Background
Biliary leakage remains a major cause of morbidity after liver resection. Previous prognostic studies of posthepatectomy biliary leakage (PHBL) lacked power, population homogeneity, and ...model validation. The present study aimed to develop a risk score for predicting severe PHBL.
Methods
In this multicentre observational study, patients who underwent liver resection without hepaticojejunostomy in one of nine tertiary centres between 2012 and 2015 were randomly assigned to a development or validation cohort in a 2 : 1 ratio. A model predicting severe PHBL (International Study Group of Liver Surgery grade B/C) was developed and further validated.
Results
A total of 2218 procedures were included. PHBL of any severity and severe PHBL occurred in 141 (6·4 per cent) and 92 (4·1 per cent) patients respectively. In the development cohort (1475 patients), multivariable analysis identified blood loss of at least 500 ml, liver remnant ischaemia time 45 min or more, anatomical resection including segment VIII, transection along the right aspect of the left intersectional plane, and associating liver partition and portal vein ligation for staged hepatectomy as predictors of severe PHBL. A risk score (ranging from 0 to 5) was built using the development cohort (area under the receiver operating characteristic curve (AUROC) 0·79, 95 per cent c.i. 0·74 to 0·85) and tested successfully in the validation cohort (AUROC 0·70, 0·60 to 0·80). A score of at least 3 predicted an increase in severe PHBL (19·4 versus 2·6 per cent in the development cohort, P < 0·001; 15 versus 3·1 per cent in the validation cohort, P < 0·001).
Conclusion
The present risk score reliably predicts severe PHBL. It represents a multi‐institutionally validated prognostic tool that can be used to identify a subset of patients at high risk of severe PHBL after elective hepatectomy.
Multi‐institutionally validated prognostic tool
B vitamins may protect against age-related macular degeneration (AMD). We evaluated the associations of dietary intake and serum vitamins with the incidence of advanced AMD in the Alienor study. The ...Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006–2008). Examinations were performed every two years over an eight-year period. The incidence of AMD is based on retinal fundus photographs and spectral-domain optical coherence tomography examinations. Among the 861 included participants, 93 developed incident AMD during a median follow-up time of 9.8 years. Participants with normal serum folate (≥10 nmol/L) significantly had a 51% reduced risk for AMD in the fully adjusted Cox model (HR, 0.49 95% CI, 0.25–0.95, p = 0.036). Participants with a higher dietary intake of B5 and B6 vitamins had a lower risk for developing AMD of up to 28% (HR, 0.72 for 1-SD increase 0.53–0.99, p = 0.049; HR, 0.90 0.81–0.99, p = 0.049, respectively). This cohort study of older adults suggests a strong association between a normal serum folate status, a high dietary intake of B5 and B6 and a lower risk for developing advanced AMD. Adopting a healthy diet rich in B vitamins may help to reduce vision loss due to AMD.
We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies ...and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε μτ . The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of −0.0041≤ε μτ ≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.
Solar flares convert magnetic energy into thermal and nonthermal plasma energy, the latter implying particle acceleration of charged particles such as protons. Protons are injected out of the coronal ...acceleration region and can interact with dense plasma in the lower solar atmosphere, producing mesons that subsequently decay into gamma rays and neutrinos at O ( MeV − GeV ) energies. We present the results of the first search for GeV neutrinos emitted during solar flares carried out with the IceCube Neutrino Observatory. While the experiment was originally designed to detect neutrinos with energies between 10 GeV and a few PeV, a new approach allowing for a O ( GeV ) energy threshold will be presented. The resulting limits allow us to constrain some of the theoretical estimates of the expected neutrino flux.
Significance
Dopamine and glutamate in the prefrontal cortex are important substrates of higher cognitive functions, which are impaired in neuropsychiatric disorders. As regards glutamatergic ...pathways, a role for the NMDA receptor coagonist
d
-serine has been highlighted, yet its relationship to dopaminergic transmission remains unclear. In this study, we reveal that
d
-serine plays a pivotal role in the modulation by dopamine of NMDA receptor activity and cognitive performance in the prefrontal cortex. Comprehensive evidence for this interaction is provided at the synaptic, neuronal, network, and behavioral levels. These observations are of relevance to the pathophysiology and treatment of cognitive impairment in numerous disorders involving disruption of the frontocortical dialogue between dopamine and glutamate.
Prefrontal control of cognitive functions critically depends upon glutamatergic transmission and N-methyl D-aspartate (NMDA) receptors, the activity of which is regulated by dopamine. Yet whether the NMDA receptor coagonist
d
-serine is implicated in the dopamine–glutamate dialogue in the prefrontal cortex (PFC) and other brain areas remains unexplored. Here, using electrophysiological recordings, we show that
d
-serine is required for the fine-tuning of glutamatergic neurotransmission, neuronal excitability, and synaptic plasticity in the PFC through the actions of dopamine at D
1
and D
3
receptors. Using in vivo microdialysis, we show that D
1
and D
3
receptors exert a respective facilitatory and inhibitory influence on extracellular levels and activity of
d
-serine in the PFC, with actions expressed primarily via the cAMP/protein kinase A (PKA) signaling cascade. Further, using functional magnetic resonance imaging (fMRI) and behavioral assessment, we show that
d
-serine is required for the potentiation of cognition by D
3
R blockade as revealed in a test of novel object recognition memory. Collectively, these results unveil a key role for
d
-serine in the dopaminergic neuromodulation of glutamatergic transmission and PFC activity, findings with clear relevance to the pathogenesis and treatment of diverse brain disorders involving alterations in dopamine–glutamate cross-talk.
Objectives In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was ...devised and its usefulness with older patients assessed.Design Retrospective multicentre cohort study.Setting General and teaching hospitals in Belgium, France, the Netherlands, and Switzerland.Patients 5132 consecutive patients with clinically suspected pulmonary embolism.Intervention Development of a new D-dimer cut-off point in patients aged >50 years in a derivation set (data from two multicentre cohort studies), based on receiver operating characteristics (ROC) curves. This cut-off value was then validated with two independent validation datasets. Main outcome measures The proportion of patients in the validation cohorts with a negative D-dimer test, the proportion in whom pulmonary embolism could be excluded, and the false negative rates.Results The new D-dimer cut-off value was defined as (patient’s age×10) μg/l in patients aged >50. In 1331 patients in the derivation set with an “unlikely” score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (<500 μg/l). In the two validation sets, the increase in the proportion of patients with a D-dimer below the new cut-off value compared with the old value was 5% and 6%. This absolute increase was largest among patients aged >70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets.Conclusions The age adjusted D-dimer cut-off point, combined with clinical probability, greatly increased the proportion of older patients in whom pulmonary embolism could be safely excluded.
Worldwide fisheries generate large volumes of fishery waste and it is often assumed that this additional food is beneficial to populations of marine top-predators. We challenge this concept via a ...detailed study of foraging Cape gannets Morus capensis and of their feeding environment in the Benguela upwelling zone. The natural prey of Cape gannets (pelagic fishes) is depleted and birds now feed extensively on fishery wastes. These are beneficial to non-breeding birds, which show reduced feeding effort and high survival. By contrast, breeding gannets double their diving effort in an attempt to provision their chicks predominantly with high-quality, live pelagic fishes. Owing to a scarcity of this resource, they fail and most chicks die. Our study supports the junk-food hypothesis for Cape gannets since it shows that non-breeding birds can survive when complementing their diet with fishery wastes, but that they struggle to reproduce if live prey is scarce. This is due to the negative impact of low-quality fishery wastes on the growth patterns of gannet chicks. Marine management policies should not assume that fishery waste is generally beneficial to scavenging seabirds and that an abundance of this artificial resource will automatically inflate their populations.
Background: Risk factors for post‐thrombotic syndrome (PTS) remain poorly understood.
Objectives: In this multinational multicenter study, we evaluated whether subtherapeutic warfarin ...anticoagulation was associated with the development of PTS.
Methods: Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 5–7 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation.
Results: Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared with 21.6% in those with an INR below two for ≤ 20% of the time (P = 0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% confidence interval CI 1.10–2.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.13–3.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.14–3.00) crude and 1.88 (95% CI 1.15–3.07) adjusted.
Conclusion: Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS.
Episomes with the NUP214-ABL1 fusion gene have been observed in 6% of T-ALL. In this multicentric study we collected 27 cases of NUP214-ABL1-positive T-ALL. Median age was 15 years with male ...predominance. Outcome was poor in 12 patients. An associated abnormality involving TLX1 or TLX3 was found in all investigated cases. Fluorescent in situ hybridization revealed a heterogeneous pattern of NUP214-ABL1 amplification. Multiple episomes carrying the fusion were detected in 24 patients. Episomes were observed in a significant number of nuclei in 18 cases, but in only 1-5% of nuclei in 6. In addition, intrachromosomal amplification (small hsr) was identified either as the only change or in association with episomes in four cases and two T-ALL cell lines (PEER and ALL-SIL). One case showed insertion of apparently non-amplified NUP214-ABL1 sequences at 14q12. The amplified sequences were analyzed using array-based CGH.These findings confirm that the NUP214-ABL1 gene requires amplification for oncogenicity; it is part of a multistep process of leukemogenesis; and it can be a late event present only in subpopulations. Data also provide in vivo evidence for a model of episome formation, amplification and optional reintegration into the genome. Implications for the use of kinase inhibitors are discussed.
We consider the two-dimensional (2d) Ising model on a infinitely long cylinder and study the probabilities $p_i$ to observe a given spin configuration $i$ along a circular section of the cylinder. ...These probabilities also occur as eigenvalues of reduced density matrices in some Rokhsar-Kivelson wave-functions. We analyze the subleading constant to the R\'enyi entropy $R_n=1/(1-n) \ln (\sum_i p_i^n)$ and discuss its scaling properties at the critical point. Studying three different microscopic realizations, we provide numerical evidence that it is universal and behaves in a step-like fashion as a function of $n$, with a discontinuity at the Shannon point $n=1$. As a consequence, a field theoretical argument based on the replica trick would fail to give the correct value at this point. We nevertheless compute it numerically with high precision. Two other values of the R\'enyi parameter are of special interest: $n=1/2$ and $n=\infty$ are related in a simple way to the Affleck-Ludwig boundary entropies associated to free and fixed boundary conditions respectively.
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