Ligand-engineered bandgap stability in mixed-halide perovskite LEDs.

Lead halide perovskites are promising semiconductors for light-emitting applications because they exhibit bright, bandgap-tunable luminescence with high colour purity1,2. Photoluminescence quantum yields close to unity have been achieved for perovskite nanocrystals across a broad range of emission colours, and light-emitting diodes with external quantum efficiencies exceeding 20 per cent-approaching those of commercial organic light-emitting diodes-have been demonstrated in both the infrared and the green emission channels1,3,4. However, owing to the formation of lower-bandgap iodide-rich domains, efficient and colour-stable red electroluminescence from mixed-halide perovskites has not yet been realized5,6. Here we report the treatment of mixed-halide perovskite nanocrystals with multidentate ligands to suppress halide segregation under electroluminescent operation. We demonstrate colour-stable, red emission centred at 620 nanometres, with an electroluminescence external quantum efficiency of 20.3 per cent. We show that a key function of the ligand treatment is to 'clean' the nanocrystal surface through the removal of lead atoms. Density functional theory calculations reveal that the binding between the ligands and the nanocrystal surface suppresses the formation of iodine Frenkel defects, which in turn inhibits halide segregation. Our work exemplifies how the functionality of metal halide perovskites is extremely sensitive to the nature of the (nano)crystalline surface and presents a route through which to control the formation and migration of surface defects. This is critical to achieve bandgap stability for light emission and could also have a broader impact on other optoelectronic applications-such as photovoltaics-for which bandgap stability is required.

Disruption of IFNγ, GZMB, PRF1, or LYST Results in Reduced Suppressive Function in Human CD8+ T Cells.

An imbalance between proinflammatory and regulatory processes underlies autoimmune disease pathogenesis. We have shown that acute relapses of multiple sclerosis are characterized by a deficit in the immune suppressive ability of CD8+ T cells. These cells play an important immune regulatory role, mediated in part through cytotoxicity (perforin [PRF]/granzyme [GZM]) and IFNγ secretion. In this study, we further investigated the importance of IFNγ-, GZMB-, PRF1-, and LYST-associated pathways in CD8+ T cell-mediated suppression. Using the CRISPR-Cas9 ribonucleoprotein transfection system, we first optimized efficient gene knockout while maintaining high viability in primary bulk human CD8+ T cells. Knockout was confirmed through quantitative real-time PCR assays in all cases, combined with flow cytometry where appropriate, as well as confirmation of insertions and/or deletions at genomic target sites. We observed that the knockout of IFNγ, GZMB, PRF1, or LYST, but not the knockout of IL4 or IL5, resulted in significantly diminished in vitro suppressive ability in these cells. Collectively, these results reveal a pivotal role for these pathways in CD8+ T cell-mediated immune suppression and provide important insights into the biology of human CD8+ T cell-mediated suppression that could be targeted for immunotherapeutic intervention.

Long-term ex situ normothermic machine perfusion allows regeneration of human livers with severe bile duct injury.

Bile duct regeneration is hypothesized to prevent biliary strictures, a leading cause of morbidity after liver transplantation. Assessing the capacity for biliary regeneration may identify grafts as suitable for transplantation that are currently declined, but this has been unfeasible until now. This study used long-term ex situ normothermic machine perfusion (LT-NMP) to assess biliary regeneration. Human livers that were declined for transplantation were perfused at 36 °C for up to 13.5 days. Bile duct biopsies, bile, and perfusate were collected throughout perfusion, which were examined for features of injury and regeneration. Biliary regeneration was defined as new Ki-67-positive biliary epithelium following severe injury. Ten livers were perfused for a median duration of 7.5 days. Severe bile duct injury occurred in all grafts, and biliary regeneration occurred in 70% of grafts. Traditional biomarkers of biliary viability such as bile glucose improved during perfusion but this was not associated with biliary regeneration (P > .05). In contrast, the maintenance of interleukin-6 and vascular endothelial growth factor-A levels in bile was associated with biliary regeneration (P = .017 for both cytokines). This is the first study to demonstrate biliary regeneration during LT-NMP and identify a cytokine signature in bile as a novel biomarker for biliary regeneration during LT-NMP.

Incidence, epidemiology, and outcomes of acute allograft rejection following liver transplantation in Australia.

Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology, and outcomes of acute rejection have not been well described in Australia. We retrospectively studied consecutive adults who underwent deceased donor LT at a single center between 2010 and 2020. Donor and recipient data at the time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed, and only a graft's first instance of biopsy-proven acute rejection was analyzed. During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p =0.11). The median time to the first episode of rejection was 71 days after LT: 2.2% hyperacute, 50.4% early (≤90 d), and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI: 0.97-1.00, p =0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI: 1.27-5.09, p <0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI: 0.08-0.58, p <0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI: 2.21-4.42, p <0.001) and patient survival (aHR 3.42, 95% CI: 2.35-4.98, p <0.001). In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant, while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors.

Mortality benefit with AF ablation: Impact of normal sinus rhythm seen in CABANA and EAST AFnet.

Atrial fibrillation (AF) is significantly associated with morbidity and mortality and erodes the quality and quantity of life. It is standard of care to treat patients with AF and an increased risk of stroke with oral anticoagulation therapy, but the more daunting question many clinicians face is whether to pursue a "rate-only" or "rhythm" control strategy. Historical studies over the years have sought to answer this question but have found no significant difference in major clinical outcomes between the two strategies. There are opportunities based on new data to improve the natural history of the disease. The EAST AFnet trial for the first time revealed a significant morbidity and mortality advantage to rhythm control therapy when performed early in the disease process of AF and in the setting of comprehensive medical management that was maintained. The CABANA trial clearly demonstrated that catheter ablation was a more effective long-term treatment of AF in general and significantly lowers risk of AF progression compared to medical therapy. Like multiple prior trials of rhythm management strategies, when rhythm control was effective in these trials, independent of therapy assignment, there was a significantly lower risk of adverse outcomes and death. These contemporary data provide optimism that the pervasive mortality risk in patients with AF observed over the past 50 years may be improved by the timing, use, and efficacy of use of therapeutic interventions.

Impact of Share 35 liver transplantation allocation in Australia and New Zealand.

Patients with high model for end-stage liver disease (MELD) scores waiting for liver transplantation in Australia and New Zealand (ANZ) have had limited access to deceased donor livers and therefore binational sharing of livers, for patients with a MELD score ≥35 was introduced in February 2016. Waiting list mortality, post-transplant outcomes and intention-to-treat survival were compared between patients whose MELD score reached 35 on the waiting list between October 2013 and April 2015 (Pre-Share 35 group, n = 23) and patients who were Share 35 listed between February 2016 and May 2022 (Share 35 group, n = 112). There was significantly reduced waiting list mortality in share 35 listed patients in comparison to the pre-Share 35 group (11.7% vs. 52.2%, OR .120 95% CI .044-.328, P < .001). Post-transplant patient and graft survival were not significantly different between the groups (5-year patient survival 82% vs. 84%, P = .991, 5-year graft survival 82% vs. 76%, P = .543). Intention-to-treat survival was superior in the Share 35 group (HR .302, 95% CI .149-.614, P < .001). Introduction of Share 35 in ANZ resulted in a 78% risk reduction in waiting list mortality, equivalent post-transplant survival and an improvement in intention-to-treat survival.

Low rate of surgical site infections after liver transplantation: A 5-year retrospective cohort study.

BACKGROUND: Surgical site infection (SSI) after liver transplant (LT) is common, but no studies have been conducted in Australia. The purpose of this study was to determine the proportion of patients who developed an SSI post-LT in Australia's largest LT unit. METHODS: This was a single-center retrospective cohort study. We included all LT recipients who were aged 18 years or more and received their transplant between March 1, 2018 and April 1, 2023. The primary outcome was to determine the proportion of LT recipients who developed an SSI within 30 days of transplantation. RESULTS: There were 404 LTs performed during the study period, and 375 met inclusion criteria. Of these, 8% (n = 31/375) developed an SSI and were classified as superficial (3%, n = 12/375) or deep/organ space (5%, n = 19/375). The most common antibiotics used for prophylaxis were amoxicillin/clavulanate (75%, n = 281/375), followed by piperacillin/tazobactam (17%, n = 62/375). Independent risk factors associated with the development of SSI were Roux-en-Y hepaticojejunostomy (aOR 3.16, 95% CI 1.17-8.28, p = .02), operative time (per 60-min increment) (aOR 1.23, 95% CI 1.02-1.48), and re-operation (aOR 4.16, 95% CI 1.81-9.58, p < .01). Type of antibiotic received perioperatively was not significantly associated with SSI. CONCLUSION: SSI occurred in 8% of LT recipients and was predominantly related to operation-related factors rather than patient- or antibiotic-related factors.

Hypothermic Oxygenated machine PErfusion for high-risk liver grafts for transplantation: A systematic review and meta-analysis.

BACKGROUND: Hypothermic Oxygenated machine PErfusion (HOPE) can reduce ischemic reperfusion injury and improve outcomes for liver transplant recipients. However, the effect of HOPE on high-risk extended criteria donor (ECD) and donation after circulatory death determination (DCDD) grafts is incomplete, despite the expectation that this cohort benefit maximally from HOPE. Accordingly, this paper aims to characterize the effect of HOPE on ECD and DCDD grafts. METHODS: This study includes all papers comparing HOPE to static cold storage for high-risk ECD and DCDD grafts. Systematic searches of Medline, Embase, and Scopus were completed using the terms "HOPE" OR "hypothermic oxygenated machine perfusion" AND "liver transplantation". Data were extracted and analyzed using IBM SPSS to perform the meta-analysis. RESULTS: A total of 2286 records were identified, with 10 meeting the inclusion criteria. Overall, the quality of evidence is heterogenous with many papers relying on retrospective controls. However, pooled analysis demonstrates HOPE to significantly reduce the rate of early allograft dysfunction, 12-month graft failure, re-transplantation, total biliary complications, and non-anastomotic strictures for high-risk grafts. CONCLUSIONS: There is good evidence that HOPE improves outcomes following liver transplantation across a number of biochemical and clinical endpoints for high-risk grafts. Of note, the reduction in biliary complications and re-transplantation is particularly significant given the morbidity associated with these endpoints. However, further, high-quality prospective trials with contemporary controls and clinically relevant primary endpoints are needed to better define the impact of HOPE for this cohort of grafts.

Incorporating a hemodialysis filter into a commercial normothermic perfusion system to facilitate long-term preservation of human split-livers.

BACKGROUND: Normothermic machine perfusion (NMP) allows for the assessment and resuscitation of ex-vivo human livers prior to transplantation. Commercially available NMP systems are closed circuits that accumulate metabolic waste and cytokines over time, potentially limiting organ preservation times. Dialysis has been proposed as a method to remove waste and excess fluid from such systems. This study aimed to demonstrate the utility of integrating dialysis into a commercially available system by quantifying solute removal. METHODS: A dialysis filter was attached in parallel to a commercially available liver perfusion system. Three livers declined for transplantation were split before undergoing long-term NMP with blood using the modified system. During perfusion, dialysate flow rates were set in the range of 100-600 mL/h for short periods of time. At each flow rate, perfusate and spent dialysate samples were collected and analyzed for solute clearance. RESULTS: The addition of dialysis to a commercial NMP system removed water-soluble waste and helped regulate electrolyte concentrations. Interleukin-6 was successfully removed from the perfusate. Solute clearance was proportional to dialysate flow rate. A guide for our perfusion setup was created for the appropriate selection of dialysis flow rates and duration based on real-time perfusate composition. CONCLUSIONS: Dialysis circuits can efficiently remove waste and regulate perfusate composition, and can be easily incorporated to improve the performance of commercially available systems. Quantification of the effect of dialysis on perfusate composition enables refined dialysis control to optimize electrolyte profiles and avoid the over- or under-correction of key solutes.

Indocyanine green: A novel marker for assessment of graft quality during ex situ normothermic machine perfusion of human livers.

BACKGROUND: Ex situ machine perfusion facilitates the assessment of livers prior to transplantation. However, currently available markers of liver function poorly predict long-term graft function. Indocyanine green (ICG) is a liver-specific dye which, although common in vivo, has never been comprehensively evaluated for the assessment of graft quality during ex situ machine perfusion. This study aimed to assess the utility of ICG in the ex situ setting. METHODS: Using a customized long-term perfusion system, human livers that were not suitable for transplantation were perfused using a red cell-based perfusate. ICG was delivered into the perfusate on days 0, 1, and 4 to assess ICG clearance (spectrophotometric absorbance at 805 nm) and ICG fluorescence (near-infrared camera). RESULTS: Sixteen partial livers were perfused for a median duration of 172 h (7.2 days). On day 0, the median ICG perfusate disappearance rate (PDR) was 7.5%/min and the median ICG retention at 15 min was 9.9%. Grafts that survived ≥7 days had a significantly higher median ICG PDR on day 0 (14.5%/min vs. 6.5%/min, p = 0.005) but not on days 1 or 4. ICG perfusion demonstrated that long-surviving grafts had a significantly lower median red-value (89.8 vs. 118.6, p = 0.011) and a significantly lower median blue-value (12.9 vs. 22.6, p = 0.045) than short-surviving grafts. CONCLUSION: ICG is a novel marker for the assessment of liver function during ex situ normothermic machine perfusion. ICG PDR and quantitative ICG perfusion can distinguish between long- and short-surviving grafts and demonstrate the utility of ICG in the assessment of graft quality prior to transplant.

The POWER-PAK Score Characterizes Tumor Response to 3 Months of Preoperative Endocrine Therapy.

BACKGROUND: The Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions (POWER, NCT04272801) trial aims to determine whether 3 months of preoperative endocrine therapy (pre-ET) informs adjuvant radiation therapy decisions among older women with early stage, ER-positive breast cancer. We propose the POWER Pathologic Assessment and Ki-67 (POWER-PAK) scoring system to characterize the histologic effects of pre-ET. METHODS: Histologic evaluation was performed on core biopsy and lumpectomy specimens from 37 POWER trial participants who completed pre-ET and surgery. The POWER-PAK score consists of tumor regression, decrease in Ki-67 expression, and ER expression, each ranging from 0 to 2. Scores were aggregated to create the POWER-PAK score with a range from 0 to 6. Participants with no residual tumor were labelled 6-NRT. RESULTS: ER expression did not decrease after pre-ET. Ki-67 decreased from 13% in biopsy specimens to 5% in the lumpectomy specimens (p < 0.001). Cellularity decreased from 40% to 23% (p < 0.001). There was heterogeneity of POWER-PAK scores ranging from 2 to 6-NRT: score of 2, n = 2 (5.4%); 4, n = 8 (21.6%); 5, n = 4 (10.8%); 6, n = 16 (43.2%); and 6-NRT, n = 7 (18.9%). Participants with a score ≥ 5 were more likely to have smaller tumors after pre-ET compared with those with a score < 5 (p = 0.04). CONCLUSIONS: The tumor responses following treatment with pre-ET are heterogenous. We propose that the POWER-PAK scoring system can be used to quantify response to pre-ET. Future studies will explore the use of POWER-PAK to support informed decision-making for adjuvant therapy options for older women with early stage breast cancer.

Safety of laparoscopic repair of incisional hernias in liver transplant recipients.

INTRODUCTION: Incisional hernia is a common complication following liver transplantation occurring in 5%-34% of patients. Traditionally, open repair was standard due to fear of abdominal adhesions, postoperative complications and lack of experience with laparoscopic techniques. Laparoscopic incisional hernia repair (LIHR) has now become routine in non-transplant patients, with improved postoperative outcomes. In this study, we compared outcomes after laparoscopic and open incisional hernia repair after liver transplantation at a high-volume liver transplant center. METHODS: We performed a retrospective cohort study including all incisional hernia repairs performed on post-liver transplant patients at a major liver transplant center in Australia from 2010 to 2021. Donor, recipient, intraoperative and postoperative variables were collected from the electronic medical record focusing on laparoscopic and open repairs. RESULTS: Between January 2010 and March 2021, 138 patients underwent incisional hernia repair: 40 laparoscopic (29%) and 98 open (71%). No difference in wound infection (2.5% vs. 7.7%, p = .243); wound dehiscence (.00% vs. 2.3%, p = .332) or hernia recurrence (16.3% vs. 23.0%, p = .352) was seen between treatment groups. For larger incisional hernias (>5 cm) we found that a laparoscopic repair reduced length of stay compared to open-repair (3.89 vs. 4.57 days, p = .026). CONCLUSION: Laparoscopic repair of larger incisional hernias reduced postoperative length of hospital stay, whilst potential advantages may include reduced wound complications and hernia recurrence. Importantly, laparoscopic repair did not increase postoperative complication rates and represents a safe technique for repair in this demographic.

Laparoscopic donor nephrectomy-Technique and peri-operative outcomes in an Australian transplant center.

INTRODUCTION: Demand for donor kidneys far exceeds the availability of organs from deceased donors. Living donor kidneys are an important part of addressing this shortfall, and laparoscopic nephrectomy is an important strategy to reduce donor morbidity and increase the acceptability of living donation. AIM: To retrospectively review the intraoperative and postoperative safety, technique, and outcomes of patients undergoing donor nephrectomy at a single tertiary hospital in Sydney, Australia. METHOD: Retrospective capture and analysis of clinical, demographic, and operative data for all living donor nephrectomies performed between 2007 and 2022 at a single University Hospital in Sydney, Australia. RESULTS: Four hundred and seventy-two donor nephrectomies were performed: 471 were laparoscopic, two of which were converted from laparoscopic to open and hand-assisted nephrectomy, respectively, and one (.2%) underwent primary open nephrectomy. The mean warm ischemia time was 2.8 min (±1.3 SD, median 3 min, range 2-8 min) and the mean length of stay (LOS) was 4.1 days (±1.0 SD). The mean renal function on discharge was 103 µmol/L (±23.0 SD). Seventy-seven (16%) patients had a complication with no Clavien Dindo IV or V complications seen. Outcomes demonstrated no impact of donor age, gender, kidney side, relationship to the recipient, vascular complexity; or surgeon experience, on complication rate or LOS. CONCLUSION: Laparoscopic donor nephrectomy is a safe and effective procedure with minimal morbidity and no mortality in this series.

Predicting Features of Visceral Stent Failure in Fenestrated Endovascular Aortic Aneurysm Repair.

PURPOSE: Visceral stents in fenestrated endovascular aortic repair (FEVAR) have a significant risk of complications and carry a considerable burden of reinterventions. The aim of this study is to identify preoperative and intraoperative predictors of visceral stent failure. MATERIALS: A retrospective review of 75 consecutive FEVARs in a single center from 2013 to 2021 was undertaken. Data on mortality, stent failure, and reintervention pertaining to 226 visceral stents were collected. METHODS: Anatomical features including aortic neck angulation, aneurysm diameter, and angulation of target viscerals were obtained from preoperative computed tomography (CT) scans. Stent oversizing and intraprocedural complications were recorded. Postoperative CT scans were analyzed to determine the length of cover of target vessels. RESULTS: Only bridging stents through fenestrations to visceral vessels were considered; 28 (37%) cases had 4 visceral stents, 24 (32%) had 3, 19 (25%) had 2, 4 (5%) had 1. Thirty day mortality was 8%, a third of which was related to visceral stent complications. Intraprocedural complexity was documented during the cannulation of 8 (3.5%) target vessels, with a technical success rate of 98.7%. A significant endoleak or visceral stent failure was identified in 22 stents (9.8%) postoperatively, of which 7 (3%) had in-patient reintervention within 30 days. Further reinterventions at 1, 2, and 3 years were 12 (5.4%), 2 (1%), and 1 (0.4%), respectively. Most reinterventions were for renal stents (n=19, 86%). A smaller stent diameter and a shorter length of visceral stent were significant predictors of failure. No other anatomical feature or stent choice was found to be a significant predictor of failure. CONCLUSIONS: The modality of visceral stent failures varies, but renal stents with a smaller diameter and/or shorter length are more likely to fail over time. Their complications and reinterventions are common and carry a significant burden; therefore, close surveillance must be continued long term. CLINICAL IMPACT: With this work we share the methodology adopted at our centre to treat juxtarenal aneurysm with FEVAR. Thanks to this detailed review of anatomical and technical features we provide guidance for endovascular surgeons to face hostile aneurysm with peculiar visceral vessels anatomy. With our findings will also motivate industries in their attempt to produce improved technologies able to overcome issues identified in this paper.

CD4 T cell-intrinsic role for the T helper 17 signature cytokine IL-17: Effector resistance to immune suppression.

Untoward effector CD4+ T cell responses are kept in check by immune regulatory mechanisms mediated by CD4+ and CD8+ T cells. CD4+ T helper 17 (Th17) cells, characterized by IL-17 production, play important roles in the pathogenesis of autoimmune diseases (such as arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, among others) and in the host response to infection and cancer. Here, we demonstrate that human CD4+ T cells cells exposed to a Th17-differentiating milieu are significantly more resistant to immune suppression by CD8+ T cells compared to control Th0 cells. This resistance is mediated, in part, through the action of IL-17A, IL-17F, and IL-17AF heterodimer through their receptors (IL-17RA and IL-17RC) on CD4+ T cells themselves, but not through their action on CD8+ T cells or APC. We further show that IL-17 can directly act on non-Th17 effector CD4+ T cells to induce suppressive resistance, and this resistance can be reversed by blockade of IL-1ß, IL-6, or STAT3. These studies reveal a role for IL-17 cytokines in mediating CD4-intrinsic immune resistance. The pathways induced in this process may serve as a critical target for future investigation and immunotherapeutic intervention.

A retrospective examination of changes in drinking motives during the early COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has led to substantial changes in college student alcohol use. Changes in drinking motives may explain some of these changes in drinking patterns. The purpose of the present study is to explore how drinking motives and alcohol use have changed amongst college students considering the timeframes before and after the onset of COVID-19 pandemic (i.e., March 2020) in the United States. We hypothesized that there would be significant changes in drinking motives after March 2020, which would be significantly related to changes in alcohol use. METHODS: Participants for the current study were undergraduate students reporting lifetime alcohol use (n = 198, Mage = 21.3, 66.7% female, 86.4% White) recruited through online advertisements in classes to complete an online survey in April 2020. Participants were asked to report on their drinking motives and alcohol use considering the timeframes before and after the onset of closures and stay-at-home orders during the COVID-19 pandemic (i.e., before and since March 2020). RESULTS: Paired samples t-tests revealed that endorsement of social (t[171) = 12.79, p < .001, d = 1.16) and conformity motives significantly decreased (t[170] = 4.46, p < .001, d = 0.31), while endorsement of coping motives significantly increased (t[172] = -2.70, p = .008, d = .15) after the onset of COVID-19. Linear regression analyses, controlling for drinking motives before March 2020, revealed that changes in enhancement (ß = -.47, p < .001) and coping motives (ß = -.22, p = .04) were significantly associated with changes in alcohol use quantity. CONCLUSIONS: Findings of the present study support the need for interventions to target coping and social drinking to reduce risk for alcohol use.

Docosahexaenoic Acid Explains the Unexplained in Visual Transduction.

In George Wald's Nobel Prize acceptance speech for "discoveries concerning the primary physiological and chemical visual processes in the eye", he noted that events after the activation of rhodopsin are too slow to explain visual reception. Photoreceptor membrane phosphoglycerides contain near-saturation amounts of the omega-3 fatty acid docosahexaenoic acid (DHA). The visual response to a photon is a retinal cis-trans isomerization. The trans-state is lower in energy; hence, a quantum of energy is released equivalent to the sum of the photon and cis-trans difference. We hypothesize that DHA traps this energy, and the resulting hyperpolarization extracts the energized electron, which depolarizes the membrane and carries a function of the photon's energy (wavelength) to the brain. There, it contributes to the creation of the vivid images of our world that we see in our consciousness. This proposed revision to the visual process provides an explanation for these previously unresolved issues around the speed of information transfer and the purity of conservation of a photon's wavelength and supports observations of the unique and indispensable role of DHA in the visual process.

Liver splitting during normothermic machine perfusion: a novel method to combine the advantages of both in-situ and ex-vivo techniques.

