Minimally invasive versus conventional aortic valve replacement: a propensity-matched study from the UK National Data

Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR).Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006-2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used.Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%-3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%-4.3%; P = 0.752]. One-year survival rates in the MIAVR and CAVR groups were 94.4% and 94.6%, respectively. There was no statistically significant difference in midterm survival (P = 0.677; hazard ratio, 0.90; 95% CI, 0.56-1.46). Median postoperative length of stay was lower in the MIAVR patients by 1 day (P = 0.009). The mean cumulative bypass time (94.8 vs 91.3 minutes; P = 0.333) and cross-clamp time (74.6 vs 68.4 minutes; P = 0.006) were longer in the MIAVR group; however, this was significant only in the cross-clamp time comparison.Minimally invasive aortic valve replacement is a safe alternative to CAVR with respect to operative and 1-year mortality and is associated with a shorter postoperative stay. Further studies are required in high-risk (logistic EuroSCORE > 10) patients to define the role of MIAVR

Affimer-Based Europium Chelates Allow Sensitive Optical Biosensing in a Range of Human Disease Biomarkers

The protein biomarker measurement has been well-established using ELISA (enzyme-linked immunosorbent assay), which offers good sensitivity and specificity, but remains slow and expensive. Certain clinical conditions, where rapid measurement or immediate confirmation of a biomarker is paramount for treatment, necessitate more rapid analysis. Biosensors offer the prospect of reagent-less, processing-free measurements at the patient’s bedside. Here, we report a platform for biosensing based on chelated Eu3+ against a range of proteins including biomarkers of cardiac injury (human myoglobin), stroke (glial fibrillary acidic protein (GFAP)), inflammation (C-reactive protein (CRP)) and colorectal cancer (carcinoembryonic antigen (CEA)). The Eu3+ ions are chelated by modified synthetic binding proteins (Affimers), which offer an alternative targeting strategy to existing antibodies. The fluorescence characteristics of the Eu3+ complex with modified Affimers against human myoglobin, GFAP, CRP and CEA were measured in human serum using λex = 395 nm, λem = 590 and 615 nm. The Eu3+-Affimer based complex allowed sensitive detection of human myoglobin, GFAP, CRP and CEA proteins as low as 100 fM in (100-fold) diluted human serum samples. The unique dependence on Eu3+ fluorescence in the visible region (590 and 615 nm) was exploited in this study to allow rapid measurement of the analyte concentration, with measurements in 2 to 3 min. These data demonstrate that the Affimer based Eu3+ complexes can function as nanobiosensors with potential analytical and diagnostic applications

Misconceiving patient reported outcome measures (PROMs) as primarily a reporting requirement rather than a quality improvement tool: perceptions of independent healthcare sector stakeholders in the UK.

Availability of data and materials: The topic guide used for this qualitative research is available in Additional file 1.BACKGROUND: The independent healthcare sector in the UK collects PROMs for several surgical procedures, but implementation has been challenging. We aimed to understand the enablers and barriers to PROMs implementation in the independent healthcare sector in the UK. METHOD: Between January and May 2021, we remotely conducted semi-structured interviews with hospital consultants, hospital managers and other clinical staff using a topic guide developed from an implementation science framework called the Theoretical Domains Framework (TDF). RESULTS: We interviewed 6 hospital consultants, 5 hospital managers, and 3 other clinical staff (1 nurse and 2 physiotherapists) across 8 hospitals. Common barriers included: the perception that PROMs are predominantly a reporting requirement rather than a quality improvement tool, absence of feedback mechanisms for PROMs data for clinicians, poor awareness of PROMs among healthcare professionals and the public, absence of direction or commitment from leadership, and limited support from hospital consultants. Common enablers included: regular feedback of PROMs data to clinicians, designating roles and responsibilities, formally embedding PROMs collection into patient pathways, and involvement of hospital consultants in developing strategies to improve PROMs uptake. CONCLUSION: To support PROMs implementation, independent hospitals need to develop long-term organisational strategies that involve sustained leadership commitment, goals or targets, training opportunities to staff, and regular feedback of PROMs data at clinical or governance meetings. The primary purpose of PROMs needs to be reframed to independent healthcare sector stakeholders as a quality improvement tool rather than a reporting requirement.Private Healthcare Information Network (PHIN

Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: A case series

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity

High-precision photometric redshifts from Spitzer/IRAC : extreme [3.6] - [4.5] colors identify galaxies in the redshift range z ~ 6.6 - 6.9.

One of the most challenging aspects of studying galaxies in the z 7 universe is the infrequent confirmation of their redshifts through spectroscopy, a phenomenon thought to occur from the increasing opacity of the intergalactic medium to Lyα photons at z \u3e 6.5. The resulting redshift uncertainties inhibit the efficient search for [C II] in z ~ 7 galaxies with sub-millimeter instruments such as ALMA, given their limited scan speed for faint lines. One means by which to improve the precision of the inferred redshifts is to exploit the potential impact of strong nebular emission lines on the colors of z ∼ 4 – 8 galaxies as observed by Spitzer/IRAC. At z ~ 6.8, galaxies exhibit IRAC colors as blue as[3.6] [4.5] 1 - ~- , likely due to the contribution of [O III]+Hβ to the 3.6 μm flux combined with the absence of line contamination in the 4.5 μm band. In this paper we explore the use of extremely blue [3.6] [4.5] - colors to identify galaxies in the narrow redshift window z ~ 6.6 – 6.9. When combined with an I-dropout criterion, we demonstrate that we can plausibly select a relatively clean sample of z ~ 6.8 galaxies. Through a systematic application of this selection technique to our catalogs from all five CANDELS fields, we identify 20 probable z ~ 6.6 – 6.9 galaxies. We estimate that our criteria select the ∼50% strongest line emitters at z ~ 6.8 and from the IRAC colors we estimate a typical [O III]+Hb rest-frame equivalent width of 1085 Å for this sample. The small redshift uncertainties on our sample make it particularly well suited for follow-up studies with facilities such as ALMA

