A qualitative evaluation of coproduction of research: ‘If you do it properly, you will get turbulence'

Abstract: Background: Patients and public members are increasingly involved across the different stages of the research process. Their involvement is particularly important in the conception and design of applied health research where it enables people with lived experience to influence the aims, content, focus and methods. Objective: To evaluate the process of coproducing a mental health–related research proposal suitable for funding through a national health research funding body. Methods: Reflections from members of the public (n = 3) and academic researchers (n = 3) were collected through semi‐structured interviews. Data were thematically analysed. Results: Thematic analysis identified five overarching themes: valuing the lived experience perspective; matching ambitions to the funded research process; ‘Us and them’: power, relationships and trust; challenges; and benefits of coproduction. Conclusions: Our findings suggest that for successful coproduction of a research funding application, an open and trusting atmosphere, where equal relationships are established and a shared common goal agreed is essential. Although relationships with research professionals were framed by trust and mutual respect for some public advisors, others felt a sense of ‘us and them’. With various tensions played out through interpersonal conflict, difficult conversations and disagreements, coproduction was not a positive experience for all stakeholders involved. Among the learning was that when collaboration of this kind is constrained by time or funding, genuine, impactful coproduction can be more challenging than is generally acknowledged

Synthesis of Zn(II) and Al(III) complexes of diaminocyclohexane derived ligands and their exploitation for the ring opening polymerization of rac-lactide

Two series of ligands based on diaminocyclohexane (DACH) have been prepared and successfully complexed to Al(III) and Zn(II) metal centres. Solution and solid-state studies reveal a tendency to form mono- or bis-ligated forms depending on the steric bulk of the ligand. These complexes have been tested for their ability to ring open rac-lactide. Al(III) based complexes generally gave atactic PLA after a polymerization time of 1-2 days. The Zn(II) complexes, were found to be more active and furnished PLA with a slight heterotactic bias

Health Is Still Social: Contemporary Examples in the Age of the Genome

Holtz and colleagues argue that social medicine, including an understanding of the social roots of disease, is as important now as it has ever been

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc

SummaryMYC contributes to the pathogenesis of a majority of human cancers, yet strategies to modulate the function of the c-Myc oncoprotein do not exist. Toward this objective, we have targeted MYC transcription by interfering with chromatin-dependent signal transduction to RNA polymerase, specifically by inhibiting the acetyl-lysine recognition domains (bromodomains) of putative coactivator proteins implicated in transcriptional initiation and elongation. Using a selective small-molecule bromodomain inhibitor, JQ1, we identify BET bromodomain proteins as regulatory factors for c-Myc. BET inhibition by JQ1 downregulates MYC transcription, followed by genome-wide downregulation of Myc-dependent target genes. In experimental models of multiple myeloma, a Myc-dependent hematologic malignancy, JQ1 produces a potent antiproliferative effect associated with cell-cycle arrest and cellular senescence. Efficacy of JQ1 in three murine models of multiple myeloma establishes the therapeutic rationale for BET bromodomain inhibition in this disease and other malignancies characterized by pathologic activation of c-Myc.PaperFlic

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.BackgroundPatients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism.MethodsOur objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± sd) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430)ml/24hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4)ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate.ResultsDuring the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I–treated patients and 12 placebo-treated patients died during the 28days after the onset of treatment.ConclusionsrhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity