaths having an underlying CVD. The critical care need have ranged from 5 to 79% of patients hospitalized due to COVID-19, a proportion substantially higher than with influenza. Similarly, the frequency of vascular thrombosis including deep venous thrombosis and pulmonary embolism is markedly higher in COVID-19 patients compared with influenza in which vascular complications are rarely seen. Unexpectedly, while peak influenza season is associated with increased cardiovascular hospitalizations, a decrease of ~ 50% in cardiovascular hospitalizations has been observed since the first diagnosed case of COVID-19, owing in part to deferred care.

Conclusion

In the coming months, increasing efforts towards evaluating new interventions will be vital to curb COVID-19, especially as peak influenza season approaches. Currently, not enough data exist regarding co-infection of COVID-19 with influenza or how it would progress clinically, though it may cause a significant burden on an already struggling health care system. Until an effective COVID-19 vaccination is available, high coverage of influenza vaccination should be of utmost priority.
Donor-intrinsic variables determine mobilization efficiency: analyses from a cohort of sixty twice-mobilized stem cell donors
Authors: Kim-Wanner Soo-Zin , Lee Seo-Youn , Seifried Erhard , Bonig Halvard
Published: December 2020

Background

Healthy volunteer registry donors have become the backbone of stem cell transplantation programs. While most registrants will never become actual donors, a small minority are called upon twice, most commonly for the same patient because of poor graft function. Anecdotal evidence provides no hard reasons to disallow second-time mobilized apheresis, but few centers have treated enough two-time donors for definitive conclusions. Moreover, for reasons unknown, the efficiency of G-CSF varies greatly between donations.

Methods

Comparison of outcomes of first vs. second donations can formally confirm G-CSF responsiveness as intrinsically, likely genetically, determined. In our database, we identified 60 donors (1.3%) who received two cycles of G-CSF 24 days to 4 years apart and systematically compared mobilization outcomes.

Results

First and second mobilization and collection proceeded without severe or unusual adverse effects. First-time mobilization efficiency was highly predictive of second-time mobilization. Neither mobilization efficiency nor time lag between donations affected the similarity of first- and second-time mobilization outcomes.

Conclusions

With the caveat that only donors with an unremarkable first donation were cleared for a second, our data indicate that a second donation is feasible, equally tolerable as a first donation, and efficient. Moreover, the data strongly support the notion of donor-intrinsic variables dictating mobilization response and argue against relevant damage to the stem cell compartment during mobilization with rhG-CSF.
Assessment of changes in cardiopulmonary resuscitation practices and outcomes on 1005 victims of out-of-hospital cardiac arrest during the COVID-19 outbreak: registry-based study
Authors:   on behalf of the GR-RéAC, Baert Valentine , Jaeger Deborah , Hubert Hervé , Lascarrou Jean-Baptiste , Debaty Guillaume , Chouihed Tahar , Javaudin François
Published: December 2020

Background

The COVID-19 outbreak requires a permanent adaptation of practices. Cardiopulmonary resuscitation (CPR) is also involved and we evaluated these changes in the management of out-of-hospital cardiac arrest (OHCA).

Methods

OHCA of medical origins identified from the French National Cardiac Arrest Registry between March 1st and April 31st 2020 (COVID-19 period), were analysed. Different resuscitation characteristics were compared with the same period from the previous year (non-COVID-19 period).

Results

Overall, 1005 OHCA during the COVID-19 period and 1620 during the non-COVID-19 period were compared. During the COVID-19 period, bystanders and first aid providers initiated CPR less frequently (49.8% versus 54.9%; difference, − 5.1 percentage points [95% CI, − 9.1 to − 1.2]; and 84.3% vs. 88.7%; difference, − 4.4 percentage points [95% CI, − 7.1 to − 1.6]; respectively) as did mobile medical teams (67.3% vs. 75.0%; difference, − 7.7 percentage points [95% CI, − 11.3 to − 4.1]). First aid providers used defibrillators less often (66.0% vs. 74.1%; difference, − 8.2 percentage points [95% CI, − 11.8 to − 4.6]). Return of spontaneous circulation (ROSC) and D30 survival were lower during the COVID-19 period (19.5% vs. 25.3%; difference, − 5.8 percentage points [95% CI, − 9.0 to − 2.5]; and 2.8% vs. 6.4%; difference, − 3.6 percentage points [95% CI, − 5.2 to − 1.9]; respectively).

Conclusions

During the COVID-19 period, we observed a decrease in CPR initiation regardless of whether patients were suspected of SARS-CoV-2 infection or not. In the current atmosphere, it is important to communicate good resuscitation practices to avoid drastic and lasting reductions in survival rates after an OHCA.
Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease
Authors: Razazi Keyvan , Arrestier Romain , Haudebourg Anne Fleur , Benelli Brice , Carteaux Guillaume , Decousser Jean‑Winoc , Fourati Slim , Woerther Paul Louis , Schlemmer Frederic , Charles-Nelson Anais , Botterel Francoise , de Prost Nicolas , Mekontso Dessap Armand
Published: December 2020

Background

Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited.

Methods

We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).

Results

We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14–2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization.

Conclusions

In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.
Role of the adaptive immune response in sepsis
Authors: Brady Jack , Horie Shahd , Laffey John G.
Published: December 2020

Sepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it has become a global cause for concern. Advances in patient care and management now mean that most patients survive the initial hyper-inflammatory phase of sepsis but progress to a later immunosuppressed phase, where 30% of patients die due to secondary infection. Deficits in the adaptive immune response may play a major role in sepsis patient mortality. The adaptive immune response involves a number of cell types including T cells, B cells and dendritic cells, all with immunoregulatory roles aimed at limiting damage and returning immune homeostasis after infection or insult. However, in sepsis, adaptive immune cells experience cell death or exhaustion, meaning that they have defective effector and memory responses ultimately resulting in an ineffective or suppressed immune defence. CD4+ T cells seem to be the most susceptible to cell death during sepsis and have ensuing defective secretory profiles and functions. Regulatory T cells seem to evade apoptosis and contribute to the immune suppression observed with sepsis. Preclinical studies have identified a number of new targets for therapy in sepsis including anti-apoptotic agents and monoclonal antibodies aimed at reducing cell death, exhaustion and maintaining/restoring adaptive immune cell functions. While early phase clinical trials have demonstrated safety and encouraging signals for biologic effect, larger scale clinical trial testing is required to determine whether these strategies will prove effective in improving outcomes from sepsis.
Continuous external negative pressure improves oxygenation and respiratory mechanics in Experimental Lung Injury in Pigs – A pilot proof-of-concept trial
Authors: Scharffenberg Martin , Wittenstein Jakob , Herzog Moritz , Tauer Sebastian , Vivona Luigi , Theilen Raphael , Bluth Thomas , Kiss Thomas , Koch Thea , Fiorentino Giuseppe , de Abreu Marcelo Gama , Huhle Robert
Published: December 2020

Background

Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases the caudal end-expiratory transpulmonary pressure depending on positive end-expiratory pressure (PEEP) in lung-injured pigs. Eight pigs were anesthetised and mechanically ventilated in the supine position. Pressure sensors were placed in the left pleural space, and a lung injury was induced by saline lung lavages. A CENP shell was placed at the abdomen and thorax (randomised order), and animals were ventilated with PEEP 15, 7 and zero cmH2O (15 min each). On each PEEP level, CENP of − 40, − 30, − 20, − 10 and 0 cmH2O was applied (3 min each). Respiratory and haemodynamic variables were recorded. Electrical impedance tomography allowed assessment of centre of ventilation.

Results

Compared to positive pressure ventilation alone, the caudal transpulmonary pressure was significantly increased by CENP of ≤ 20 cmH2O at all PEEP levels. CENP of – 20 cmH2O reduced the mean airway pressure at zero PEEP (P = 0.025). The driving pressure decreased at CENP of ≤ 10 at PEEP of 0 and 7 cmH2O (P < 0.001 each) but increased at CENP of – 30 cmH2O during the highest PEEP (P = 0.001). CENP of – 30 cmH2O reduced the mechanical power during zero PEEP (P < 0.001). Both elastance (P < 0.001) and resistance (P < 0.001) were decreased at CENP ≤ 30 at PEEP of 0 and 7 cmH2O. Oxygenation increased at CENP of ≤ 20 at PEEP of 0 and 7 cmH2O (P < 0.001 each). Applying external negative pressure significantly shifted the centre of aeration towards dorsal lung regions irrespectively of the PEEP level. Cardiac output decreased significantly at CENP -20 cmH2O at all PEEP levels (P < 0.001). Effects on caudal transpulmonary pressure, elastance and cardiac output were more pronounced when CENP was applied to the abdomen compared with the thorax.

Conclusions

In this lung injury model in pigs, CENP increased the end-expiratory caudal transpulmonary pressure. This lead to a shift of lung aeration towards dependent zones as well as improved respiratory mechanics and oxygenation, especially when CENP was applied to the abdomen as compared to the thorax. CENP values ≤ 20 cmH2O impaired the haemodynamics.
Alkaline phosphatase in pulmonary inflammation—a translational study in ventilated critically ill patients and rats
Authors:   for the BASIC study investigators, Juschten Jenny , Ingelse Sarah A. , Bos Lieuwe D. J. , Girbes Armand R. J. , Juffermans Nicole P. , van der Poll Tom , Schultz Marcus J. , Tuinman Pieter Roel
Published: December 2020

Background

Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects.

Aim

To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of recombinant AP on pulmonary inflammation in a well-established lung injury model in rats

Methods

AP activity was determined and compared with levels of various inflammatory mediators in bronchoalveolar lavage fluid (BALF) samples obtained from critically ill patients within 2 days of start of invasive ventilation. The endpoints of this part of the study were the correlations between AP activity and markers of inflammation, i.e., interleukin (IL)-6 levels in BALF. In RccHan Wistar rats, lung injury was induced by intravenous administration of 10 mg/kg lipopolysaccharide, followed by ventilation with a high tidal volume for 4 h. Rats received either an intravenous bolus of 1500 IU/kg recombinant AP or normal saline 2 h after intravenous LPS administration, right before start of ventilation. Endpoints of this part of the study were pulmonary levels of markers of inflammation, including IL-6, and markers of endothelial and epithelial dysfunction.

Results

BALF was collected from 83 patients; 10 patients had mild ARDS, and 15 had moderate to severe ARDS. AP activity correlated well with levels of IL-6 (r = 0.70), as well as with levels of other inflammatory mediators. Pulmonary AP activity between patients with and without ARDS was comparable (0.33 [0.14–1.20] vs 0.55 [0.21–1.42] U/L; p = 0.37). Animals with acute lung injury had markedly elevated pulmonary AP activity compared to healthy controls (2.58 [2.18–3.59] vs 1.01 [0.80–1.46] U/L; p < 0.01). Intravenous administration of recombinant AP did neither affect pulmonary inflammation nor endothelial and epithelial dysfunction.

Conclusions

In ventilated critically ill patients, pulmonary AP activity correlates well with markers of pulmonary inflammation, such as IL-6 and IL-8. In animals with lung injury, pulmonary AP activity is elevated. Administration of recombinant AP does not alter pulmonary inflammation and endothelial or epithelial dysfunction in the acute phase of a murine lung injury model.
Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial
Authors: van der Hoeven Sophia , Ball Lorenzo , Constantino Federico , van Meenen David M. , Pelosi Paolo , Beenen Ludo F. , Schultz Marcus J. , Paulus Frederique ,   for the NEBULAE-investigators
Published: December 2020

Background

Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients.

Results

In this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33).

Conclusion

In adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube.

Trial registration Clinicaltrials.gov Identifier: NCT02159196
The effects of tidal volume size and driving pressure levels on pulmonary complement activation: an observational study in critically ill patients
Authors:   for the BASIC–study group, de Beer Friso M. , Wieske Luuk , van Mierlo Gerard , Wouters Diana , Zeerleder Sacha , Bos Lieuwe D. , Juffermans Nicole P. , Schultz Marcus J. , van der Poll Tom , Lagrand Wim K. , Horn Janneke
Published: December 2020

Background

Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury.

Aims and methods

This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings, tidal volume (VT) and driving pressure (ΔP), in critically ill patients under invasive ventilation. A miniature bronchoalveolar lavage (BAL) was performed for determination of pulmonary levels of C5a, C3b/c, and C4b/c. The primary endpoint was the correlation between BAL fluid (BALF) levels of C5a and VT and ΔP. Levels of complement activation products were also compared between patients with and without ARDS or with and without pneumonia.

Results

Seventy-two patients were included. Median time from start of invasive ventilation till BAL was 27 [19 to 34] hours. Median VT and ΔP before BAL were 6.7 [IQR 6.1 to 7.6] ml/kg predicted bodyweight (PBW) and 15 [IQR 11 to 18] cm H2O, respectively. BALF levels of C5a, C3b/c and C4b/c were neither different between patients with or without ARDS, nor between patients with or without pneumonia. BALF levels of C5a, and also C3b/c and C4b/c, did not correlate with VT and ΔP. Median BALF levels of C5a, C3b/c, and C4b/c, and the effects of VT and ΔP on those levels, were not different between patients with or without ARDS, and in patients with or without pneumonia.

Conclusion

In this cohort of critically ill patients under invasive ventilation, pulmonary levels of complement activation products were independent of the size of VT and the level of ΔP. The associations were not different for patients with ARDS or with pneumonia. Pulmonary complement activation does not seem to play a major role in VILI, and not even in lung injury per se, in critically ill patients under invasive ventilation.
Retrospective Analysis of Peri-Intubation Hypoxemia During the Coronavirus Disease 2019 Epidemic Using a Protocol for Modified Airway Management
Authors: Madhok Jai , Vogelsong Melissa A. , Lee Tiffany C. , Wilson Jennifer G. , Mihm Frederick
Published: December 2020

This single-center retrospective study evaluated a protocol for the intubation of patients with confirmed or suspected coronavirus disease 2019 (COVID-19). Twenty-one patients were intubated, 9 of whom were found to have COVID-19. Adherence to the airway management protocol was high. COVID-19 patients had lower peripheral capillary oxygen saturation by pulse oximetry (Spo
2) nadirs during intubation (Spo
2, 73% [72%–77%] vs 89% [86%–94%], P = .024), and a greater percentage experienced severe hypoxemia defined as Spo
2 ≤80% (89% vs 25%, P = .008). The incidence of severe hypoxemia in COVID-19 patients should be considered in the development of guidelines that incorporate high-flow nasal cannula and noninvasive positive pressure ventilation.
What’s the Matter with Labor History?
Authors: Fraser Max
Published: December 2020

The events of September 11 changed American politics in ways that continue to reverberate today—including the way we think and talk about working-class conservatism. The author describes how the aftermath of 9/11 shaped his own developing interests in American labor and working-class history, and how it continues to shape his research agenda as a scholar of postwar America.
First isolation of Mycobacterium bovis SIT 482 BOV from beef cattle in Turkey
Authors: AVSEVER M.L. , ÇAVUŞOĞLU C. , ÇAMKERTEN I.
Published: December 2020

Bovine tuberculosis is a zoonotic disease which should be emphasized in our country as in many countries. A large number of genotypes have been revealed by spoligotyping method of M. bovis in the world. M. bovis SIT 482. BOV is one of these genotypes and it is also M. bovis genotype in which BCG vaccine is administered in humans. The BCG vaccine is obtained through multiple passages of this genotype. However, this genotype, like other genotypes, can cause serious infections in humans and animals. There are data on the isolation of M. bovis SIT 482 BOV from animal and human tuberculosis cases in the world. In our country, the isolation of this genotype has been reported only in humans and no data have been found in the animals. In this study, M. bovis SIT 482. BOV was isolated from the samples of six cattle with internal organ samples obtained from licensed slaughterhouses in Aksaray. While isolation is carried out with BACTEC MGIT 960 liquid media, spoligotyping was carried out according to the manufacturer’s with kit (Isogen LifeScience, The Netherlands). This study aims to report M. bovis SIT 482 BOV from cattle in Turkey for the first time, to draw attention a very limited number reported in M. bovis cases in Turkey, highlight the importance of genotyping of tuberculosis factors and contribute to epidemiological studies. These and similar studies will contribute to the creation of genetic maps for eradication of M. bovis from cattle in our country. The study was also conducted to investigate whether M. bovis SIT 482. BOV isolated from cattle in Aksaray province is BCG strain or another strain giving the same pattern.
Seroprevalence of Coxiella burnetii among ewes and associated risk factors in Constantine (Northeastern Algeria)
Authors: HIRECHE S. , AGABOU A. , BOUAZIZ Ο.
Published: December 2020

