On the 12th day of Christmas, a statistician sent to me . . .

The BMJ’s statistical editors relish a quiet Christmas, so make their wish come true and pay attention to the list of common statistical faux pas presented here by Riley and colleagues

The Procedural Fairness Limitations of Fitness to Practise Hearings: a case study into social work

The norm in fitness to practise proceedings (FTPP) is that where sanctions might be imposed procedural fairness requires a court-like hearing. This article questions that paradigm, using empirical research to focus on the FTPP to which social workers must account. Procedural fairness is a multi-faceted legitimising concept used to justify the design of decision-making processes. With FTPPs, the major justification is an ‘instrumentally’ focused model of procedural fairness which prioritises making decisions that look right, a goal which is delivered in the context of social work. But other justifications for procedural fairness are inadequately fulfilled, with in particular a ‘dignitarian’ respect not achieved due to the high levels of non-attendance by registrant social workers. Further, procedural fairness as ‘public accountability’ is undermined due to the relative lack of engagement of FTPPs with the perspective of the social work community. These findings hint that in the context of a poorly organised and resource-poor profession other hybrid forms of FTPP might have a stronger claim to procedural fairness than the court-like model

Inverse modelling for predicting both water and nitrate movement in a structured-clay soil (Red Ferrosol)

Soil physical parameter calculation by inverse modelling provides an indirect way of estimating the unsaturated hydraulic properties of soils. However many measurements are needed to provide sufficient data to determine unknown parameters. The objective of this research was to assess the use of unsaturated water flow and solute transport experiments, in horizontal packed soil columns, to estimate the parameters that govern water flow and solute transport. The derived parameters are then used to predict water infiltration and solute migration in a repacked soil wedge. Horizontal columns packed with Red Ferrosol were used in a nitrate diffusion experiment to estimate either three or six parameters of the van Genuchten–Mualem equation while keeping residual and saturated water content, and saturated hydraulic conductivity fixed to independently measured values. These parameters were calculated using the inverse optimisation routines in Hydrus 1D. Nitrate concentrations measured along the horizontal soil columns were used to independently determine the Langmuir adsorption isotherm. The soil hydraulic properties described by the van Genuchten–Mualem equation, and the NO3– adsorption isotherm, were then used to predict water and NO3– distributions from a point-source in two 3D flow scenarios. The use of horizontal columns of repacked soil and inverse modelling to quantify the soil water retention curve was found to be a simple and effective method for determining soil hydraulic properties of Red Ferrosols. These generated parameters supported subsequent testing of interactive flow and reactive transport processes under dynamic flow conditions

Ultrastructural identification of uncoated caveolin-independent early endocytic vehicles

Using quantitative light microscopy and a modified immunoelectron microscopic technique, we have characterized the entry pathway of the cholera toxin binding subunit (CTB) in primary embryonic fibroblasts. CTB trafficking to the Golgi complex was identical in caveolin-1null (Cav1−/−) mouse embryonic fibroblasts (MEFs) and wild-type (WT) MEFs. CTB entry in the Cav1−/− MEFs was predominantly clathrin and dynamin independent but relatively cholesterol dependent. Immunoelectron microscopy was used to quantify budded and surface-connected caveolae and to identify noncaveolar endocytic vehicles. In WT MEFs, a small fraction of the total Cav1-positive structures were shown to bud from the plasma membrane (2% per minute), and budding increased upon okadaic acid or lactosyl ceramide treatment. However, the major carriers involved in initial entry of CTB were identified as uncoated tubular or ring-shaped structures. These carriers contained GPI-anchored proteins and fluid phase markers and represented the major vehicles mediating CTB uptake in both WT and caveolae-null cells

Zero-Release Mixed Waste Process Facility Design and Testing

A zero-release offgas cleaning system for mixed-waste thermal treatment processes has been evaluated through experimental scoping tests and process modeling. The principles can possibly be adapted to a fluidized-bed calcination or stream reforming process, a waste melter, a rotarykiln process, and possibly other waste treatment thermal processes. The basic concept of a zero-release offgas cleaning system is to recycle the bulk of the offgas stream to the thermal treatment process. A slip stream is taken off the offgas recycle to separate and purge benign constituents that may build up in the gas, such as water vapor, argon, nitrogen, and CO2. Contaminants are separated from the slip stream and returned to the thermal unit for eventual destruction or incorporation into the waste immobilization media. In the current study, a standard packed-bed scrubber, followed by gas separation membranes, is proposed for removal of contaminants from the offgas recycle slipstream. The scrub solution is continuously regenerated by cooling and precipitating sulfate, nitrate, and other salts that reach a solubility limit in the scrub solution. Mercury is also separated by the scrubber. A miscible chemical oxidizing agent was shown to effectively oxidize mercury and also NO, thus increasing their removal efficiency. The current study indicates that the proposed process is a viable option for reducing offgas emissions. Consideration of the proposed closed-system offgas cleaning loop is warranted when emissions limits are stringent, or when a reduction in the total gas emissions volume is desired. Although the current closed-loop appears to be technically feasible, economical considerations must be also be evaluated on a case-by-case basis

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile

Discarded livers tested by normothermic machine perfusion in the VITTAL trial:Secondary end points and 5-year outcomes

Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH &gt;7.65 and bicarbonate levels &gt;25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608).</p

Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion

Increased use of high-risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell-based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate-clearing (LC) and non-lactate-clearing (non-LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non-LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow &gt;150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non-LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non-LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high-risk livers.</p

Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial

Background: The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. / Purpose: To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. / Materials and Methods: In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3–5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. / Results: Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). / Conclusion: An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings