The kinetic estimated glomerular filtration rate ratio predicts acute kidney injury.

AIM: Kinetic estimated Glomerular Filtration Rate (KeGFR) approximates GFR under non-steady-state conditions. We investigated whether the ratio of KeGFR difference to baseline eGFR could predict acute kidney injury (AKI) earlier than a creatinine-based algorithm that triggered an AKI electronic Alert (eAlert). METHODS: This retrospective, single-centre, proof-of-concept cohort study assessed all patients diagnosed with AKI by an automated serum creatinine-based eAlert. The kinetic eGFR, the kinetic eGFR difference from baseline and the ratio of difference to baseline was calculated in subjects with at least two serum creatinine (sCr) measurements within 72 h of AKI. RESULTS: Patients in the AKI cohort (n = 140) had a significant decline in KeGFR ratio (AKI: 17% IQR 7% to 29%, Non-AKI: 0 IQR -12% to 9%; P-value <.0001). A decrease of the ratio greater than 10% predicted AKI with a sensitivity of 66%, a specificity of 77%, a positive predictive value of 63%, and negative predictive value of 80%. The median lead time between KeGFR ratio decrease and AKI was 24 h (IQR: 19-27 h). CONCLUSIONS: KeGFR ratio is a cheap, simple method that predicted AKI 24 h before laboratory detection. KeGFR may facilitate triaging patients to increased monitoring or intervention.

Targeting interventions for HIV testing and treatment uptake: An attitudinal and behavioural segmentation of men aged 20-34 in KwaZulu-Natal and Mpumalanga, South Africa.

Despite recent improvements, men still have worse HIV outcomes than women in South Africa. This study describes how young men form distinct behavioural and attitudinal subgroups, and is intended to inform the design of targeted interventions to encourage HIV testing and initiation on antiretroviral therapy. Data were collected using a cross-sectional survey with questions on men's attitudes, beliefs and behaviours around HIV/AIDS. A total of 2,019 men were randomly sampled from eight district municipalities in KwaZulu-Natal and Mpumalanga provinces between October 2018 and January 2019. Men were eligible to participate if they were aged 20-34, Black African, had an education level below university graduation, were aware of HIV and were willing to disclose whether they had tested for HIV. Each participant responded to a questionnaire asking about their demographic characteristics, reported sexual behaviour, engagement with HIV testing and treatment services, alcohol consumption, HIV knowledge, attitudes to gender equity and reported level of depressive symptoms. Data were analysed using canonical correlation, hierarchical clustering and factor analysis techniques to produce five groups of men. The results were synthesised using Human Centred Design principles to suggests areas for potential intervention for each segment. The results showed that men vary based on their attitudes to gender and masculinity, use of alcohol, testing and treatment behaviour, HIV-related fears and preferences for testing modalities. Segment 1 (21%) avoids the topic of HIV, perhaps fearful of the impact on his life. Segment 2 (23%) is well connected to his community and has social concerns about HIV. Segment 3 (15%) struggles with more distal determinants of HIV acquisition such as unemployment and poor mental health. Segment 4 (25%) has concerns about the lifestyle changes that would be required if he were HIV positive. Segment 5 (16%) has a strong traditional mindset and is fearful of the ramifications of HIV in his community. The results will be used to design targeted interventions to increase HIV testing and treatment rates among young men in South Africa. Further research is required to understand the impact of interventions designed in this way.

The regulatory utilization of genetic redundancy through responsive backup circuits.

Functional redundancies, generated by gene duplications, are highly widespread throughout all known genomes. One consequence of these redundancies is a tremendous increase to the robustness of organisms to mutations and other stresses. Yet, this very robustness also renders redundancy evolutionarily unstable, and it is, thus, predicted to have only a transient lifetime. In contrast, numerous reports describe instances of functional overlaps that have been conserved throughout extended evolutionary periods. More interestingly, many such backed-up genes were shown to be transcriptionally responsive to the intactness of their redundant partner and are up-regulated if the latter is mutationally inactivated. By manual inspection of the literature, we have compiled a list of such "responsive backup circuits" in a diverse list of species. Reviewing these responsive backup circuits, we extract recurring principles characterizing their regulation. We then apply modeling approaches to explore further their dynamic properties. Our results demonstrate that responsive backup circuits may function as ideal devices for filtering nongenetic noise from transcriptional pathways and obtaining regulatory precision. We thus challenge the view that such redundancies are simply leftovers of ancient duplications and suggest they are an additional component to the sophisticated machinery of cellular regulation. In this respect, we suggest that compensation for gene loss is merely a side effect of sophisticated design principles using functional redundancy.

Measurement and analysis of non-Fickian dispersion in heterogeneous porous media.

Contaminant breakthrough behavior in a variety of heterogeneous porous media was measured in laboratory experiments, and evaluated in terms of both the classical advection-dispersion equation (ADE) and the continuous time random walk (CTRW) framework. Heterogeneity can give rise to non-Fickian transport patterns, which are distinguished by "anomalous" early arrival and late time tails in breakthrough curves. Experiments were conducted in two mid-scale laboratory flow cells packed with clean, sieved sand of specified grain sizes. Three sets of experiments were performed, using a "homogeneous" packing, a randomly heterogeneous packing using sand of two grain sizes, and an exponentially correlated structure using sand of three grain sizes. Concentrations of sodium chloride tracer were monitored at the inflow reservoir and measured at the outflow reservoir. Breakthrough curves were then analyzed by comparison to fitted solutions from the ADE and CTRW formulations. In all three systems, including the "homogeneous" one, subtle yet measurable differences between Fickian and non-Fickian transport were observed. Quantitative analysis demonstrated that the CTRW theory characterized the full shape of the breakthrough curves far more effectively than the ADE.