Q fever is a zoonotic disease caused by the rickettsia-like Coxiella burnetii and leads to abortions and decreased reproductive performances in domestic ruminants. A serological survey, using ELISA test, was conducted to assess the prevalence of this infection in 226 ewes belonging to 39 flocks localized in Constantine (North-eastern Algeria). A pretested questionnaire has been submitted to farmers/shepherds to collect information related to relevant risk factors. Results revealed the presence of C. burnetii antibodies in 12.4% (95% CI: 8.08%−16.72%) of individual animals while 35.9% (95% CI: 21.20%−52.82%) of sampled flocks accounted at least one seropositive ewe. Significant causative associations were observed for origin of animals (χ2=14.29, P=0.001), vaccination against enterotoxaemia (χ2=12.12, P=0.002) and pox (χ2=5.30, P=0.025), access to the farm by foreign visitors (χ2=10.87, P=0.004), farmers/shepherds’ visits to other farms (χ2=6.31, P=0.021), disinfection frequency (χ2=7.98, P=0.046), pest infestation within farms (χ2=9.55, P=0.049) and abortion history (χ2=5.54, P=0.029). This recorded prevalence of Coxiella infection would indicate a possible responsibility of this agent in causing abortion and reproductive failures in the tested flocks. Implementing active surveillance programs and further investigations using more accurate analyses and including large samples of more animal species from several provinces are needed to eluci date the real occurrence and dynamics of this infection in the national livestock.
The evolving nature of work in the Agri-foodstuffs Sector. The impact of Precision Agriculture and the necessity of acquiring new skills through Lifelong Learning
Authors: Staboulis Miltiadis , Kostas Antonios
Published: December 2020

The article focuses on the necessity of acquiring a combination of “vertical” and “horizontal” skills, which are of vital importance in the new production management processes and work in the Agri-foodstuffs sector, so as to ensure an efficient relationship between the human resources and the current technological applications. The aim of this paper is to research and pinpoint the opportunities and weaknesses of the required new skills in relation to new technologies in the wider context of the agrifood labour market, and to which extent these skills can feasibly be developed through Lifelong Learning Educational Programmes. The research method of this paper is a qualitative “focus groups” interview method.
Study protocol for Post Pregnancy Family Planning Choices, an operations research study examining the effectiveness of interventions in the public and private sectors in Indonesia and Kenya
Authors: Charurat Elaine , Kennedy Sara , Qomariyah Siti , Schuster Anne , Christofield Megan , Breithaupt Lindsay , Kariuki Emmah , Muthamia Michael , Kabue Mark , Omanga Eunice , Stekelenburg Jelle
Published: December 2020

Background: Global evidence suggests many postpartum and postabortion women have an unmet need for family planning (FP) after delivery or receiving care following loss of a pregnancy. Post Pregnancy Family Planning Choices, an operations research study, aims to examine the effectiveness of a package of postpregnancy FP interventions, inclusive of postpartum and postabortion FP. The interventions are being implemented in selected public and private facilities in Indonesia and Kenya and focus on quality FP counseling and service provision prior to discharge. This manuscript presents the study protocol, documenting how the study team intends to determine key factors that influence uptake of postpregnancy FP.

