In Vitro Scaffold Construction for a Bio-artificial Liver

The main focus of this investigation is to design a scaffold that will accommodate a growing Bio-Artificial Liver (BAL) with oxygen. The two design objectives are to find the maximum length and the distance between the artificial capillaries of the scaffold to provide adequate oxygen supply above 1.98 x 10-19 g/um3 to prevent hypoxia to the growing liver tissues. By utilizing industrial modeling software, FIDAP and GAMBIT, a model of a single capillary with liver tissue attached directly was constructed to simulate the oxygen delivery by means of diffusion and convection from the capillary wall to the tissue and the uptake by metabolism. From the results obtained, it was concluded that diffusion, not convection of the oxygen flow within the capillary was the dominant process of oxygen transport throughout the tissue. The maximum distance traveled into the tissue with capillary length of 60 ?m was 147 ?m from the capillary at the inlet side of the tissue while diffusion at the outlet tissue was at a modest 108 ?m. These values are unacceptable for the feasible construction of oxygen transport system solely based on diffusion. Thus, this investigation concludes that novel methods of greater complexity are needed to construct a more efficient and economically applicable oxygen delivery system for the mass production of bio-organs

Translating Research Into Practice: Speeding the Adoption of Innovative Health Care Programs

Looks at case studies of four innovative clinical programs to determine key factors influencing the diffusion and adoption of innovations in health care

The first simultaneous pancreas, renal transplant in a patient with HIV in Australia

We report the first case of a simultaneous pancreas and renal transplantation, in Australia, in a 45 year old male with long standing human immunodeficiency virus infection, type 1 diabetes mellitus and diabetic nephropathy requiring haemodialysis. This patient experienced previous virological failure and subsequent resistance to most nucleoside and non-nucleoside reverse transcriptase inhibitors. However, using novel combinations of anti-retroviral agents, along with careful monitoring, successful outcomes were achieved during the peri and post transplantation period, with excellent pancreas and renal graft function at one year

Conceptualisation and psychometric evaluation of positive psychological outcome measures used in adolescents and young adults living with HIV:a mixed scoping and systematic review protocol

Introduction Sub-Saharan Africa bears the greatest burden of HIV. Concomitant mental disorders are common, necessitating the integration of mental healthcare into routine HIV care. Consequently, it is necessary to holistically evaluate the mental health of adolescents and young adults living with HIV (AYALHIV, 10–24 years old) by measuring negative and positive psychological constructs (eg, anxiety and self-acceptance, respectively). There has been a proliferation of positive psychological outcome measures, but the evidence of their psychometric robustness is fragmented. This review, therefore, seeks to (1) identify positive psychological outcomes used in AYALHIV in sub-Saharan Africa and map the constructs onto corresponding measures and (2) critically appraise the psychometrics of the identified outcomes Methods and analysis This mixed review will be done in two parts. First, a scoping review will identify positive psychological outcomes and map them onto corresponding outcome measures. Subsequently, we will systematically evaluate the psychometric properties of the outcomes identified from the scoping review. Independent and blinded reviewers will search articles in PubMed, Scopus, Web of Science, Africa-Wide Information, CINAHL, PsychINFO and Google Scholar from inception through 30 September 2022. Thereafter, separate independent reviewers will screen the retrieved articles. We will apply a narrative synthesis to map the key constructs emerging from the scoping review. For the systematic review, the risk of bias across studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The quality of the psychometric properties will be rated using the COSMIN checklist and qualitatively synthesised using the modified Grading of Recommendations Assessment, Development and Evaluation checklist. Ethics and dissemination No ethical approvals are needed. The mixed-review outputs will collectively inform the development, implementation and evaluation of bespoke interventions for AYALHIV. Review outcomes will be disseminated in a peer-reviewed journal, on social media and through policy briefs

Tests for latent tuberculosis in people with end stage kidney disease: a systematic review

BACKGROUND: The relative diagnostic accuracy of interferon γ release assays (IGRAs; based on ELISA [enzyme-linked immunosorbent assay] or ELISPOT [enzyme-linked immunosorbent spot], ie, the QuantiFERON and T-SPOT.TB tests, respectively) and the tuberculin skin test (TST) for latent tuberculosis (TB) infection in people with end-stage kidney disease is uncertain and national guidelines for their use are inconsistent. STUDY DESIGN: Systematic review. SELECTION CRITERIA FOR STUDIES: Evaluated performance of tests for latent TB with clinical risk-factor assessment. SETTING & POPULATION: People with end-stage kidney disease (chronic kidney disease stage 5 [eGFR <15] or kidney transplant recipients). No limits on setting. INDEX TESTS: ELISA- or ELISPOT-based IGRAs, TST, assays to detect antimycobacterial antibodies, and flow cytometry-based tests. OUTCOMES: Odds of test positivity with clinical risk factor for latent TB, expressed as ORs and relative ORs (RORs). RESULTS: 47 studies (6,828 participants) were included, but only 30 studies (4,546 participants) contained sufficient data to contribute to meta-analysis. Studies were predominately in the dialysis population (23/30; 3,700 participants) in countries with low to moderate TB prevalence (0.0-50.0 cases/10(5) persons). BCG vaccination rate was variable (2.7%-100.0%). 9 studies compared IGRAs with the TST directly, 17 studies evaluated the TST only, and the other 4 studies evaluated other tests. Compared to a positive TST result, a positive ELISA-based IGRA result was associated more strongly with radiologic evidence of past TB (ROR, 4.29; 95% CI, 1.83-10.3; P = 0.001) and contact with active TB (ROR, 3.36; 95% CI, 1.61-7.01; P = 0.001). Compared to a negative TST result, a negative ELISA-based IGRA result was associated more strongly with BCG vaccination (ROR, 0.30; 95% CI, 0.14-0.63; P = 0.002). There were insufficient data to compare performance of the ELISPOT-based IGRA with the TST or ELISA-based IGRA. LIMITATIONS: 17 of 47 included studies (36.2%) did not contain sufficient data to contribute to meta-analysis. CONCLUSIONS: Compared to the TST, the ELISA-based IGRA was associated more strongly with risk factors for latent TB in end-stage kidney disease

