Transfusion thresholds and beyond

Comment on Liberal transfusion strategy improves survival in perioperative but not in critically ill patients. A meta-analysis of randomised trials. [Br J Anaesth. 2015

Ecosystem photosynthesis in land-surface models: a first-principles approach

Vegetation regulates land-atmosphere water and energy exchanges and is an essential component of land-surface models (LSMs). However, LSMs have been handicapped by assumptions that equate acclimated photosynthetic responses to environment with fast responses observable in the laboratory. These time scales can be distinguished by including specific representations of acclimation, but at the cost of further increasing parameter requirements. Here we develop an alternative approach based on optimality principles that predict the acclimation of carboxylation and electron-transport capacities, and a variable controlling the response of leaf-level carbon dioxide drawdown to vapour pressure deficit (VPD), to variations in growth conditions on a weekly to monthly time scale. In the “P model”, an optimality-based light-use efficiency model for gross primary production (GPP) on this time scale, these acclimated responses are implicit. Here they are made explicit, allowing fast and slow response time-scales to be separated and GPP to be simulated at sub-daily timesteps. The resulting model mimics diurnal cycles of GPP recorded by eddy-covariance flux towers in a temperate grassland and boreal, temperate and tropical forests, with no parameter changes between biomes. Best performance is achieved when biochemical capacities are adjusted to match recent midday conditions. This model suggests a simple and parameter-sparse method to include both instantaneous and acclimated responses within an LSM framework, with many potential applications in weather, climate and carbon - cycle modelling

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

A forecasting model to estimate the drop in blood supplies during the SARS-CoV-2 pandemic in Italy

Objectives: To estimate the number of actually Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infected blood donors applying a statistical forecasting model. Background: Following the outbreak of the SARS-CoV-2 epidemic, a drop in blood donation has been observed. It is crucial to determine the actual number of potential SARS-CoV-2-positive donors to define the measures and ensure adequate blood supply. Methods: The cumulative incidence of SARS-CoV-2 positivity, calculated on the general population, was applied to the donor population by estimating the number of positive subjects. The calculation model was validated by the linear interpolation method. The number of blood units actually discarded based on post-donation information was also taken into account. Results: Three months after the outbreak, 5322 donors were estimated to be positive for SARS-CoV-2 and were therefore potentially excluded from donation. A total of units of blood components were discarded following post donation information. The estimated number of donors deceased (180) and the number of clinically recovered individuals in the same period was also considered. Conclusion: This forecasting model can be used to obtain information on blood donors' involvement during future SARS-CoV-2 outbreaks, especially in case of changes concerning epidemiology, incidence by age bracket and geographical distribution and also for new outbreaks of emerging viruses

Deprotection of centromeric cohesin at meiosis II requires APC/C activity but not kinetochore tension

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes

Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: Complexity and vaccine implications

BackgroundFew studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM).MethodsWe described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II.ResultsMedian age was 44years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm(3) (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p=0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p=0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p=0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up.ConclusionsWe believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site

A MIQE-Compliant Real-Time PCR Assay for Aspergillus Detection

PMCID: PMC3393739This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Blood component therapy and coagulopathy in trauma: A systematic review of the literature from the trauma update group

Background Traumatic coagulopathy is thought to increase mortality and its treatment to reduce preventable deaths. However, there is still uncertainty in this field, and available literature results may have been overestimated. Methods We searched the MEDLINE database using the PubMed platform. We formulated four queries investigating the prognostic weight of traumatic coagulopathy defined according to conventional laboratory testing, and the effectiveness in reducing mortality of three different treatments aimed at contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios, fibrinogen, and tranexamic acid administration). Randomized controlled trials were selected along with observational studies that used a multivariable approach to adjust for confounding. Strict criteria were adopted for quality assessment based on a two-step approach. First, we rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Then, this rating was downgraded if other three criteria were not met: high reporting quality according to shared standards, absence of internal methodological and statistical issues not detailed by the GRADE system, and absence of external validity issues. Results With few exceptions, the GRADE rating, reporting and methodological quality of observational studies was "very low", with frequent external validity issues. The only two randomized trials retrieved were, instead, of high quality. Only weak evidence was found for a relation between coagulopathy and mortality. Very weak evidence was found supporting the use of fibrinogen administration to reduce mortality in trauma. On the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality reduction. This does not exclude lower mortality rates, which have not been investigated. The use of tranexamic acid in trauma was supported by "high" quality evidence according to the GRADE classification but was downgraded to "moderate" for external validity issues. Conclusions Tranexamic acid is effective in reducing mortality in trauma. The other transfusion practices we investigated have been inadequately studied in the literature, as well as the independent association between mortality and coagulopathy measured with traditional laboratory testing. Overall, in this field of research literature quality is poor

Gains and losses of coral skeletal porosity changes with ocean acidification acclimation

Ocean acidi\ufb01cation is predicted to impact ecosystems reliant on calcifying organisms, potentially reducing the socioeconomic bene\ufb01ts these habitats provide. Here we investigate the acclimation potential of stony corals living along a pH gradient caused by a Mediterranean CO2 vent that serves as a natural long-term experimental setting. We show that in response to reduced skeletal mineralization at lower pH, corals increase their skeletal macroporosity (features >10 micrometers) in order to maintain constant linear extension rate, an important criterion for reproductive output. At the nanoscale, the coral skeleton\u2019s structural features are not altered. However, higher skeletal porosity, and reduced bulk density and stiffness may contribute to reduce population density and increase damage susceptibility under low pH conditions. Based on these observations, the almost universally employed measure of coral biomineralization, the rate of linear extension, might not be a reliable metric for assessing coral health and resilience in a warming and acidifying ocean

Systematic review of the literature and evidence-based recommendations for antibiotic prophylaxis in trauma : results from an italian consensus of experts

Antibiotic prophylaxis is frequently administered in severe trauma. However, the risk of selecting resistant bacteria, a major issue especially in critical care environments, has not been sufficiently investigated. The aim of the present study was to provide guidelines for antibiotic prophylaxis for four different trauma-related clinical conditions, taking into account the risks of antibiotic-resistant bacteria selection, thus innovating previous guidelines in the field