Methods: This is a multi-country, quasi-experimental three-year operations research study in Brebes and Batang Districts of Indonesia and Meru and Kilifi Counties of Kenya. Quantitative and qualitative data is collected longitudinally through interviews and health facility assessments at multiple time points. Data is gathered from 22 health facilities; 8,796 antenatal, postpartum, and postabortion clients; and key informants at national, subnational, facility, and community levels. Quantitative study data is collected and managed using REDCap (Research Electronic Data Capture). Once data are thoroughly cleaned and reviewed, regression models and multilevel analyses will explore quantitative data. Qualitative study data is collected using audio recordings and transcribed to Microsoft Word, then analyzed using ATLAS.ti. Qualitative datasets will be analyzed using grounded theory methods.

Discussion: The ultimate goals of the study are to generate and disseminate actionable evidence of positive drivers, barriers, and activities that do not yield results with regard to increasing postpregnancy FP programmatic activities, and to institutionalize postpregnancy FP in the public and private sectors in Indonesia and Kenya. We hope these learnings and experience will contribute to global efforts to advance and scale up postpregnancy FP in similar settings beyond these two countries.

Trial registration: ClinicalTrials.gov NCT03333473
The feasibility of implementing an exercise programme for deconditioned cancer survivors in a national cancer centre: FIXCAS Study
Authors: Devenney Kate , Murphy Niamh , Ryan Ronan , Grant Clíona , Kennedy John , Manecksha Rustom P. , Sheils Orla , McNeely Margaret L. , Hussey Juliette , Sheill Grainne
Published: December 2020

Introduction: As both the number of cancer survivors and the length of survival time are increasing, long-term health issues related to cancer and its treatment are becoming more prevalent. Research suggests that exercise can mitigate several negative health consequences in cancer survivors and improve physical function and quality of life. Multi-modal exercise interventions have been proposed as a cornerstone for survivorship care. However, studies evaluating exercise programmes within the Irish population are lacking.

Purpose: To evaluate the introduction, implementation and acceptability of a multi-modal exercise rehabilitation programme for deconditioned cancer survivors in a real-world, standard practice setting.

Methods and analysis: In this single-arm prospective feasibility study, cancer survivors (n=40) will undergo a 10-week multi-modal exercise programme. The study population will comprise of cancer survivors attending outpatient services in an Irish national cancer centre. Participants will be aged 18 or older and have completed treatment with curative intent. Feasibility will be evaluated in terms of recruitment, adherence and compliance to the programme. Secondary outcomes will examine physical function and quality of life measures. In addition, the acceptability of the programme will be assessed through stakeholder feedback.

Ethics and dissemination: Ethical approval through the St. James’s Hospital and Tallaght University Hospital Research and Ethics Committee is currently pending. The study results will be used to optimise the intervention content and may serve as the foundation for a larger definitive trial. Results will be disseminated through peer-review journals, congresses and relevant clinical groups. Trial registration: ClinicalTrials.gov NCT04026659 (19/07/19)
A living mapping review for COVID-19 funded research projects: three-month update
Authors: Norton Alice , Bucher Adrian , Antonio Emilia , Advani Nicole , Grund Henrike , Mburu Sheila , Clegg Emma , Scott Laura , Boily-Larouche Genevieve , Lay A. Morgan , Carson Gail , Tufet Bayona Marta
Published: December 2020

Background:The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims.

Methods:The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15thOctober 2020 the database contains 5,084 projects, funded by 71 funders, taking place across 134 countries representing an investment of at least $1.7 billion. To our knowledge it is one of the most comprehensive databases, covering a wide breadth of research disciplines. The database is aligned to the World Health Organisation (WHO) Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers.

This living mapping review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio.

Results:In this three-month update analysis we provide an updated detailed descriptive analysis of the database and focus our thematic analysis on research gaps, research areas in need of coordination, study populations and research locations (with a focus on resource-limited countries).

Conclusions:This living mapping review will help both funders and researchers to prioritise resources to underfunded areas where there is greatest research need and facilitate further strategic collaboration.
Blockchain technology in elections: past, present and future
Authors: Alekseev Roman
Published: December 2020

The purpose of the research is to use blockchain technology in the electoral process. The study was conducted on the example of blockchain technologies used in elections in the United States, Canada, Australia, Sierra Leone, Switzerland, Spain, Russia and other countries. The methodological basis of the research is based on the methods of comparative analysis and component analysis of definitions. Empirical methods of expert assessment and interviewing were used. The pros and cons of blockchain technologies and the possibility of using this innovative technology in elections of different levels are revealed. The advantages of inclusive blockchain technology include the mobility and accessibility of voting; minimizing the costs of organizing and conducting elections; de-bureaucratization by reducing the staff of election commissions; the possibility of excluding the impact on voters from participants in the electoral process; reducing the time for processing ballots and determining the results of voting; increasing the level of trust in electoral procedures on the part of citizens who usually do not participate in voting. Among the disadvantages of blockchain technologies, we can highlight: technical failures and hacker cyber-attacks; the possibility of hackers using data about voters, in case of hacking electronic databases; violation of the secrecy of voting.
Russia in the UN: imperatives of disarmament vectors
Authors: Mizin V. , Sevost'yanov P. , Matyukhin A.
Published: December 2020

The main purpose of this article is to study the efforts of the United Nations as a legitimate platform at the global level, which has tools of an international legal nature to maintain peace, stability and security in arms control issues, in the field of disarmament and non-proliferation of weapons of mass destruction (WMD). The article examines the history of long-term activities of Soviet and Russian diplomacy in this area, offers solutions and scenarios for building new approaches in Russian foreign policy in this area. When preparing the article, a set of different methods was used: the main technique was the complex application of different methods – system, historical and problem analysis, along with the principles of logical interpretation. The article highlights the role and importance of the most important international UN documents in the field of disarmament, adopted with the active participation of Soviet and Russian diplomacy, develops the concept of inadmissibility of diluting the main elements and powers of the UN system, and also gives specific recommendations for their prevention. The authors conclude that the end of the cold war did not lead to a stable and equal system, safe for its participants, and the new rivalry of the leading powers returned. In this regard, the perspective importance of the "nuclear five" format in the issues of arms control and disarmament processes is highlighted. The theoretical and, especially, practical significance of the work is determined by the high degree of relevance of this issue – at present, the architecture of security and control over nuclear weapons created over the past half century is disintegrating, which, according to the authors, requires a rethinking of the role of the UN in global processes.
Igneous Rock Associations 27. Chalcophile and Platinum Group Elements in the Columbia River Basalt Group: A Model for Flood Basalt Lavas
Authors: Reidel Stephen P. , Barnett D. Brent
Published: December 2020

The Columbia River Basalt Group is the youngest and best preserved continental Large Igneous Province on Earth. The 210,000 km3 of basaltic lavas were erupted between 16.6 and 5 Ma in the Pacific Northwest, USA. The peak of the eruptions occurred over a 700,000-year period when nearly 99% of the basalts consisting of the Steens, Imnaha, Picture Gorge, Grande Ronde and Wanapum Basalts were emplaced. In this study we examined the Platinum Group Elements (PGEs) Pt and Pd, and the chalcophile elements Cu and Zn in the Columbia River Basalt Group. The presence of Pt, Pd and Cu in the compositionally primitive Lower Steens, Imnaha and Picture Gorge Basalts suggests that the Columbia River Basalt Group magma was a fertile source for these elements. The PGEs are contained mainly in sulphides in the earliest formations based on their correlation with immiscible sulphides, sulphide minerals and chalcophile elements. Grande Ronde, Wanapum and Saddle Mountains Basalts are depleted in PGEs and chalcophile elements compared to earlier formations. Sulphur was saturated in many flows and much of it probably came from assimilation of cratonic rock from a thinned lithosphere. We propose a model where the presence or absence of PGEs and chalcophile elements results primarily from the interaction between an advancing plume head and the crust/lithosphere that it encountered. The early lavas erupted from a plume that had little interaction with the crust/lithosphere and were fertile. However, as the plume head advanced northward, it assimilated crustal/lithospheric material and PGE and chalcophile elements were depleted from the magma. What little PGE and chalcophile elements remained in the compositionally evolved and depleted Grande Ronde Basalt flows mainly were controlled by substitution in basalt minerals and not available for inclusion in sulphides.