BACKGROUND: Split liver transplantation permits the transplant of two recipients using a single donor liver. Liver splitting can be performed using the ex-vivo technique (more convenient), or the in-situ technique (shorter cold ischaemic time). We aimed to develop a technique for liver splitting during normothermic machine perfusion which combines the advantages of both techniques and permits graft assessment prior to transplant. METHODS: Human livers declined for transplantation were perfused at 36 °C using a modified-commercial perfusion machine. We developed a six-step method to split whole livers into left lateral segment grafts and extended right grafts. Both partial livers were then perfused on separate machines for individual assessment. RESULTS: Using our technique, 10 whole livers were successfully split during normothermic perfusion resulting in 20 partial grafts. Apart from a single graft which failed due to a technical error, all grafts survived for 24-h after splitting. Survival was demonstrated by lactate clearance, bile production and synthesis of coagulation factors. CONCLUSIONS: Liver splitting during normothermic machine perfusion has the potential to revolutionise split liver transplantation. We describe a novel technique that reliably achieves two grafts from a single donor liver. This raises the possibility of semi-elective transplantation, and sophisticated graft assessment prior to implant.

Turning the Tide on Hepatitis C Virus-Related Liver Transplantation: The Return on Investment in Hepatitis C Virus Treatment in Australia and New Zealand.

Introduction of universal access to direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in Australia and New Zealand on March 1st , 2016, has had a major impact on the number of people with chronic HCV infection, but the impact on liver transplantation rates is unknown. We conducted a retrospective registry study including all adult liver transplantations from the Australia and New Zealand Liver and Intestinal Liver Transplant Registry (ANZLITR) data set. Interrupted time series analysis determined the impact of DAAs in 2016 on the number of HCV liver transplantations per year. Cox regression analysis was used to determine the impact of DAAs on post-liver transplantation survival. Between January 1, 1990, and December 31, 2019 5318 adult liver transplantations were performed, and 29% (1531) were for HCV infection. Prior to the introduction of DAAs, there was a mean increase of 3.5 adult liver transplantations performed for HCV per annum, but between 2016 and 2019 there was a mean decrease of 7.9 adult liver transplantations per annum (P < 0.001). Similarly, the proportion of liver transplantations performed for HCV increased from 9% (1990) to 33% in 2016 and then fell to 23% in 2019 (P < 0.001). The number and proportion of patients with HCV added to the liver transplantation waiting list also fell in 2016 (P < 0.001) when compared with other indications. The introduction of DAAs was associated with a 31% reduction in death after liver transplantation, adjusted for age at transplant and hepatocellular carcinoma (HCC; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.48-0.99; P = 0.047). The number of adult liver transplantations performed for HCV-related liver cirrhosis and HCC has reduced since the introduction of universal access to DAAs in 2016 in Australia and New Zealand.

Inclusion and reporting of sex, gender, and race/ethnicity in randomized controlled trials of nonpharmacological treatments for alcohol use disorder: A meta-epidemiologic review.

Alcohol use disorders (AUDs) are among the most prevalent behavioral and mental health diagnoses. Individuals with an AUD are at increased risk for numerous consequences across their social, health, and psychological functioning. Research suggests that differences may exist in the prevalence and consequences of AUD and in the efficacy of AUD treatment across demographic characteristics (i.e., sex/gender and race/ethnicity). This meta-epidemiologic review examined the inclusion of diverse groups (sex/gender and race/ethnicity) in published randomized controlled trials of nonpharmacological treatments for AUD since 1994, following passage of the National Institutes of Health Revitalization Act of 1993. We systematically searched databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria. The initial search strategy yielded 7931 articles. After excluding ineligible articles, 155 were included in the present review for synthesis. Of the articles included in this review, only 57 (36.8%) fully reported on both their sample's sex/gender and racial/ethnic breakdown. Of the total sample, seven articles specifically examined one racial/ethnic group and 32 specifically examined one sex/gender group. Six articles (3.9%) reported no information regarding the racial/ethnic breakdown of their sample and five articles (3.2%) reported no information regarding the sex/gender breakdown of their participants. Only two articles (1.3%) reported on subgroup analyses that examined differences in treatment outcomes by both sex/gender and race/ethnicity, despite guidelines set forth by NIH. Only 46 articles (29.7%) described the failure to include diverse sex/gender or racial/ethnic groups or concerns about the generalizability of study findings given their sample's sex/gender or racial/ethnic composition as methodological limitations. These results indicate that substantial efforts must be put forth by the scientific community to ensure the inclusion, analysis, and reporting of data focused on women/females and members of minoritized racial/ethnic groups.