Quantum Size Effect transition in percolating nanocomposite films

We report on unique electronic properties in Fe-SiO2 nanocomposite thin films in the vicinity of the percolation threshold. The electronic transport is dominated by quantum corrections to the metallic conduction of the Infinite Cluster (IC). At low temperature, mesoscopic effects revealed on the conductivity, Hall effect experiments and low frequency electrical noise (random telegraph noise and 1/f noise) strongly support the existence of a temperature-induced Quantum Size Effect (QSE) transition in the metallic conduction path. Below a critical temperature related to the geometrical constriction sizes of the IC, the electronic conductivity is mainly governed by active tunnel conductance across barriers in the metallic network. The high 1/f noise level and the random telegraph noise are consistently explained by random potential modulation of the barriers transmittance due to local Coulomb charges. Our results provide evidence that a lowering of the temperature is somehow equivalent to a decrease of the metal fraction in the vicinity of the percolation limit.Comment: 21 pages, 8 figure

Characterization and applications of a Crimean-Congo hemorrhagic fever virus nucleoprotein-specific Affimer: Inhibitory effects in viral replication and development of colorimetric diagnostic tests

Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera

Accounting for the increasing benefits from scarce ecosystems

Governments are catching up with economic theory and practice by increasingly integrating ecosystem service values into national planning processes, including benefitcost analyses of public policies. Such analyses require information not only about today’s benefits from ecosystem services but also on how benefits change over time. We address a key limitation of existing policy guidance, which assumes that benefits from ecosystem services remain unchanged. We provide a practical rule that is grounded in economic theory and evidence-based as a guideline for how benefits change over time: They rise as societies get richer and even more so when ecosystem services are declining. Our proposal will correct a substantial downward bias in currently used estimates of future ecosystem service values. This will help governments to reflect the importance of ecosystems more accurately in benefit-cost analyses and policy decisions they inform

Bilijarna funkcija u radnika profesionalno izloženih aluminijskoj prašini i dimu

This study investigated billiary secretory function in workers occupationally exposed to aluminium dust and fumes. It included a group of 34 male workers aged (44.1±7.8) years and exposed up to 4.6 mg m-3 of aluminium dust and fumes in workplace air for (21.6±2.5) years, and a group of 30 unexposed control male workers. Serum and urine aluminium levels were measured in both groups before and after chelating treatment with 1 g deferoxamine by intramuscular injection. Billiary function was assessed by measuring gamma-glutamyl transpeptidase, alkaline phosphatase, 5-nucleotidase, cholesterol and its fractions, total and indirect bilirubin, and bile acids. We then analysed the relationship between Al exposure and billiary function. In the exposed group mean serum aluminium was significantly higher [(4.91±3.86) µg L-1] than in controls. The same was true for urine Al before [(1.57±1.93) µg L-1] and after deferoxamine [(11.51±14.97) µg L-1]. Total and indirect bilirubin and alkaline phosphatase were significantly higher in the exposed than in control workers, and they correlated with urine Al after the chelating treatment. Our findings suggest that chronic occupational exposure to aluminium dust and fumes leads to a significant body retention of aluminium. The impaired biliary secretion in the exposed workers manifested itself in subclinical signs of cholestasis.Eksperimentalna istraživanja na životinjama pokazuju da kronična izloženost aluminiju može izazvati smanjen prijenos organskih aniona preko žučnih kanalića, što ima za posljedicu poremećaje sekrecije žuči i kolestazu. Učinci kronične izloženosti aluminiju na bilijarnu funkciju u ljudi do sada nisu istraživani. Procjenjivali smo učinke na bilijarnu funkciju radnika koji su profesionalno izloženi prašini i dimu aluminija. U izloženoj skupini bila su 34 muškarca, životne dobi (44,1±7,8) godina koji su tijekom (21,6±2,5) godina bili izloženi razini do 4,6 mg m-3 prašine i dima aluminija. Kontrolna skupina sastojala se od 30 neizloženih radnika. Vrijednosti aluminija određene su u serumu i mokraći u obje skupine prije i nakon davanja kelatirajućeg spoja (deferoksamin u dozi od 1 g im.). Za procjenu bilijarne funkcije rabljeni su ovi pokazatelji: γ-glutamil transpeptidaza, alkalna fosfataza, 5-nukleozidaza, kolesterol, ukupni i indirektni bilirubin te žučne kiseline. Analizirana je korelacija između izloženosti aluminiju i bilijarne funkcije. Srednja vrijednost Al u serumu izloženih radnika [(4,91±3,86) µg L-1], kao i koncentracije Al u mokraći prije [(1,57±1,93) µg L-1] i nakon primjene kelatirajućeg spoja [(11,5±15,0) µg L-1] bile su statistički značajno više u odnosu na vrijednosti u kontrolnih ispitanika. Vrijednosti ukupnog i indirektnoog bilirubina te alkalne fosfataze bile su statistički značajno više u izloženih radnika i pozitivno su korelirale s ukupnim Al izlučenim mokraćom nakon primjene kelatora. Može se zaključiti da kronična profesionalna izloženost prašini i dimu aluminija dovodi do tjelesnog opterećenja aluminijem i poremećaja bilijarne funkcije, što se odražava supkliničkim znakovima kolestaze

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted