Adhesive bonding of copper prepared by laser-interference near the interference structuring limits

Adhesive bonding requires adequate surface preparation for ensuring an appropriate joint quality. The interest in adhesive joining has recently expanded to thermal systems having a large number of joints employed for manufacturing and assembly. This study presents surface topology of copper 110 produced by a laser-interference setup that would theoretically yield a periodicity of 1.7 mm, which is near the 1.6-2 mm structuring limit that was estimated based on thermal diffusion length scale for an 8 ns laser pulse. The results show that although the expected periodic interference structuring was not attained, the melt-induced texturing was affected by the laser-interference profile. Single-lap shear tests are performed with specimen surfaces prepared by traditional abrasion and laser interference structuring methods. Several laser processing parameters, such as the laser spot size, density, number of pulses, and raster speed were studied. Scanning electron microscope and profilometry measurements were used to characterize the processed surface microstructures. Web-like structures, which indicate widespread melting, were shown to be formed at different processing conditions. Based on the surface topologies investigated, two laser raster speeds were selected to make single-lap-joint specimens. Baseline joints were prepared by abrading joining specimens. The shear-lap strength and displacement at maximum load were shown to be higher by 16.8% and 43.8% for the laser-structured specimens than those of the baseline specimens, respectively. Moreover, the load-displacement curves indicate that the laser-structured joints are more ductile than those without laser-structuring. The increase ductility for the laser-structured joints was found to yield an increase in the energy absorbed during shear-lap testing of approximately of 80-90% over those measured for baseline joints. It is another indicator that laser-interference structuring enhanced the bonding performance of single-lap shear joints

Isolation of Phosphatidylethanolamine as a Solitary Cofactor for Prion Formation in the Absence of Nucleic Acids

Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of purified recombinant (rec)PrP substrate into infectious recPrP(Sc) molecules. Other phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol, were unable to facilitate recPrP(Sc) formation in the absence of RNA. PE facilitated the propagation of PrP(Sc) molecules derived from all four different animal species tested including mouse, suggesting that unlike RNA, PE is a promiscuous cofactor for PrP(Sc) formation in vitro. Phospholipase treatment abolished the ability of brain homogenate to reconstitute the propagation of both mouse and hamster PrP(Sc) molecules. Our results identify a single endogenous cofactor able to facilitate the formation of prions from multiple species in the absence of nucleic acids or other polyanions

Incidence and risk factors of delirium in patients post pancreaticoduodenectomy

AbstractBackgroundPost-operative delirium is an important and common complication of major abdominal surgery characterized by acute confusion with fluctuating consciousness. The aim of this study was to establish the incidence of post-operative delirium in patients undergoing a pancreaticoduodenectomy and to determine the risk factors for its development.MethodsFrom a prospectively maintained database, a retrospective cohort analysis was performed of 50 consecutive patients who underwent a pancreaticoduodenectomy at the National Surgical Centre for Pancreatic Cancer in St. Vincent's University Hospital, Dublin and whose entire post-operative stay was in this institution, between July 2011 and December 2012. Two independent medical practitioners assessed all data and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder (DSM), fourth edition. Univariate and multivariate analyses were performed.ResultsSeven patients (14%) developed post-operative delirium. The median onset was on the second post-operative day. Older age was predictive of an increased risk of delirium post-operatively. Those who developed delirium had a significantly increased length of stay (LOS) as well as a significantly increased risk of developing at least a grade 3 complication (Clavien-Dindo classification).ConclusionThis study demonstrates that post-operative delirium is associated with a more complicated recovery after a pancreaticoduodenectomy and that older age is independently predictive of its development. Focused screening may allow targeted preventative strategies to be used in the peri-operative period to reduce complications and costs associated with delirium

Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II) : a protocol for a randomized controlled trial

BACKGROUND: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver. METHODS: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed. DISCUSSION: This RCT will investigate the efficacy of a 12-week multidisciplinary rehabilitation programme for survivors of UGI and HPB cancer compared to standard survivorship care. If effective, ReStOre II will provide an exemplar model of rehabilitation for UGI and HPB cancer survivors. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov, registration number: NCT03958019, date registered: 21/05/2019

Does neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization improve survival in patients undergoing liver transplant for hepatocellular carcinoma?

PURPOSE:We aimed to compare the overall (OS) and disease-free survival (DFS) of patients undergoing orthotopic liver transplant (OLT) for hepatocellular carcinoma who did and did not have neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization (DEB-TACE).METHODS:This is a retrospective study of 94 patients with HCC transplanted between 2000 and 2014 in a single tertiary center. Pre- and postoperative features, DFS and OS were compared between patients who received pre-OLT DEB-TACE (n=34, DEB-TACE group) and those who did not (n=60, non-TACE group). Radiologic and histologic response to neoadjuvant treatment as well as its complications were also studied.RESULTS:There were no significant differences in post-transplantation DFS and OS rates between groups (5-year DFS: 70% in DEB-TACE group vs. 63% in non-TACE group, P = 0.454; 5-year OS: 70% in DEB-TACE group vs. 65% in non-TACE group, P = 0.532). The DEB-TACE group had longer OLT waiting time compared with the non-TACE group (110 vs. 72 days; P = 0.01). On univariate and multivariate analyses, alpha-fetoprotein (AFP) levels >500 ng/mL prior to OLT were associated with decreased OS and DFS regardless of neoadjuvant approach (hazard ratio of 6, P = 0.001 and 5.5, P = 0.002, respectively).CONCLUSION:Patients who underwent neoadjuvant DEB-TACE and OLT for hepatocellular carcinoma had no statistically different OS or DFS at 3 and 5 years from patients undergoing OLT alone

In Situ Photodegradation of Incorporated Polyanion Does Not Alter Prion Infectivity

Single-stranded polyanions ≥40 bases in length facilitate the formation of hamster scrapie prions in vitro, and polyanions co-localize with PrPSc aggregates in vivo [1], [2]. To test the hypothesis that intact polyanionic molecules might serve as a structural backbone essential for maintaining the infectious conformation(s) of PrPSc, we produced synthetic prions using a photocleavable, 100-base oligonucleotide (PC-oligo). In serial Protein Misfolding Cyclic Amplification (sPMCA) reactions using purified PrPC substrate, PC-oligo was incorporated into physical complexes with PrPSc molecules that were resistant to benzonase digestion. Exposure of these nuclease-resistant prion complexes to long wave ultraviolet light (315 nm) induced degradation of PC-oligo into 5 base fragments. Light-induced photolysis of incorporated PC-oligo did not alter the infectivity of in vitro-generated prions, as determined by bioassay in hamsters and brain homogenate sPMCA assays. Neuropathological analysis also revealed no significant differences in the neurotropism of prions containing intact versus degraded PC-oligo. These results show that polyanions >5 bases in length are not required for maintaining the infectious properties of in vitro-generated scrapie prions, and indicate that such properties are maintained either by short polyanion remnants, other co-purified cofactors, or by PrPSc molecules alone

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Obesity in adults: a 2022 adapted clinical practice guideline for Ireland

This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570