Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post- transplant serum creatinine when compared to “Gold Standard” clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future

Constraining meanings with contextuality

In this paper, we defend two claims. First, we argue that a notion of contextuality that has been formalized in physics and psychology is applicable to linguistic contexts. Second, we propose that this formal apparatus is philosophically significant for the epistemology of language because it imposes homogeneous rational constraints on speakers. We propose a Contextuality Principle that explains and articulates these two claims. This principle states that speakers update contextual information by significantly reducing the space of probabilities and variables in a non-commutative way. Some contexts affect other contexts not merely in terms of the information they contain, but also on the basis of their sequential order. In particular, we argue that the Contextuality by Default (CBD) theory provides a formalism that helps explain the role of contextuality in rational linguistic exchanges

Beating the channel capacity limit for linear photonic superdense coding

Dense coding is arguably the protocol that launched the field of quantum communication. Today, however, more than a decade after its initial experimental realization, the channel capacity remains fundamentally limited as conceived for photons using linear elements. Bob can only send to Alice three of four potential messages owing to the impossibility of carrying out the deterministic discrimination of all four Bell states with linear optics, reducing the attainable channel capacity from 2 to log_2 3 \approx 1.585 bits. However, entanglement in an extra degree of freedom enables the complete and deterministic discrimination of all Bell states. Using pairs of photons simultaneously entangled in spin and orbital angular momentum, we demonstrate the quantum advantage of the ancillary entanglement. In particular, we describe a dense-coding experiment with the largest reported channel capacity and, to our knowledge, the first to break the conventional linear-optics threshold. Our encoding is suited for quantum communication without alignment and satellite communication.Comment: Letter: 6 pages, 4 figures. Supplementary Information: 4 pages, 1 figur

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Characterization of Posa and Posa-like virus genomes in fecal samples from humans, pigs, rats, and bats collected from a single location in Vietnam.

Porcine stool-associated RNA virus (posavirus), and Human stool-associated RNA virus (husavirus) are viruses in the order Picornavirales recently described in porcine and human fecal samples. The tentative group (Posa and Posa-like viruses: PPLVs) also includes fish stool-associated RNA virus (fisavirus) as well as members detected in insects (Drosophila subobscura and Anopheles sinensis) and parasites (Ascaris suum). As part of an agnostic deep sequencing survey of animal and human viruses in Vietnam, we detected three husaviruses in human fecal samples, two of which share 97-98% amino acid identity to Dutch husavirus strains and one highly divergent husavirus with only 25% amino acid identity to known husaviruses. In addition, the current study found forty-seven complete posavirus genomes from pigs, ten novel rat stool-associated RNA virus genomes (tentatively named rasavirus), and sixteen novel bat stool-associated RNA virus genomes (tentatively named basavirus). The five expected Picornavirales protein domains (helicase, 3C-protease, RNA-dependent RNA polymerase, and two Picornavirus capsid domain) were found to be encoded by all PPLV genomes. In addition, a nucleotide composition analysis revealed that the PPLVs shared compositional properties with arthropod viruses and predicted non-mammalian hosts for all PPLV lineages. The study adds seventy-six genomes to the twenty-nine PPLV genomes currently available and greatly extends our sequence knowledge of this group of viruses within the Picornavirales order

Are Interaction-free Measurements Interaction Free?

In 1993 Elitzur and Vaidman introduced the concept of interaction-free measurements which allowed finding objects without ``touching'' them. In the proposed method, since the objects were not touched even by photons, thus, the interaction-free measurements can be called as ``seeing in the dark''. Since then several experiments have been successfully performed and various modifications were suggested. Recently, however, the validity of the term ``interaction-free'' has been questioned. The criticism of the name is briefly reviewed and the meaning of the interaction-free measurements is clarified.Comment: 11 pages, 3 eps figures. Contribution to the ICQO 2000, Raubichi, Belaru

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Transport Through Andreev Bound States in a Graphene Quantum Dot

Andreev reflection-where an electron in a normal metal backscatters off a superconductor into a hole-forms the basis of low energy transport through superconducting junctions. Andreev reflection in confined regions gives rise to discrete Andreev bound states (ABS), which can carry a supercurrent and have recently been proposed as the basis of qubits [1-3]. Although signatures of Andreev reflection and bound states in conductance have been widely reported [4], it has been difficult to directly probe individual ABS. Here, we report transport measurements of sharp, gate-tunable ABS formed in a superconductor-quantum dot (QD)-normal system, which incorporates graphene. The QD exists in the graphene under the superconducting contact, due to a work-function mismatch [5, 6]. The ABS form when the discrete QD levels are proximity coupled to the superconducting contact. Due to the low density of states of graphene and the sensitivity of the QD levels to an applied gate voltage, the ABS spectra are narrow, can be tuned to zero energy via gate voltage, and show a striking pattern in transport measurements.Comment: 25 Pages, included SO

Rethinking entrenched narratives about protected areas and human wellbeing in the Global South

Attempts to link human development and biodiversity conservation goals remain a constant feature of policy and practice related to protected areas (PAs). Underlying these approaches are narratives that simplify assumptions, shaping how interventions are designed and implemented. We examine evidence for five key narratives: 1) conservation is pro-poor; 2) poverty reduction benefits conservation; 3) compensation neutralises costs of conservation; 4) local participation is good for conservation; 5) secure tenure rights for local communities support effective conservation. Through a mixed-method synthesis combining a review of 100 peer-reviewed papers and 25 expert interviews, we examined if and how each narrative is supported or countered by the evidence. The first three narratives are particularly problematic. PAs can reduce material poverty, but exclusion brings substantial local costs to wellbeing, often felt by the poorest. Poverty reduction will not inevitably deliver on conservation goals and trade-offs are common. Compensation (for damage due to human wildlife conflict, or for opportunity costs), is rarely sufficient or commensurate with costs to wellbeing and experienced injustices. There is more support for narratives 4 and 5 on participation and secure tenure rights, highlighting the importance of redistributing power towards Indigenous Peoples and Local Communities in successful conservation. In light of the proposed expansion of PAs under the post-2020 Global Biodiversity Framework, we outline implications of our review for the enhancement and implementation of global targets in order to proactively integrate social equity into conservation and the accountability of conservation actors