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

“Be patient, dear mother … wait for me”: the neo-infirmity film, female illness and contemporary cinema

In social reality, illness and death occur in myriad ways, yet Hollywood films have historically preferred spectacular, violent death over realist depictions of the terminal stages of life. Yet an ever-growing number of popular films, which I term neo-infirmity films, incorporate episodes of women characters debilitated by illness or injury. Operating at the intersection of melodrama and realism, the scenes are instrumental in staging contemporary cinema's gender politics. I argue that women's deathbed and hospital-bed scenes in contemporary cinema validate anew the maternal role and the figure of the mother, transporting the woman-centered discursive space of melodrama into narrative terrain often hostile to women's presence. Through this relocation, the films emphasize her importance to sons in particular (and less often to daughters, husbands, and the larger family unit). Many such scenes simultaneously undermine women's agency, reducing mothers to principally symbolic, literally immobile roles. Ailing women can become catalysts for male psychological transformation occurring through grief, action, or both in combination. In all, such scenes speak to continued ambivalence surrounding women's representation in popular cinema, and to continued patrolling of the boundaries of female power. This essay compares selected texts from contemporary Hollywood cinema, alongside three parallel discourses that also deploy melodramatic modes of articulation: nonfiction amateur video as relayed via television news programs, international art cinema, and US independent cinema. Arguing for homologies across multiple fields of textual production, I seek through this comparison to generate insights into the cultural work done by filmic representation

Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report.

Based on the profile of genetic alterations occurring in tumor samples from selected diffuse large B-cell lymphoma (DLBCL) patients, 2 recent whole-exome sequencing studies proposed partially overlapping classification systems. Using clustering techniques applied to targeted sequencing data derived from a large unselected population-based patient cohort with full clinical follow-up (n = 928), we investigated whether molecular subtypes can be robustly identified using methods potentially applicable in routine clinical practice. DNA extracted from DLBCL tumors diagnosed in patients residing in a catchment population of ∼4 million (14 centers) were sequenced with a targeted 293-gene hematological-malignancy panel. Bernoulli mixture-model clustering was applied and the resulting subtypes analyzed in relation to their clinical characteristics and outcomes. Five molecular subtypes were resolved, termed MYD88, BCL2, SOCS1/SGK1, TET2/SGK1, and NOTCH2, along with an unclassified group. The subtypes characterized by genetic alterations of BCL2, NOTCH2, and MYD88 recapitulated recent studies showing good, intermediate, and poor prognosis, respectively. The SOCS1/SGK1 subtype showed biological overlap with primary mediastinal B-cell lymphoma and conferred excellent prognosis. Although not identified as a distinct cluster, NOTCH1 mutation was associated with poor prognosis. The impact of TP53 mutation varied with genomic subtypes, conferring no effect in the NOTCH2 subtype and poor prognosis in the MYD88 subtype. Our findings confirm the existence of molecular subtypes of DLBCL, providing evidence that genomic tests have prognostic significance in non-selected DLBCL patients. The identification of both good and poor risk subtypes in patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) clearly show the clinical value of the approach, confirming the need for a consensus classification.Bloodwise (grant number 15037) funded the majority of this study. Genetic sequencing was funded by 14M Genomics, a start-up company that ceased trading February 2016. DJH was funded by a clinician scientist fellowship from the MRC and receives core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. Some of the analysis in this study was performed on the “Viking” high performance computing cluster at the University of York.1

Interim analysis:Open-label extension study of leniolisib for patients with APDS

Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is an inborn error of immunity caused by PI3Kδ hyperactivity. Resultant immune deficiency and dysregulation lead to recurrent sinopulmonary infections, herpes viremia, autoimmunity, and lymphoproliferation. Objective: Leniolisib, a selective PI3Kδ inhibitor, demonstrated favorable impact on immune cell subsets and lymphoproliferation over placebo in patients with APDS over 12 weeks. Here, we report results from an interim analysis of an ongoing open-label, single-arm extension study. Methods: Patients with APDS aged 12 years or older who completed NCT02435173 or had previous exposure to PI3Kδ inhibitors were eligible. The primary end point was safety, assessed via investigator-reported adverse events (AEs) and clinical/laboratory evaluations. Secondary and exploratory end points included health-related quality of life, inflammatory markers, frequency of infections, and lymphoproliferation. Results: Between September 2016 and August 2021, 37 patients (median age, 20 years; 42.3% female) were enrolled. Of these 37 patients, 26, 9, and 2 patients had previously received leniolisib, placebo, or other PI3Kδ inhibitors, respectively. At the data cutoff date (December 13, 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE. Most AEs were grades 1 to 3; none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined as unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (P =.004), and reductions in immunoglobulin replacement therapy occurred in 10 of 27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias, and normalized lymphocyte subsets. Conclusions: Leniolisib was well tolerated and maintained durable outcomes with up to 5 years of exposure in 37 patients with APDS. ClinicalTrials.gov identifier: NCT02859727.</p